Healthy Aging, Longevity and Life Extension

Dear Future Centenarian,

Almost twenty years ago, I bought some furniture from one of the nicest, most gentle men I ever knew. He owned a furniture store in my hometown, Johnstown, PA. That was the first time I met him, even though I went to high school with his son.

He came to my home to ensure delivery went well, and we got into a long conversation. I don’t remember much of the discussion, but a lot of it had to do with aging and how great his life was up to recently. One sentence stuck with me for twenty years and helped shape my future. That sentence was:

“I never thought it would be like this.”

Mr. Gearhart was probably in his 70’s at the time, and he was not aging well. He was afflicted with early-stage Parkinson’s which prompted him to explain to me how aging absolutely sucked. He went on to say he always knew he would grow old, and then he laid that haunting sentence on me. It was a distressing conversation for me and a sad time for his family. I’m sure he’s gone by now, and his death must have been agonizing. He wasn’t one of the “lucky” ones with a squared mortality curve.

A squared mortality curve is where a person stays healthy until he or she dies. Most gerontologists try to square mortality curves to alleviate old age suffering. Most mortality curves decline from birth to death, especially in the later stages of life. That means your health gradually declines as you age, usually severely in the last ten years or so, just like Mr. Gearhart’s. So squaring the curve generally means a quick comfortable death.

A squared curve is not my goal. A horizontal one is. That would be where you stay in top shape with no end in sight. You would see no decline, because you wouldn’t age. (Yes, I know a “horizontal curve” is technically not a curve, but a line. I hardly ever get to coin a term though, so I’m going to keep using it.)

Then, if an accident suddenly ended your life, your curve would then become squared.

If you’re not yet convinced that keeping your mortality curve horizontal is possible, I’m sure you most certainly prefer a squared curve to that of a declining one. Personally, I’m holding out for quality AND quantity.

But whichever your goal is, you will advance toward it by keeping up with the weekly information in Longevity News Digest.

By the way, a horizontal curve is my goal for you as well as for me.

P.S. If you have donated to Maximum Life Foundation and are waiting for your final premiums, your wait is almost over. Stem Cell Products is taking delivery next week of their first inventory of Signals, the breakthrough skin care line. You will be receiving yours soon, and your wait will have been worth it. If you have had a change of address, please let me know.
__________________________________

AVOID CHRONIC INFLAMMATION

Chronic inflammation is a potent source of biochemical damage that contributes to age-related disease. A reminder of the way in which that works and what can be done:

http://www.fightaging.org/archives/001659.php

The best short term way of evading chronic inflammation, and thereby increasing your chances to living more healthy years, is to avoid carrying excess visceral fat. But that only gets you so far: eventually even the healthiest immune system in the healthiest body starts to fall into a permanent condition of chronic inflammation called inflammaging. Evolution didn't produce a system that can be used for as long as we modern humans would like."

So when Reason says 'avoid chronic inflammation' he’s not really talking about sane lifestyle choices, although that's very necessary as well. He really means 'do what you can to help advance medical research into repairing our aged immune systems.' As time goes by, you'll find that the greatest determinant of your health and longevity is medical technology that can repair the damage of aging. While we're healthy and active, we should do what we can to advance that medical research; it'll pay off later.
______________________________

LATEST HEALTHY LIFE EXTENSION HEADLINES

Indy Longevity Mutation Works through Mitochondria (January 23 2009) http://news.brown.edu/pressreleases/2009/01/aging
Another longevity mutation is shown to work by reducing the all-important emission of free radicals from the mitochondria: "first discovered in 2000 [a] mutation in the Indy ('I'm Not Dead Yet') gene [extends] the life span of fruit flies. Subsequent studies of the Indy flies have led to the new finding that a mechanism in those genetically altered fruit flies appears to reduce significantly the production of free radicals, a cellular byproduct that can contribute to the aging process. This intervention takes place with few or no side effects on the quality of life for the fruit fly. The discovery could lead to the development of new anti-aging treatments. There are very few, if any, interventions that are known to dramatically extend healthy lifespan. Understanding how [the] Indy mutation alters the metabolic state of the fruit fly would allow someone to come up with pharmacological interventions that could mimic it and give you the benefit of genetic manipulation without having to do genetics."

Geron Going to Trials with Stem Cell Therapy (January 23 2009) http://www.nytimes.com/2009/01/23/business/23stem.html
As the New York Times reports, Geron's embryonic stem cell therapy for spinal injuries is soon entering phase I human trials. Make what you will of timing, and consider that in the absence of the FDA this would already be in clinics: "The clearance of the clinical trial - of a treatment for spinal cord injury - is to be announced Friday. Geron's trial will involve 8 to 10 people with severe spinal cord injuries. The cells will be injected into the spinal cord at the injury site 7 to 14 days after the injury occurs, because there is evidence the therapy will not work for much older injuries. Geron's therapy involves using various growth factors to turn embryonic stem cells into precursors of neural support cells called oligodendrocytes, which are then injected into the spinal cord at the site of the injury. The hope is that the injected cells will help repair the insulation, known as myelin, around nerve cells, restoring the ability of some nerve cells to carry signals. There is also some hope that growth factors produced by the injected cells will spur damaged nerve cells to regenerate." By way of a reminder, we should all be interested in technologies for myelin repair, given the evidence for a general decline in myelin during aging.

Rebuilding Nerves with Viruses (January 22 2009) http://www.technologyreview.com/biomedicine/21991/
From the Technology Review: "Researchers working on tissue engineering hope to eventually be able to use a patient's own cells to grow replacement tissue for damaged hearts, livers, and nerves. But mimicking the structure and function of the body's tissue has proved difficult. Matrices of supportive, fibrous proteins sustain the cells of the heart, lungs, and other tissues in the body. These scaffolds provide both structural support and chemical signals that enable an organ or nerve tissue to function properly. Viruses that mimic supportive nerve tissue may someday help regenerate injured spinal cords. While other tissue-engineering materials must be synthesized and shaped in the lab, genetically engineered viruses have the advantage of being self-replicating and self-assembling. They can be designed to express cell-friendly proteins on their surfaces and, with a little coaxing, be made into complex tissue like structures. Preliminary studies show that scaffolds made using a type of virus called a bacteriophage (or phage) that infects bacteria but cannot invade animal cells can support the growth and organization of nerve cells."

Beyond Stem Cells (January 21 2009) http://www.agemed.org/default.asp?page=ShaneLaskyBeyondStemCellsJan09
A fascinating article: "stem cells are an imprecise physiological system to directly communicate to cellular networks of a host organism. The future of stem cell research will not necessarily be in the transplantation of stem cells to a specific pathogenic tissue region, but rather in reeducating or reprogramming that particular cellular network. Each organism has an exacting molecular blue print, which as a function of epigenetics, is either enhanced or mollified through its interfacement with a particular environmental milieu. Stem cell transplantation is not a precise strategy for amelioratively reprogramming cellular networks, which are compromised. In most instances, the stem cells, which have been transplanted are only inducing a minimum benefit in terms of their medicinal efficacy. Stem cell transplantation is not a therapeutic pantheon, but rather a way to comprehend how to modify a tissue's proteomics or physiological processes. Clinical medicine in the future will not involve providing imprecise cellular substrates, which vaguely impact genetic transcription and translation or millions of stem cells to a pathophysiologic tissue. Medical therapies will [instead] be a precise utilization of peptides which can ardently reprogram an overall.

Regenerating Stroke Damage (January 19 2009) http://news.bbc.co.uk/2/hi/health/7795586.stm
The BBC looks at a clinical trial for Reneuron's foetal-derived stem cell line: "A Glasgow team is to launch a major trial to assess whether stem cells can be used to treat stroke patients. If it works, as it has done in animal model systems, it may allow new nerve cells to grow or regeneration of existing cells and actual recovery of function in patients who would not otherwise be able to regain function. For the high proportion of patients who make an incomplete recovery [you] can reorganize the brain, you can help that reorganization with physiotherapy but you cannot cause new nerve cells to grow. The hope with stem cell therapy is that by putting in new cells and new tissue that you can further improve on that recovery. We have only taken one donation of tissue to make this product. We have a technology that is able to scale up an individual cell into all of the cells that are required to treat thousands of patients. We think this is a major plus in the technology we have and really negates the ethical concerns about the original use of fetal tissue."

A Look at Osiris Therapeutics (January 19 2009) http://pharmexec.findpharma.com/pharmexec/ArticleStandard/Article/detail/575911?contextCategoryId=47505
An interview with the Osiris Therapeutics president is as revealing of the way in which the FDA constrains progress as it is of the work being done. Broadly promising scientific applications are held back for years and squashed down to minor, narrowly approved uses - and everyone involved has to speak as though this is wonderful and the best of all possible worlds lest they are targeted for retribution. It's a sorry state of affairs. From the interview: mesenchymal stem cells or MSCs "do three things: They downregulate inflammation, they work to regenerate the damaged connective tissue, and they prevent scarring or fibrosis. That's the Holy Trinity of the mesenchymal stem cell. It's the natural progression or sequence of how we respond to injury. When we're young, that process works well. Children heal in miraculous ways. Conversely, an elderly person will die of something like a fractured hip. This is because children have 1,000-fold more MSC in their body than adults do. What happens is an adult ends up with a very exaggerated inflammatory response, a weak regenerative response, and a lot of scarring. We can reverse that trend by administering MSC. Because MSCs naturally have a broad range of things they can respond to, our job is to package them as something that will satisfy the FDA."

Value Reflections

One of the advantages of old age is your increased ability to reflect. You can reflect on the mistakes you made and on your regrets as some people choose to do most of the time. That’s called dwelling. Or, you can briefly reflect on those negative experiences and learn from them. That’s called wisdom.

An even more positive form of reflection is value reflection. No matter whom you are or how you measure your levels of happiness and success, you definitely have created and/or experienced values during your lifetime. Value reflection is one of the most rewarding and pleasurable experiences of life. Who doesn’t like to relive happy memories? Who doesn’t take pride and pleasure in looking back on the positive contributions you made to society, your market, your family, your friends and to yourself?

We all carry within us a treasure of values to be proud of, and with each passing year, that treasure grows, whether you are aware of it or not.

With extended longevity, imagine your possibilities. Not only is technology growth exponential, but so is personal growth. And if you remain vibrant, your enthusiasm can actually intensify with age.

In past issues, I wrote about how the power of technology doubles every year, including the technology that contributes to radical life extension. That means next year will see a doubling of all that power we made since the beginning of history. And here is what that means to you:

If you take the healthy steps to live an extra year, the technology that could lead to your open ended lifespan doubles in that year. If you decide to adopt a lifestyle that adds ten more quality years to your life, life enhancing technology will increase by over 1000 times! And then if you try just a little harder and add another extra year, the power of that technology will double to 2000 times. That means your 11th extra year was just as beneficial to you as those first extra ten.

Then add another year and… well, you get the idea. Before you know it, we will have cracked the longevity code, and you will be on your way to endless youth.

And what could one of the most pleasurable things about that be? As I said, more and more years to add happiness and value and even better value reflection. Imagine what you can accomplish in two lifetimes. In three or more. Imagine how big your values treasure chest will grow as you exponentially acquire wisdom.
____________________________________________

LATEST HEALTHY LIFE EXTENSION HEADLINES

The Life Expectancy Puzzle of Left-Handedness (December 05 2008) http://pmid.us/19044215
Many identified differences in human longevity between groups lack conclusive explanations, such as why women have a greater life expectancy. Differences in life expectancy due to handedness are another puzzle: "Many studies report that left-handers have a shorter longevity than right-handers, and the present study may provide a possible explanation for that finding. In a Cardiac Rehabilitation Unit for the elderly with a mean age of 75.2 years the prevalence of left-handers was 16.7%. This latter value was significantly different from the 6.7% in controls of similar age. These data suggest that heart disease may be one reason for a reduced longevity among left-handers. Left-handers use the right hemisphere for movement, and unilateral activation of that hemisphere in the form of EEG desynchronization and deactivation in the form of EEG slow waves are both related to cardiac abnormalities." In the grand scheme of things these differences are unimportant: the greatest determinant of our future longevity is progress in the application of aging research.

On Immunosenescence (December 05 2008) http://pmid.us/19047800
Researchers discuss the failing, age-damaged immune system: "At present, individuals can live up to 80-120 years, a time much longer than that of our ancestors, as a consequence of the improvements in life conditions and medical care. Thus, the human immune system has to cope with a lifelong and evolutionarily unpredicted exposure to a variety of antigens, which are at the basis of profound age-related changes globally indicated as immunosenescence, a multifaceted phenomenon that increases morbidity and mortality due to infections and age-related pathologies. The major changes occurring during immunosenescence are the result of the accumulation of cellular, molecular defects and involutive phenomena (such as thymic involution) occurring concomitantly to a hyperstimulation of both innate and adaptive immunity (accumulation of expanded clones of memory and effector T cells, shrinkage of the T cell receptor repertoire, progressive activation of macrophages), and resulting in a low-grade, chronic state of inflammation defined as inflammaging. It is unknown whether inflammaging, which represents a risk factor for most age-related pathologies, is a cause or rather an effect of the aging process. Centenarians seem to be equipped with gene variants that allow them to optimize the balance between pro- and anti-inflammatory molecules, and thus to minimize the effects of the lifelong exposure to environmental insults and stressors."

Dormant Emergency Stem Cells (December 04 2008) http://www.eurekalert.org/pub_releases/2008-12/haog-dsc120408.php
An intriguing discovery from a cancer research group that I suspect has more promise for the field of regenerative medicine: "Up to now, scientists have assumed that adult stem cells have a low division rate. According to theory, they thus protect their DNA from mutations. [Researchers] have now discovered a group of stem cells in mouse bone marrow that remain in a kind of dormancy [and] divide only about five times throughout the life of a mouse. Translated to humans, this would correspond to only one cell division in 18 years. In contrast, stem cells of the larger group, the 'active' stem cells, divide continuously about once a month. However, in an emergency such as an injury of the bone marrow or if the messenger substance G-CSF is released, the dormant cell population awakes. Once awakened, it shows the highest potential for self-renewal ever to be observed in stem cells. If transplanted into irradiated mice, these cells replace the destroyed bone marrow and restore the whole [blood] system. It is possible to isolate new dormant stem cells from the transplanted animals and these cells are able to replace bone marrow again – this can be done several times in a row. The situation is different with 'active' stem cells, where bone marrow replacement can successfully be carried out only once."

Evidence Against the Cancer Stem Cell Theory (December 03 2008) http://www.eurekalert.org/pub_releases/2008-12/uom-usp112608.php
It would be good for all of us if the cancer stem cell theory turns out to be true for even a majority of cancer types - as this would mean that a side-effect of stem cell research will be a cure for cancer. Unfortunately, there are good reasons to believe that this will not be the case; nothing in human biochemistry is as simple as we'd like. From EurekAlert!: "the cancer stem-cell model [must] be reassessed because it is based largely on evidence from a laboratory test that is surprisingly flawed when applied to some cancers. I think the cancer stem-cell model will, in the end, hold up for some cancers. But other cancers, like melanoma, probably won't follow a cancer stem-cell model at all. Scientists previously estimated that only one in 1 million melanoma cells has the ability to run wild, exhibiting the kind of unchecked proliferation that leads to new tumors. These aggressive interlopers are the cancer stem cells, according to backers of the model. But after updating and improving the laboratory tests used to detect these aberrant cells, [researchers] determined that at least one-quarter of melanoma cells [have] the ability to form new tumors. The assay on which the field is based misses most of the cancer cells that can proliferate to form tumors. Our data suggest that it's not going to be possible to cure melanoma by targeting a small sub-population of cells."

Senescent Cells and Cancer (December 03 2008) http://dx.doi.org/10.1371/journal.pbio.0060301
One of the consequences of an aging immune system is that it stops removing senescent cells - certainly, senescent cells increase dramatically with age. Here is a look at why that process is likely to increase your cancer risk: "Although 'cellular senescence' can suppress tumor formation from damaged cells by blocking the cell division that underlies cancer growth, it has also been implicated in promoting cancer and other age-related diseases. To understand how this might happen, we measured proteins that senescent human cells secrete into their local environment and found many factors associated with inflammation and cancer development. Senescent cells promote the growth and aggressiveness of nearby precancerous or cancer cells. Our findings support the idea that cellular senescence can be both beneficial, in preventing damaged cells from dividing, and deleterious, by having effects on neighboring cells; this balance of effects is predicted by an evolutionary theory of aging." Senescent cells are a prime target for the same sorts of discerning therapies being developed to kill cancer cells with no side-effects.

Towards Tuning the Immune System (December 02 2008) http://www.sciencedaily.com/releases/2008/11/081130153102.htm
Researchers are making good progress towards control over immune cells, and future goals seems likely to be applicable to the restoration of some function to an age-damaged immune system. Researchers have identified "seven different receptors on T cells that can tamp down immune responses during a prolonged battle with an infectious pathogen or against developing cancer. Chronic over-stimulation of the immune system can lead to poor control of infections and cancer, so the results explain why it is that these key immune cells gradually become 'exhausted' and ineffective over time. We are starting to see a picture emerging of a really tuneable array of inhibitory receptors expressed on T cells. That suggests it may be possible to not only dramatically enhance antiviral or antitumor T cell responses, but also to fine tune which response you want to enhance in order to reverse T cell exhaustion and continue fighting an infection or disease. This presents us with a great clinical opportunity. T cells have a lot of weapons at their disposal to control viral infection and most of them are disarmed when these cells become exhausted. It may be possible to selectively rearm T cells while generally reinvigorating them."

More on Exercise and the Aging Brain (December 01 2008) http://www.eurekalert.org/pub_releases/2008-12/rson-ehp112508.phpIt's well worth remembering that regular exercise brings benefits that no present medical technology can match-and at a fraction of the cost of medicines that do far less. EurekAlert! notes that researchers compared "brain scans of older adults who exercise to brain scans of those who do not. The researchers recruited 12 healthy adults, age 60 to 76. Six of the adults had participated in aerobic exercise for three or more hours per week over the last 10 years, and six exercised less than one hour per week. All of the volunteers underwent MRI to determine cerebral blood flow and MR angiography to depict blood vessels in the brain. Researchers were able to make 3-D models of the blood vessels and examine them for shape and size. They then compared the blood vessel characteristics and how they related to blood flow in both the active and inactive groups. The results showed that the inactive group exhibited fewer small blood vessels in the brain, along with more unpredictable blood flow through the brain. The active adults had more small blood vessels and improved cerebral blood flow. These findings further point out the importance of regular exercise to healthy aging."

Kekich’s Credo

Dear Future Centenarian,

About 21 years ago, I was reflecting on some really dumb mistakes I made in my life and what I could do to keep from repeating them. So I drew on almost all the positive lessons I learned and on all the wisdom of people and mentors whose paths I crossed. The result was personal rules of life encapsulated in 100 credos. I named it Kekich’s Credo” and studied it religiously.

A friend of mine got a copy and published it in his newsletter. Then it spread to another newsletter and so on, and in some circles I became known as “The Credo Guy”.

Last October, Pete Hilgartner, a very bright and fascinating chiropractor, called me to ask permission to publish some of my credos in his newsletter. He went on the say he wanted to write a little essay on each as they pertain to health and well-being. Since then, he did about twenty. From time-to-time, I will share some of Dr. Pete’s gems with you, starting with this one:


1. People will do almost anything to stay in their comfort zones. If you want to accomplish anything, get out of your comfort zone. Strive to increase order and discipline in your life. Discipline usually means doing the opposite of what you feel like doing. The easy roads to discipline are 1) setting deadlines, 2) discovering and doing what you do best and what's important and enjoyable to you and 3) focusing on habits by replacing your bad habits and thought patterns, one-by-one, over time, with good habits and thought patterns.

What health habits (or lack thereof) are you holding on to that are keeping you from your goals?

Are you trying to lose weight? Get strong? Get rid of back pain? Maybe you're ignoring your high blood pressure or triglycerides. "Yumm! that pizza just looks too good! I'll be more disciplined tomorrow..."

Here's a wake up call... NO YOU WON'T!

If you want a different outcome in your life, on any dynamic, you have to DO something different, NOW! The same-ol', same-ol 'is gonna get you the same-ol', same-ol'.

Yes, new habits are tough. They take you out of your comfort zone.

Getting up in the morning to stretch before you do anything else (OK, you can go pee first) is going to be new... but what will you gain? Is the pleasure of what you will gain worth the short term discomfort of doing what you haven't done before? What about giving up the donuts and replacing it with an egg? How about taking a walk instead of watching TV?

Change is actually easy once you decide what it is that you really want and don't let anything stand in the way of making that decision a reality. Excuses are simply a way for you to stay in your comfort zone.

When you hear that little voice in your head start to make excuses or rationalize, shout "STOP! Thank you for sharing...now go away...I choose to _______ (fill in the blank.) I'm DONE with my comfort zone!"

You can certainly stay in that warm bed and not go for that walk you planned. After all you can start tomorrow...

The choice is yours... but so are the results.

How are your choices working for you?


This guy is something else, isn’t he? How’d you like to have someone like Dr. Pete as your personal chiropractor? You can find more about him at www.drshilgartner.com.
____________________________________

LATEST HEALTHY LIFE EXTENSION HEADLINES

The Age of the Cyborg (January 09 2009) http://www.publicaffairs.ubc.ca/ubcreports/2009/09jan08/cyborg.html
The cyborg age is sneaking up on us by way of the tools of tissue engineering and improvements in nanoscale manufacture. Sooner or later most of us will have artificial structures in our bodies - though perhaps not the ones we imagined having when we were young: "With age, the human body wears out. And engineered materials - metals, polymers and ceramics - increasingly help repair or replace injured or destroyed body parts. As we become more sophisticated in our ability to design materials, particularly at the nanoscale, we open all kinds of opportunities for repairing damaged body parts. The potential is really unlimited. Considering the great strides materials engineers are making in developing materials that are readily accepted by the body and that accelerate the process of recovery and healing, the age of the Cyborg seems not so much science fiction as it does science fact - a good thing given the increasing life expectancy and enduring desire to lead active lives."

Most Likely Not Programmed Aging (January 08 2009) http://www.eurekalert.org/pub_releases/2009-01/sumc-sru010509.php
From EurekAlert!: "Two previously identified pathways associated with aging in mice are connected. The finding reinforces what researchers have recently begun to suspect: that the age-related degeneration of tissues [is] an active, deliberate process rather than a gradual failure of tired cells. Derailing or slowing this molecular betrayal, although still far in the future, may enable us to one day tack years onto our lives ... There is a genetic process that has to be on, and enforced, in order for aging to happen. It's possible that those rare individuals who live beyond 100 years have a less-efficient version of this master pathway." I suspect that one reason that theories of programmed aging remain somewhat popular is that the reactions of our cells to a slow stochastic accumulation of biochemical wear and tear do look something like the unfolding of a program. Gene expression steadily changes as the damage mounts. So you see research like this, said to support programmed aging but which could just as well support aging as an accumulation of damage. Researchers are linking changes in gene expression previously noted to be important to aging and longevity, but without evidence of the root cause of these changes, it's premature to declare aging programmed.

Provoking Regeneration (January 08 2009) http://www.eurekalert.org/pub_releases/2009-01/icl-scu010709.php
From EurekAlert!: "When a person has a disease or an injury, the bone marrow mobilizes different types of stem cells to help repair and regenerate tissue. New research [shows] that it may be possible to boost the body's ability to repair itself and speed up repair, by using different new drug combinations to put the bone marrow into a state of 'red alert' and send specific kinds of stem cells into action. In the new study, researchers tricked the bone marrow of healthy mice into releasing two types of adult stem cells - mesenchymal stem cells, which can turn into bone and cartilage and that can also suppress the immune system, and endothelial progenitor cells, which can make blood vessels and therefore have the potential to repair damage in the heart. The researchers were able to choose which groups of stem cells the bone marrow released, by using two different therapies. Ultimately, the researchers hope that their new technique could be used to repair and regenerate tissue, for example when a person has heart disease or a sports injury, by mobilizing the necessary stem cells. The researchers also hope that they could tackle autoimmune diseases such as rheumatoid arthritis, where the body is attacked by its own immune system, by kicking the mesenchymal stem cells into action."

More on Tissue Engineering of Bone Marrow (January 07 2009)
http://www.economist.com/science/tm/displaystory.cfm?story_id=12883495
From the Economist: "tissue engineers have mastered the arts of artificial skin and bladders, and recently they have managed to rig up a windpipe for a patient whose existing one was blocked. But more complicated organs elude them. And simpler ones, too. No one, for instance, has managed to grow bone marrow successfully. At first sight, that is surprising. The soft and squishy marrow inside bones does not look like a highly structured tissue, but apparently it is. That does not matter for transplants. If marrow cells are moved from one bone to another they quickly make themselves at home. But it matters for research. Bone marrow plays an important role in the immune system, and also in bodily rejuvenation. Stem cells that originate within the marrow generate various sorts of infection-fighting blood cells and also help to repair damaged organs. However, many anti-cancer and anti-viral drugs are toxic to marrow. That leaves patients taking them susceptible to disease and premature ageing. Experiments intended to investigate this toxicity using mice have proved unsatisfactory. Nicholas Kotov of the University of Michigan in Ann Arbor and his colleagues have therefore been trying to grow human marrow artificially."

Continued Improvement in iPS Cells (January 07 2009) http://www.eurekalert.org/pub_releases/2009-01/bu-cas010709.php
Researchers continue to rapidly improve the technology of production for induced pluripotent stem (iPS) cells: a "research team has discovered a more efficient way to create [iPS] cells, derived from mouse fibroblasts, by using a single virus vector instead of multiple viruses in the reprogramming process. The result is a powerful laboratory tool and a significant step toward the application of embryonic stem cell-like cells for clinical purposes such as the regeneration of organs damaged by inherited or degenerative diseases. Prior research studies have required multiple retroviral vectors for reprogramming - steps that depended on four different viruses to transfer genes into the cells' DNA - essentially a separate virus for each reprogramming gene. Upon activation these genes convert the cells from their adult, differentiated status to what amounts to an embryonic-like state. However, the high number of genomic integrations - 15 to 20 - that typically occurs when multiple viruses are used for reprogramming, poses a safety risk in humans, as some of these genes [can] cause cancer. The major milestone [was] combining the four vectors into a single 'stem cell cassette' containing all four genes. The cassette (named STEMCCA) [was] able to generate iPS cells more efficiently - 10 times higher than previously reported studies."

More on Skulachev's Research and SkQ1 (January 06 2009) http://pmid.us/19120018
One of the items I'd like to see reasonably settled soon is whether longevity can be reliably engineered by targeting antioxidant compounds to the mitochondria and thereby slowing the accumulation of damaged mitochondria and their contribution to aging. We have good demonstrations that it can, and good demonstrations that it can't. Something interesting is clearly going on (as indicated by mice living significantly longer than they ordinarily would), but the details are still fuzzy. One of the lines of this research I've been following for a while is the work of Skulachev and colleagues in Russia, who seem to have developed an ingested compound called SkQ1 that can perform the mitochondrial targeting trick without the need for gene engineering of the sort employed by Rabinovitch. Here's the latest paper from that group: "Very low (nano- and subnanomolar) concentrations of 10-(6'-plastoquinonyl) decyltriphenylphosphonium (SkQ1) were found to prolong lifespan of [an] insect (Drosophila melanogaster) and a mammal (mouse). The lifespan increase is accompanied by rectangularization of the survival curves (an increase in survival is much larger at early than at late ages) and disappearance of typical traits of senescence or retardation of their development. Data summarized here and in the preceding papers of this series suggest that mitochondria-targeted antioxidant SkQ1 is competent in slowing down execution of an aging program responsible for development of age-related senescence."

Enthusiasm for Regenerating Teeth (January 06 2009) http://seattletimes.nwsource.com/html/nationworld/2008593860_teeth06.html
From the Seattle Times: "the real news about the future of dentures is that there isn't much of one. It turns out wisdom teeth are prolific sources of adult stem cells needed to grow new teeth for you. From scratch. In your adult life, as you need them. In the near future. Regenerating a whole tooth is no less complicated than rebuilding a whole heart. Not only do you have to create smart tissue (nerves), strong tissue (ligaments) and soft tissue (pulp), you've got to build enamel - by far the hardest structural element in the body. And you have to have openings for blood vessels and nerves. And you have to make the whole thing stick together. And you have to anchor it in bone. And then you have to make the entire arrangement last a lifetime in the juicy stew of bacteria that is your mouth. It's a nuisance, but researchers are closing in on it. They think the tooth probably will be the first complex organ to be completely regenerated from stem cells. In part, this is because teeth are easily accessible. Nobody is predicting when the first whole tooth will be grown in a human, although five to 10 years is a common guess."

An Interview with Jason Silva (January 05 2009) http://www.bravenewtraveler.com/2009/01/05/interview-jason-silva-on-how-science-will-make-you-live-forever/An interesting interview: "I believe humans have always overcome their biological limitations. It is what has brought us out of the caves and onto the moon. We have cured ourselves of diseases, we fly remarkable machines through the air at 500 miles per hour. We communicate instantly and wirelessly across the world. Why is it such a stretch to imagine us re-programming our biochemistry (much like computer software) so that we may alleviate suffering, decay, and death? Death is a profound tragedy. Human consciousness is basically a profound (and valuable) pattern of information residing in a complex biological machine. This machine can repair itself for a certain period, but over time it wears out and decays at a faster rate than it can fix itself. This is why we die. Today, however, we are at the verge of correcting this. Death is the loss of everything that matters - It is our memories, our loves, the images and dreams that define us - the songs that moved us and the films that shaped us. Death takes this all away. I argue that in the same way we feel compelled to preserve the works of Shakespeare and other great works of art, why shouldn't we extend this into our physicality?"

A Valuable Lesson

As promised, I’m going to pass on a valuable lesson from Dr. Pete Hilgartner.

What is your first reaction to a crisis? Let’s say you get diagnosed with a serious illness. First your heart skips a beat and then thunders like a jackhammer. Maybe you break out in a cold sweat. Then when reality sets in, do you retreat? Do you roll up in a fetal position, pull the covers over your head and hope your problems disappear? Do you tend to sleep more, head for the liquor cabinet or pray harder than you had in years?

How about when you life’s savings gets wiped out overnight due to mismanagement, theft, the economy or just by hard luck?

Or what do you do when the economy slows down, and your customers’ orders slow to a trickle, or you get laid off?

What about when all the real estate equity you built over the years vanishes overnight?

Time to retreat, right? Batten down the hatches. Cut expenses. Downsize. Deprive yourself until things get better. That’s what most people do, and that’s one reason the press tells you our economy sucks.

What if there was a better way to handle crises? Well there is. In fact there are two. The first is offered up by Dr. Pete. The second by yours truly.

Dr. Pete is a fascinating guy and a successful student of life. He was very sickly as a child, way sicker than most people could tolerate. But his illnesses motivated him to set lofty goals. He decided to win an Olympic gold metal, to become an officer in the Marine Corps and to become a physician. He was well on his way to a shot at the gold when his aching back tripped him up. So he joined the Marines and later became a successful physician.

The Marines taught him one of life’s great lessons. They taught him how to survive an ambush.

Capt. Pete survived six ambushes in fact. He realized he survived them the same way he survived his childhood injuries and the same way he’s surviving today’s economic climate. When you’re ambushed, the Marines teach you to head for an escape route. But what is there is none? What do you do when the enemy closes off all escape? Then you make yourself as small a target as possible, right? Wrong!

If you want to escape, to survive, you do the counter-intuitive. You do the unexpected. You expand… and attack. But don’t just sort of expand. Expand with decisiveness, purpose, order and with a plan. Play offense instead of defense. Overcome your fear and take the fight to the enemy. Dr. Pete and most of the company he commanded live today because of that one critical lesson.

Have you noticed that when people are filled with fear, they tend to withdraw? They stop communicating. If they do communicate, it’s usually to complain about how bad things are. When you’re down, be a beacon of optimism. Take charge of your situation. Every cell in your body will react and rally you to your recovery.

Can you force yourself to expand, when every fiber of your existence wants to do what everyone else is doing; succumbing and contracting to fear? Yes, you can!

I have another way to not only survive, but to prosper as well. It’s your surest path to sound health and longevity. In a word, it’s “prevention”. Expand now, and avoid your ambushes. Head off disease and illness by taking precautionary measures now and forever.

It’s a well-known fact that people will go to the ends of the earth searching for cures but will ignore preventative measures. Terminal diseases and what is happening now are concretes. The threat of disease and the future are abstracts. So we live for the moment while internal time bombs tick away. Sooner or later, one catches up with you. And more often than not, it’s too late. If you catch it early enough and/or expand and attack, you have a chance to beat it back. But not all of Capt. Pete’s soldiers got out alive.

Will tomorrow’s technologies obsolete death from aging and other diseases? I’m certain of it. Will we all live to see the day? Unfortunately, no. And most of those who miss the extreme longevity boat will miss it because of inattention to prevention. Some will make it because they will expand when their crisis catches up with them. But with so much at stake, why roll the dice? Play to win, not to not lose. Expand right now, before it’s too late.

Now getting back to reacting to a health crisis. I’m afraid I have some terrible news for you. You have a terminal disease that no one has ever survived. You were born with it, and you too will die from it – unless you improve your odds by expanding and by preventing. It’s called aging. Instead of complaining about it, or even joking about it, for the first time in history, you can actually do something about it. One contribution many of us can make is supporting the research that will conquer the effects of aging while you are still alive. The other is simply taking a proactive approach to your health to keep yourself alive until emerging medical miracles will give you a new lease on life.
________________________________

LATEST HEALTHY LIFE EXTENSION HEADLINES

The Most Important Research (November 07 2008) http://www.exchangemagazine.com/morningpost/2008/week45/Friday/1107018.htm
From the Exchange Morning Post, a statist, public funding viewpoint on longevity science: "Learning how to turn back time - or at least how to slow the aging process - may be more important for improving our overall health than the discovery of a cure for cancer. There are real, tangible benefits, for society as well as individuals, to slowing down the aging process. 'By extending the life span, people would remain in the workforce longer, personal income and savings would increase, age entitlement programs would face less pressure from shifting demographics, and national economies would flourish'. Almost half of the current population over 75 years old is limited in their activity by chronic conditions, with costs to society set to rise dramatically. Given the current predicament we face, we can't ignore the call to tackle aging more aggressively. To those who ask: 'Can we really afford to invest more in such research?' we can reply: 'Can we really afford not to tackle aging?' The greatest obstacle will be convincing the general public that slowing the aging process is both feasible and deserving of a larger share of the funds available for scientific research."

An Overview of Cryonics (November 07 2008) http://kn.theiet.org/magazine/issues/0819/science-without-deadline.cfm
A good article on cryonics from Engineering and Technology: "The field of cryonics, which made its debut in the 1960s, continues to push the envelope and search for a solution to death. The process consists of preserving legally dead humans or pets at very low temperature (below -130C) in the hope that future science can restore them to life, youth, and health. The advancement of medicine and science is so much faster than it used to be. Science fiction is becoming science fact on a daily basis. All of a sudden, cryonics doesn't look quite so far-fetched. Most cryonicists believe reanimations will occur within 50 to 100 years for those currently being cryopreserved. Within that time frame, virtually all current diseases should be curable and elderly people can probably be rejuvenated to a youthful condition. With full disclosures and signed consent, [cryonics] is highly ethical. When you think about the grand scheme of things, cryonics is a lot more conservative than burial or conventional cremation. Tissue preserved at the temperature of liquid nitrogen does not deteriorate, even after centuries of storage. Therefore, if current medical technology can’t keep us alive, we can instead choose to be preserved in liquid nitrogen, with the expectation that future medical technology should be able to reverse any cryopreservation injury and restore good health.

Cells as Vectors for Targeted Therapies (November 06 2008) http://www.eurekalert.org/pub_releases/2008-11/miot-mct110508.php
The possibilities of bioengineering are endless, and one of the most energetic branches of the research community is involved in developing methods of precisely targeting therapies: "MIT engineers have outfitted cells with tiny 'backpacks' that could allow them to deliver chemotherapy agents, diagnose tumors or become building blocks for tissue engineering. The polymer backpacks allow researchers to use cells to ferry tiny cargoes and manipulate their movements using magnetic fields. Since each patch covers only a small portion of the cell surface, it does not interfere with the cell's normal functions or prevent it from interacting with the external environment. Researchers worked with B and T cells, two types of immune cells that can home to various tissues in the body, including tumors, infection sites, and lymphoid tissues - a trait that could be exploited to achieve targeted drug or vaccine delivery. The researchers found that T cells with backpacks were able to perform their normal functions, including migrating across a surface, just as they would without anything attached. By loading the backpacks with magnetic nanoparticles, the researchers can control the cells' movement with a magnetic field."

Towards a Rejuvenated Thymus (November 06 2008) http://www.uga.edu/news/artman/publish/081106_Manley_Research.shtml
One approach to the issue of declining naive T-cells with age - and consequence failure of the immune system - is to boost production by manipulating the thymus: "a key gene may be crucial to maintaining the production of the thymus and its disease-fighting T-cells after an animal's birth. The discovery could help scientists find out how to turn the thymus back on so it could produce T-cells long after it normally shuts down most of its function, which, for humans, occurs by early adulthood. If the finding leads to further ways to manipulate the gene, the result could be a new avenue for the body to fight disease more effectively as the body ages. Such things as infectious diseases, inflammation and heart problems are all related to immune response. You don't have to think far to see how understanding the effect of this gene could affect the quality of life for older people and others as well. If [physicians] were able selectively to turn T-cell production back on, then many diseases that currently afflict older people could become manageable if not, in cases, entirely absent."

Boosting the Aging Immune System (November 05 2008) http://pmid.us/18981163
Many research groups are working on ways to boost the effectiveness of an exhausted immune system - due to either chronic viral infection or aging - without necessarily aiming to address the root causes: "In contrast to most normal somatic cells, which show little or no telomerase activity, immune cells up-regulate telomerase in concert with activation. Nevertheless, during aging and chronic HIV-1 infection, there are high proportions of dysfunctional [immune cells] with short telomeres. Exposure of CD8(+) T lymphocytes from HIV-infected human donors to a small molecule telomerase activator (TAT2) modestly retards telomere shortening, increases proliferative potential, and, importantly, enhances cytokine/chemokine production and antiviral activity. The enhanced antiviral effects were abrogated in the presence of a potent and specific telomerase inhibitor, suggesting that TAT2 acts primarily through telomerase activation. Our study is the first to use a pharmacological telomerase-based approach to enhance immune function."

Incremental Improvements in Scaffolding (November 03 2008) http://www.technologyreview.com/printer_friendly_article.aspx?id=21625&channel=biomedicine&section=
From the MIT Technology Review: "Engineering heart tissue presents particularly tough problems for researchers, since the heart is an active organ. Scaffolds designed for other kinds of tissues did not have the right mechanical properties for heart tissue. Heart tissue must be flexible enough to change shape as the heart contracts, but also strong enough to withstand the intense forces generated by these contractions. The researchers designed the scaffold to encourage cells to align themselves in the same direction to better mimic this property of natural heart muscle tissue. Using a laser cutting technique, they created a pattern of oblong holes in the polymer; the result is a flexible, honeycomb-like structure that is stiffer in one direction than another. Just as rowers line up in one direction to propel a boat forward, 'all the heart muscle cells in a given region have to be lined up and contracting in the same direction' in order for the heart to beat efficiently. The honeycomb-like scaffold [represents] a 'substantial jump' toward that goal. If we had a biodegradable biomaterial, which had beating heart cells, we might be able to return function to [damaged parts] of the heart."

A General Interest Calorie Restriction Article (November 03 2008) http://afp.google.com/article/ALeqM5i8eh2v_zPiht03CZWKvVulsaPYqAAs the science advances, these articles get more positive. Recall the ridicule heaped upon the practice of calorie restriction even just a few years ago. "Some people are doing it strictly to enhance longevity. Others do it to avoid age-related disease, or because they already have diabetes, high cholesterol or clogged arteries and want to clean up their bodies by using diet. In rich countries, 90 percent of the population probably eats, on average, about 50 percent too much. Even if they were to reduce their calorie intake by half, they would still only be at baseline. A wealth of scientific evidence has confirmed that maintaining that balance helps prevent type-2 diabetes, cardiovascular disease and cancer. But experiments with both animals and humans have also shown that pushing one's calorie intake 10 to 20 percent below that baseline threshold -- without lowering nutrients -- may provide additional health advantages. Will this add 10 years to your life? Nobody knows. But one thing is sure -- calorie restriction will help you reach your maximum lifespan potential, which is different for all of us depending on our genetic profile."

A Jobe Kind of Year

Dear Future Centenarian,

It’s been a Jobe kind of year so far. Let me count the ways:

We launched a market trading technology that took 12 years to develop that was designed to raise hundreds of millions of dollars for life extension research. Good news, right? Wrong! We launched it on the exact day the markets fell apart. A bunch of money vanished, and critical life extending projects are on hold..
I hired a contractor to build a real estate project. He promised a 10 month delivery date. Here it is, over three years later, and still not quite done. Meanwhile, the bottom fell out of the market this year, and poof, a couple of million plus – up in smoke.
The same contractor got into a dispute with a sub contractor, who put a lien on the property since the contractor won’t pay. Legal fees and headaches all last week. He cost me hundreds of hours wasted on a project that was supposed to be turnkey.
Father Time stole another year from me.
A borrower defaulted on a big loan.
Verizon inadvertently disconnected my Internet service 17 days ago… and it took 15 of those days to get me back online. When I checked to see why, they inactivated my account instead of reconnecting it. Almost four hours spent on phone calls with about a dozen different representatives. Sound familiar?
There is a situation as bad as #2 that I don’t even want to talk about.
There’s another as bad as #7.
A funder for a key longevity technology was not able to perform on his commitment. Meanwhile, the markets hit the skids, and now it will be 10 times harder to get funding. I believe thousands of lives may ultimately terminate as a result, and a small fortune is jeopardized.
My electric bed took on a mind of its own. From time-to-time, without any warning, the head and foot rise in unison, trapping me in a wedge. The last time it happened, the head inclined just fast enough to barely keep me from reaching the remote. The more I stretched, the farther out-of-reach it got. I had to get rescued. A little joke on Dave.
The final straw. My Vita-Mix (my most important health drink tool) gave out yesterday J.

You might be wondering why I’m sharing my tales of woe with you. Sure, I know, you have your own challenges to cope with. Once again, all this has something to do with your health and longevity.

I’m one of those guys you might hate running into when you are troubled. Instead of getting sympathy, you’ll get an irritating dose of sunshine and a pep talk, just when you wanted someone to share your misery with. Well, I should say, I’m usually that optimistic guy. I have to admit that numbers 1-11 above started consuming my thoughts. And that’s bad. It’s bad because it’s extremely unhealthy, life-shortening and counterproductive… and because I know better.

Do you know your thoughts affect every single cell in your body? Positive, loving grateful thoughts keep you healthy and make you live longer. Negative thoughts destroy you from the inside out. What happens to you usually doesn’t matter one bit. How you react means everything. A new friend reminded me of this in a very interesting way. His name is Dr. Pete Hilgartner, and I’m going to share his words of wisdom with you next week.

I don’t care what your situation is. You have plenty to be grateful for. I know I do. I have lots of positive things and people in my life. I’ve been fortunate enough to have attracted better friends, partners and relationships than most could ever hope for. I also lucked out in the health department. And get this. Just yesterday, a close friend and associate told me a benefactor pledged enough funding to finish developing a technology which may allow you and me to actually live as long as we want someday.

Then there are the little things I tend to take for granted. I started yesterday with a nutritious, delicious breakfast and ended it with a fabulous dinner. I live in one of the best climates in the world. I have a warm comfortable bed, even though it attacks me once in a while. My shoes fit. I have shoes. I have feet! And I have a couple of pages of more things to be grateful for. Just writing this makes me feel a lot better, because when you think a grateful, happy or loving thought, there’s no room in your mind for anything else. So happiness is simply deciding what you want to dwell on. And happiness equates to healthfulness. Sure, you have to face your problems, health and otherwise. But when you do, think of solutions rather than dwelling on the negatives.
___________________________________________

LATEST HEALTHY LIFE EXTENSION HEADLINES

Unregulated Prices Fall, While Quality Improves (October 31 2008) http://www.lef.org/magazine/mag2008/sep2008_Would-You-Tolerate-This-Abuse_01.htm
A piece from the LEF Magazine that makes the points about modern medical research that most people don't think about: "the public today tolerates federal and state laws that enable pharmaceutical companies to conduct business as a virtual monopoly. The result is that Americans pay outlandish prices for mediocre drugs that are often laden with side effects. Unlike regulated prescription drugs, the cost of dietary supplements has plummeted over the past three decades. In a free market environment, technological breakthroughs that occurred in telecommunications will also happen in medicine. More frightening is the suffocating effect that regulation has on the discovery of life-saving therapies. Just imagine if advancement in clinical medicine progressed at the same rapid rate as telecommunications. If it did, we would probably have cures for most killer diseases today!" Heavily regulated markets are bloated, slow markets, in which the incentives are so set as to discourage progress. Present regulation is a very real threat to the future of your health and longevity.

Incremental Improvements in Stem Cell Therapy (October 31 2008) http://www.eurekalert.org/pub_releases/2008-10/hms-scp102908.php
Researchers continue to find ways to alter stem cells to produce better therapies: "Adult stem cells resemble couch potatoes if they hang out and divide in a dish for too long. They get fat and lose key surface proteins, which interferes with their movement and reduces their therapeutic potential. Now, via a simple chemical procedure, researchers have found a way to get these cells off the couch and over to their therapeutic target. To do this, they simply added a molecule called SLeX to the surface of the cells. The procedure took just 45 minutes and restored an important biological function. Delivery remains one of the biggest hurdles to stem cell therapy. The blood stream offers a natural delivery vehicle, but stem cells don't move through blood vessels normally after being expanded in culture. Our procedure promises to overcome this obstacle. Karp cautions that his lab's discovery must be validated in animals, before doctors can apply it in the clinic. He's collaborating with another lab to test the homing ability of the SLeX-dotted cells in mice."

A Little More on IGF-1 and Growth Hormone (October 30 2008) http://dx.doi.org/10.1371/journal.pbio.0060254
Following up on a recent Fight Aging! post, more on the role of IGF-1 in longevity: "Using a mouse model relevant for humans, we showed that lifespan can be significantly extended by reducing the signaling selectively of a protein called IGF-I in the central nervous system. This caused growth retardation, smaller adult size, and metabolic alterations, and led to delayed mortality and longer mean lifespan. Thus, early changes in neuroendocrine development can durably modify the life trajectory in mammals. The underlying mechanism appears to be an adaptive plasticity of somatotropic functions allowing individuals to decelerate growth and preserve resources, and thereby improve fitness in challenging environments. Continuously low IGF-I and low growth hormone levels favor extended lifespan and postpone age-related mortality. Our results further challenge the view that administration of GH can prevent, or even counteract human aging. This knowledge is important since growth hormone is often prescribed to elderly people in an attempt to compensate the unwanted effects of aging."

Ouroboros on Mitochondrial Uncouplers (October 30 2008) http://ouroboros.wordpress.com/2008/10/30/mitochondrial-uncouplers-mimic-the-effects-of-calorie-restriction/
From Ouroboros: researchers "suggest that mitochondrial uncoupling is an effective mimic of [calorie restriction (CR)]. In mitochondria, the electron transport chain uses electrons from glucose and lipids to pump protons across a membrane. This proton gradient can be used to make energy in the form of ATP through oxidative phosphorylation. The process is kind of like generating hydropower. Uncouplers work by putting a leak in the dam, which lets water through without going to the generator. They 'uncouple' the electron transport chain from oxidative phosphorylation, thus reducing the efficiency of energy production. Although animals have uncoupling proteins (these proteins are important for thermogenesis, especially during hibernation), so far there are no known agonists. The researchers instead used low doses of the mitochondria uncoupler DNP.
The DNP treated mice ate the same amount of food as control mice but had lower body mass [and] showed many phenotypes observed in calorie restricted mice. Like CR mice, DNP treated mice had higher rates of respiration with lower production of ROS. Most importantly, DNP treated mice showed an extended lifespan. This study suggests that mitochondrial uncouplers are an effective mimic of calorie restriction and might be a realistic therapeutic intervention for delaying aging and extending lifespan."

Lipids and Alzheimer's (October 28 2008) http://www.medicalnewstoday.com/articles/126012.php
The brain is complex organ, and Alzheimer's is a complex disease: a wide range of strategies produce results that look promising while not addressing the root cause. Indeed, distinguishing symptoms from root causes in Alzheimer's is still an ongoing concern. Here is a potential strategy I have not seen mentioned before: "scientists working with laboratory mice have discovered that complete or partial removal of an enzyme that regulates fatty acid levels lessened the memory and learning deficits of Alzheimer's. The most striking change we discovered in the Alzheimer mice was an increase in arachidonic acid and related metabolites in the hippocampus, a memory center that is affected early and severely by Alzheimer's disease. An enzyme called group IVA phospholipase A2 (or PLA2) released arachidonic acid [in] the brain. Removal or even partial reduction of PLA2 prevented memory and learning deficits and other behavioral abnormalities in the Alzheimer mice." It is worth noting that PLA2 is upstream in biochemical signaling processes that lead to inflammation - I suspect this has more to do with inflammation than fatty acids per se.

Save for the Future

What a week!

If you are in any market, you probably got slaughtered last week. If you didn’t, I want you to handle my investments.

Although I attribute most of the sudden losses to panic selling, it’s still very sobering. We’ll see lots of ripple effects that could last for a long time. We’ll also see more controls which will lead to more erosion of your freedoms.

Meanwhile, I’m working on keeping you alive for a long time, so if the markets are stressing you out, relax and review my previous commentaries on stress.

But this market made one more thing crystal clear to me. You may need money, if you want to dodge the grim reaper. Lots of it. If you didn’t lose money last week, it might be because you don’t have any to lose. And yes, that could be bad if you want to live for an extremely long time.

Let’s face it… the first people who are going to get effective life-extending treatment are those who will be able to afford it. If you’re old and broke when the longevity boat arrives, you might miss it. Sure, prices will come down, and pretty rapidly too. But many of us are on the bubble as it is, and not being near the front of the line could just cost you your life. So what are you going to do about it?

All your life, you have been told to save for the future, and you’re most certainly familiar with the magic of compound interest. As we age, we may regret not starting to save years ago. Now, many people who didn’t save figure it’s too late to amass any kind of fortune, so they live day-to-day, paycheck-to-paycheck. But what if you knew beyond a shadow of a doubt, you would be biologically transformed into a 25-year old, twenty or thirty years from now, if you had $500,000 in the bank at that time. Do you realize that if you socked away about $30,000 in a segregated investment account that compounded at around 10% growth per year, you would have your $500,000 in less than thirty years? (10% is roughly the historical annual growth of the stock market.)

In other words, $30,000 could be the difference between your being part of the last generation to die from aging or part of the first to live endlessly. What if you don’t have $30,000? That’s easy. Save $3,000 now and $3,000 every year in the same type of account, and presto! You’ll have your magical $500,000 in less than thirty years.

I have no idea what full rejuvenation will cost when it’s available, so plan for more, not less. Wouldn’t it be nice to be young again with a pile of money in the bank?
_________________________________

LONGEVITY AND THE COMPOSITION OF MITOCHONDRIA

Comparisons of mitochondrial biochemistry between species of differing innate longevity is one several branches of research to demonstrate the importance of our mitochondria to aging:

http://www.fightaging.org/archives/001584.php

"Mitochondria, the power plants of your cells, generate damaging reactive oxygen species (ROS) in the course of their operation: ROS will race off to damage the first thing they can find by reacting with it, such as a cell membrane. Mitochondria themselves have membranes, and are first in line to be damaged by the ROS they generate. Eventually damage accumulates and cascades to change the surrounding cellular environment very much for the worse. This process is an important root cause of degenerative aging."

This process is why those species more resistant to the damaging effects of reactive oxygen species live longer than their peers. "Resistance" here means that the membranes of mitochondria and other cellular components are built of tougher stuff: proteins less likely to be succumb to ROS attack. Even in primates, mitochondrial composition differences are significant between species and highly correlated with longevity. This all reinforces just how central our mitochondria are to aging, and how vital it is to speed research into repairing damaged mitochondria in humans:

http://www.fightaging.org/archives/001395.php
______________________________

LATEST HEALTHY LIFE EXTENSION HEADLINES

Update on Viruses Versus Cancer (October 10 2008) http://www.sciencedaily.com/releases/2008/10/081008151320.htm
A number of groups are presently working on ways to use viruses to precisely target and kill cancer cells. Here's an update on one of them from ScienceDaily: "The Senecavirus [is] harmless to normal human cells, but could infect certain solid tumors, such as small cell lung cancer, the most common form of lung cancer. Scientists at Neotropix say that, in laboratory and animal studies, the virus demonstrates cancer-killing specificity that is 10,000 times higher than that seen in traditional chemotherapeutics, with no overt toxicity. The company has developed the 'oncolytic' virus as an anti-cancer agent and is already conducting early phase clinical trials in patients with lung cancer. Researchers went on to identify several areas on the viral protein coat that they think might hook onto receptors on cancer cells in the process of infecting them. It will be critically important to find out what region of its structure the virus is using to bind to tumor cells, and what those cancer cell receptors are. Then we can, hopefully, improve Senecavirus enough to become a potent agent that can be used with many different cancers."

Cuervo On Autophagy (October 10 2008) http://websites.afar.org/site/PageServer?pagename=IA_spotlight_main
A piece from earlier this year at InfoAging: "Aging is characterized primarily by the decline of function in various cellular and molecular systems in the body. These changes are influenced by three factors:
genetics, metabolism, and the environment. The focus in Dr. Cuervo's lab is the metabolic changes and resulting damage from these changes that are experienced with age, specifically damage to proteins. Every person experiences this damage to some degree, regardless of their age, but when it comes to repairing or removing the damage, the difference between young and old is clear. In younger people, the damaged or misfolded proteins can be repaired by what are known as chaperone proteins. Yet, like an old car, proteins that have undergone too much repair are not worth maintaining and so they are transported by the chaperone to the lysosome as 'trash' where they bind to a receptor and undergo autophagy (literally, self-eating) inside the organelle. Dr. Cuervo's research focuses on this pathway and how a major decline in its functionality is seen in older organisms." The piece goes on to describe how researchers restored this functionality to youthful levels in aged mice.

A Good Example of a Cell Signaling Application (October 09 2008) http://www.xconomy.com/boston/2008/10/09/provasculon-a-biogen-backed-startup-testing-regenerative-medicine-on-hearts/
An important field resulting from stem cell research is the discovery and application of biochemical signals to direct existing stem cells in the body - they can be made to repair damage where they would ordinarily remain inactive. Only where stem cells themselves are damaged would new cells be needed: in most situations, greater control over the cells you have is good enough. Via Xconomy: "Provasculon is tackling one of the bigger ideas in regenerative medicine - how to stimulate growth of new blood vessels after they've been damaged by a heart attack. Iin rat studies that a novel protein was able to stimulate a certain type of stem cells (better known to scientists as endothelial progenitor cells) to migrate to damaged heart tissue, promote growth of new blood vessels, and ultimately help the heart pump better after a heart attack. The trick here is that Provasculon is trying to make a genetically engineered form of the key protein, SDF-1, that is able to avoid certain enzymes in the body that would like to chop the protein up and render it useless."

All Problems Are a Matter of Atoms (October 08 2008) http://www.acceleratingfuture.com/michael/blog/2008/10/physical-basis-for-problems/
The ultimate goal of medicine is to be able to reliably and precisely manipulate any the molecules in our bodies: all disease, all aging, is a matter of the wrong molecules being in the wrong place at the wrong time. From Accelerating Future: "It's important to realize the obvious: that every human problem, every malady, every concern, every evil, is at root simply a suboptimal arrangement of atoms and molecules. If this sounds quasi-spiritual, it's because it is - for millennia, pre-scientific humans have attributed all ills to various agents - the gods, magicians, and other humans. This is because these ills demand an explanation, and we didn't have a plausible one, so we made it up. Now, at least in the abstract, we have a concrete, very likely correct answer: suboptimal atomic arrangements. This realization is neither trivial nor too broad to be useless. If your problems are caused by the gods (that some people sadly still believe in...), then to solve them, you either need to give up, on engage in rituals [that] have an empirical impact of precisely zero." There is a simple criteria by which to judge whether new technologies will enable better medicine: do they give us the ability to more precisely and easily move atoms around? Modern biotechnology and the molecular manufacturing that will follow are both good examples.

Pondering Aging Stem Cells in the Gut (October 08 2008) http://www.sciencenews.org/view/generic/id/37382/title/Old_age_causes_problems_for_gut_cells
From Science News: "Old age can hit animals in the gut. That's where elderly fruit flies experience a signaling imbalance that disrupts renewal of the gut wall, new research shows. The discovery could help scientists understand why the body's organs malfunction in old age, and why intestinal cancer is so common among older people. Normally, 'adult' stem cells in the intestinal wall churn out a steady stream of new cells to replenish the lining [but] in older animals, this balance seems to be breaking down. The imbalance appears to be triggered by stress - not psychological stress, but the chemical stresses put on cells by free radicals or by chronic inflammation, both of which get worse as an animal ages. Cells in the gut lining respond to this stress by activating a protective gene [which] is part of a signaling pathway that spurs intestinal stem cells to grow and divide. In response, another signaling pathway - called the Delta/Notch pathway - ramps up to try to keep that growth in check. But too much Delta/Notch can also derail the natural conversion of these stem cells into mature gut cells, causing an abnormal accumulation of halfway converted cells. [This] malfunctioning of adult stem cells in old age [is] very similar to what happens in certain human stem cell populations."

Attacking Macrophages in Fat (October 07 2008) http://www.eurekalert.org/pub_releases/2008-10/cp-ki093008.phpYou might recall that the reason excess fat tissue is so damaging seems to be due to roaming macrophages that release inflammatory biochemicals. Via EurekAlert!, a demonstration that reinforces this point: "Over the past decade, it has become quite clear that obesity gives rise to a state of chronic, low-grade inflammation that contributes to insulin resistance and type 2 diabetes [researchers] recently found that a specific subset of macrophages invades obese fat and muscle tissue. Although little was known about them, those macrophages are defined by a CD11c marker expressed on their surfaces. They also produce high levels of proinflammatory chemicals that are linked to the development of obesity-associated insulin resistance. We used a genetic 'trick' that allowed us to rapidly kill these macrophages. The treatment killed these cells within hours, and insulin resistance simply reversed itself. It argues strongly that macrophages are causative for the inflammation that leads to diabetes [in those who are obese]. The most interesting thing is that this reversal occurs very rapidly. Twenty-four hours later the animals' insulin response had completely normalized. They were still obese, but no longer insulin resistant."

Nanofactory Collaboration Colleague Awarded $3 Million

Dear Future Centenarian,

Are you plagued with information overload? It gets worse every day, doesn’t it? If it weren’t for Reason at www.longevitymeme.org, I’d never have the time to sort through all the daily longevity news that you see in this letter. He does a terrific job, I distill it down and slightly edit it, and presto, you spend a few minutes every week to pick and choose whatever hits your hot button. There’s something for almost everybody in each issue, maybe even some life-saving info for you or a loved one.

Here is an excerpt from a release that I got from another source. An article like this might not catch your attention. On the surface, it looks like just another narrow-niche, hi-tech article aimed toward a limited audience. In reality though, it could hold the key to your full age-reversal plus open-ended youth in a super-human body. I’ll tell you why in a moment.
Nanofactory Collaboration Colleague Awarded $3M to Conduct First Diamond Mechanosynthesis Experiments
Professor Philip Moriarty of the Nanoscience Group the School of Physics at the University of Nottingham (U.K.) has been awarded a five-year $3M grant by the U.K. Engineering and Physical Sciences Research Council (EPSRC) to perform a series of laboratory experiments designed to investigate the possibility of diamond mechanosynthesis (DMS). DMS is a proposed method for building diamond nanostructures, atom-by-atom. Moriarty’s experiments begin in October 2008.
The Nottingham work grew out of continuing discussions on DMS between Moriarty and Robert Freitas, a Senior Research Fellow at the Institute for Molecular Manufacturing (IMM) (Palo Alto, California, U.S.).
Freitas and Ralph Merkle, also a Senior Fellow at IMM, founded the Nanofactory Collaboration in 2001 to pursue molecular manufacturing via DMS. Moriarty is interested in testing the viability of positionally-controlled atom-by-atom fabrication of diamondoid materials as described in the Freitas-Merkle minimal toolset theory paper. Moriarty’s efforts will be the first time specific predictions of DFT in the area of mechanosynthesis will be rigorously tested by experiment.
The article goes into more detail, but the implication for your longevity is this:
DMS is the first step on the way to full-blown nanomedicine. Nanomedicine may be the holy grail of indefinite lifespans. Next week, we’ll go a little deeper and take a peek into the future that nanomedicine has in store for you.
______________________________
LATEST HEALTHY LIFE EXTENSION HEADLINES

Calorie Restriction: Animals Versus People (September 25 2008) http://www.sciencedaily.com/releases/2008/09/080924151018.htm
The present scientific consensus on calorie restriction in humans is that it will do wonderful things for your health and resistance to age-related disease, but won't extend the maximum human life span to the same degree that is seen in lower animals: "In the majority of the animal models of longevity, extended lifespan involves pathways related to a growth factor called IGF-1 (insulin-like growth factor-1). In calorie-restricted animals, levels of circulating IGF-1 decline between 30 percent and 40 percent. We looked at IGF-1 in humans doing calorie restriction [and] found no difference in IGF-1 levels between people on calorie restriction and those who are not. We know there are two major influences on IGF-1 levels: calorie intake and protein intake. So we decided to look at the influence of protein. Six [human testers] agreed to lower their protein intake and after three weeks their circulating IGF-1 declined dramatically. It's much easier to restrict protein than to restrict calories. If our research is on the right track, maybe humans don't need to be so calorie restricted. Limiting protein intake to .7 or .8 grams per kilogram per day might be more effective. That's just a hypothesis. We have to confirm it in future studies."

Nitric Oxide and Aging Blood Vessels (September 24 2008) http://pmid.us/18805864
Nitric oxide is important in the operation of the endothelium - the lining of blood vessels - but diminishes with age: "The normal endothelium exerts a major vascular protecting role by secreting substances, above all nitric oxide (NO). In disease conditions (such as the presence of cardiovascular risk factors) the activation of endothelial cells can lead to the production and release of contracting factors, which counteract the beneficial effects of NO, and reactive oxygen species (ROS), which in turn cause NO breakdown. Aging has been demonstrated to be associated to a progressive impairment in endothelial function both in conduit arteries and resistance vessels, mainly because of an increased production of ROS.

Therefore, it is conceivable that endothelial dysfunction plays a major role in favoring age-related increased cardiovascular risk in the elderly. "This is an example of the way in which age-damaged cells cause problems in the normal operation of surrounding tissue: cells taken over by damaged mitochondria are exporting reactive oxygen species that breakdown NO, and senescent cells are pushing out their own cocktail of unhelpful chemical instructions as well.

Out of Context, Many Old Cells Work Just Fine (September 23 2008) http://pmid.us/18802086
It is a recurring theme in stem cell and immune system research that cells removed from the context of the aging cellular environment can do their jobs just as well as cells in a young environment: "Understanding how aging impacts the function of memory CD4 T cells is critical for designing effective vaccines. Our studies show that immunological memory generated during youth functions well into old age, whereas that generated later in life functions poorly. This is the result of declines in the function of naive CD4 T cells from aged individuals and contributes to reduced efficacy of vaccines in the elderly. To begin to identify the cause of this defect, we examined the function of memory T cells generated from bone marrow precursor cells (BMPC) from young or aged mice in young hosts. In two different models, memory cells derived from young and aged BMPC exhibit good ex vivo and in vivo function. Importantly, memory CD4 T cells generated from aged BMPC exhibit potent cognate helper function for humoral responses, which are critical for effective immunization. These results indicate that there are no apparent age-related intrinsic defects in BMPC with regards to generation of functional memory T cells." As for many aspects of aging, the problem is one of failing systems and signal controls, not failing components.

NOTE: Maybe many do work fine, but we believe most don’t, due to accumulated mutations.

A Recellurization Update (September 23 2008) http://www.popsci.com/node/24069
Via Popular Science: "Some people say they can grow a heart from scratch in 10 years, which is ridiculous. But Dr. Taylor's approach is more realistic because it's so simple and elegant. By using an existing heart, she's taken away all of the structural issues. Taylor's system involves flushing animal hearts of cells using a cleanser, at which point only the extracellular matrix remains and 'the hearts look almost clear'. The next step is to infuse the hearts with a mix of mature and progenitor cardiac cells, which can come from a patient's own body to ensure compatibility. Incredibly, for reasons the team still doesn't understand, the cells seem to know how to divide and proliferate into cardiac tissue inside the empty-shell hearts. This year, Taylor has continued to forge ahead toward her goal of creating transplantable, made-to-order human organs. Soon after she published her rat-heart results, she started working on making recellularized pig hearts - closer in size and shape to the human equivalent - that could pump blood and generate electrical impulses. Our hope is that someday we'll be able to take a cadaver or pig organ, decellularize it, and transplant your own cells into the matrix to make an organ that matches your body."

A Potential Downside to Exercise Mimetics (September 22 2008) http://ouroboros.wordpress.com/2008/09/22/amp-activated-kinase-the-target-of-exercise-mimetics-may-contribute-to-photoaging-and-cell-death/
From Ouroboros: "AMP-activated kinase (AMPK) agonists mimic the effects of exercise, raising the possibility of a 'workout pill' that could simulate the effects of vigorous activity. The applications to human health are, to mildly understate the case, significant; it sounds almost too good to be true, and it leaves one looking for the catch. It turns out that AMPK is activated by certain types of genotoxic stress, and contributes to UV-induced apoptosis in the skin. Activation of AMPK could exacerbate the pro-aging effects that UV light exerts on the skin. Judging from the peroxide results, this also applies to endogenously generated reactive oxygen species (ROS) - which one can't avoid by simply staying out of the sun. Before we panic and throw the exercise mimetic baby out with its carcinogenic bathwater, I'd want to see whether AMPK agonists like AICAR do in fact synergize with stresses like UV and peroxide to increase apoptotic cell death in the skin. If they do, well, I think we found that catch."

More Multipotent Stem Cells Discovered (September 22 2008) http://www.eurekalert.org/pub_releases/2008-09/chop-pri092208.phpFrom EurekAlert!: "The scientists [identified] cells known as pericytes that are multipotent, meaning they have broad developmental potential. Pericytes are found on the walls of small blood vessels such as capillaries and microvessels throughout the body and have the potential to be extracted and grown into many types of tissues. We believe pericytes represent one of the most promising sources of multipotent stem cells that scientists have been searching for in the quest to make regenerative medicine possible. These cells can be extracted easily and painlessly from convenient sources such as fat tissue, dental pulp, umbilical cord and placental tissue, then grown in culture to large numbers and, possibly, re-injected into the patient to heal a broken bone, a failing joint or an injured muscle. Researchers were able to identify pericytes in all human tissues they analyzed, including muscle, fat, pancreas, placenta and many other samples. Through purification in the lab, these pericytes could then be coaxed into becoming whatever type of tissue the scientists desired. For instance, the researchers took pericytes from the pancreas and then reinjected them into an injured muscle. The cells immediately began regenerating muscle tissue."

Las Vegas Longevity Workshop

Last week, I mentioned the longevity workshop I attended in Las Vegas. This week, I’m going to illustrate how hanging out with the participants energized me, and I’m going to talk a little about the workshop itself.

First, let me tell you why it was such a positive event for me.

We had 16 attendees, plus me. Every one of them, all 16, shared a positive upbeat outlook on life.

Can you think of someone who brightens up your day by just walking into the room? Don’t you have someone in your life who you just love hanging around, someone who lifts your spirits by their mere presence? How about someone who shares your values, aspirations and plans?

OK, now roll those people into one… then multiply that person by 16. That’s who I spent the weekend with… 16 energizers.

In fact, it gets better. Half the attendees were geniuses and leaders in their respective fields. I’m totally in awe of some of them. They’re so brilliant, they totally humble me.

Now if that’s not enough, the workshop topic was something I am passionate about – life insurance!

What? Life insurance? I know, I know, you’re probably thinking I’ve gone off the deep end, or I’m some sort of closet life insurance salesman. Nothing could be further from the truth. I did in fact sell life insurance in a previous life, but that was traditional life insurance… and I hated it.

No, this workshop was about the only “pure” form of life insurance. Not the kind you can only benefit from by dying (which is actually “death insurance”), but the kind that could keep you from dying in the first place… Cryonics! More specifically, our topic was the strategy to preserve your assets if you experience clinical death, get cryonically preserved and get resuscitated. In other words, maybe you can “take it with you” after all.

If you’re not familiar with cryonics, research has shown that dying is a gradual process which starts after, not when, our hearts or brain waves stop. Our cells die gradually, over time. Cryonics is the science that halts this dying process with low-temperature technologies, stemming from the field of cryobiology.

If the cryonics rescue team reaches patients in time after legal death, they may be able to place them into suspended animation until such time as cures for what “killed” them are developed, and when age-reversal technologies are mature. At that time, they plan on fixing you and waking you up.

A long-shot? Maybe. Whacky? If you think so, consider this:

Cryonics depends largely on two technologies. One is cryobiology, a well-proven field that deals with ultra-low temperatures. In this case, that means storing human tissue at liquid nitrogen temperatures for future therapies. This has been routinely done for many years.

The other is neurobiology, again, a totally legitimate and non-controversial field.

So it follows that it is just as legitimate to store and recover the brain (where your memory resides) as it is to store and recover any other tissue. So cryonics should work.

Then we add another emerging, and soon to be maturing tool… regenerative medicine. We’re already growing replacement organs, and soon, they promise to be as good, or even better than the originals. You have read a lot about this in previous issues of this newsletter. Again, a well-accepted field.

As these technologies are fine-tuned, they may be more than enough for resuscitating patients. But there’s more.

Another technology that may be enormously helpful for even more perfect rescue from suspension is nanotechnology. There’s already more work in this field than I can ever hope to keep up with. Full-blown nanomedicine may be developed in as little as 19 years.

So you might look at cryonics as the purest form of life insurance. Insurance is something you hope you never need but are glad you have when you do need it… when it is no longer for sale.
________________________________________________

LATEST HEALTHY LIFE EXTENSION HEADLINES

Progress in Bypassing Mitochondrial Damage (September 05 2008) http://www.eurekalert.org/pub_releases/2008-09/cp-gtp082808.php
Allotopic expression of genes normally found in mitochondrial DNA is a core portion of the Strategies for Engineered Negligible Senescence. It is the process of inserting a copy of vital mitochondrial genes into the cell nucleus, and then figuring out how to get the proteins produced by those genes back to the mitochondria where they are needed. This could eliminate the contribution of mitochondrial DNA damage to aging. A technique for doing all this is now demonstrated in rats: "We obtained a complete and long-term restoration of mitochondrial function in human fibroblasts in which the mitochondrial genes ATP6, ND1, and ND4 were mutated. ND1 and ND4 are mutated in nearly all cases of Leber hereditary optic neuropathy (LHON). LHON is the most common mitochondrial disorder and is characterized by a loss of vision. They introduced the human ND4 gene with the mutation present in the majority of LHON patients into rat eyes. The treatment caused retinal ganglion cells (RGCs) to degenerate significantly when compared to those from control eyes and was associated with decreased visual performance. Importantly, reintroducing normal ND4 led to prevention of RGC loss and visual impairment, effectively rescuing the animals from impending blindness. These data represent the 'proof of principle' that optimized allotropic expression is effective in vivo and can be envisaged as a therapeutic approach for mtDNA-related diseases."

Reactive Carbonyl Species, ALEs, and Aging (September 04 2008) http://pmid.us/18721793
Free radicals (such as reactive oxygen species) are increasingly generated with age - this is the end of a long chain of consequences that starts with damaged mitochondrial DNA. How do those oxidizing agents actually cause widespread harm to bodily systems? This paper gives an overview of one broad set of mechanisms, wherein step one is the creation of reactive carbonyl species (RCS) by free radicals: "Most of the biological effects of RCS [are] due to their capacity to react with cellular constituents, forming advanced lipoxidation end-products (ALEs). Compared to reactive oxygen and nitrogen species, lipid-derived RCS are stable and can diffuse within or even escape from the cell and attack targets far from the site of formation. Therefore, these soluble reactive intermediates, precursors of ALEs, are not only cytotoxic per se, but they also behave as mediators and propagators of oxidative stress and cellular and tissue damage. The causal role of ALEs in aging and longevity is inferred from the findings that follow: a) its accumulation with aging in several tissues and species; b) physiological interventions (dietary restriction) that increase longevity, decrease ALEs content; c) the longer the longevity of a species, the lower is the lipoxidation-derived molecular damage; and finally d) exacerbated levels of ALEs are associated with pathological states."

Update on the Longevity Science Amex Members Project (September 04 2008) http://blog.methuselahfoundation.org/2008/09/an_update_on_your_votes_and_un.html
From the Methuselah Foundation blog: "I'm pleased to say that the pro-longevity science community rallied to vote the Amex Members Project submission "Undergrads Fighting Age Related Disease" into the top 25 projects by vote totals - and made it the most discussed project of all. Thank you! That discussion is still ongoing, by the way, and people unfamiliar with longevity research have questions about the project. Feel free to jump in and help answer them. What comes next? Well, between now and September 9th - less than a week away - the Members Project advisory panel will look at the projects, votes, and discussions, and announce the final 25. Those 25 projects will be voted on by Amex card holders to determine which 5 will be funded. So, all you generous folk who rounded up your friends and spread the word: we're going to do it all again for those with American Express cards starting on the 9th. We here at the Methuselah Foundation are looking forward to it!"

Another Regenerative Strategy for Hearing Loss (September 03 2008) http://www.eurekalert.org/pub_releases/2008-09/ctco-hrm090308.php
Following on from the gene therapy approach for age-related deafness mentioned a few days ago, here's a cell-based therapy via EurekAlert!: "hearing loss due to cochlear damage may be repaired by transplantation of human umbilical cord hematopoietic stem cells. The team used animal models in which permanent hearing loss had been induced by intense noise, chemical toxicity or both. Cochlear regeneration was only observed in animal groups that received HSC transplants. Researchers used sensitive tracing methods to determine if the transplanted cells were capable of migrating to the cochlea and evaluated whether the cells could contribute to regenerating neurons and sensory tissue in the cochlea. Our findings show dramatic repair of damage with surprisingly few human-derived cells having migrated to the cochlea. A fraction of circulating HSC fused with resident cells, generating hybrids, yet the administration of HSC appeared to be correlated with tissue regeneration and repair as the cochlea in non-transplanted mice remained seriously damaged."

Metformin as Calorie Restriction Mimetic (September 02 2008)
http://pmid.us/18728386
This paper is illustrative of the thinking that leads to trying anti-diabetic drugs as calorie restriction mimetics: "Studies in mammals have led to the suggestion that hyperglycemia and hyperinsulinemia are important factors both in aging and in the development of cancer. It is possible that the life-prolonging effects of calorie restriction are due to decreasing IGF-1 levels. A search of pharmacological modulators of
insulin/IGF-1 signaling pathway (which resemble effects of life span extending mutations or calorie restriction) could be a perspective direction in regulation of longevity. Antidiabetic biguanides are most promising among them. Here we show the chronic treatment of female outbred SHR mice with metformin (100 mg/kg in drinking water) slightly modified the food consumption but decreased the body weight after the age of 20 months, slowed down the age-related switch-off of estrous function, increased mean life span by 37.8%, mean life span of last 10% survivors by 20.8%, and maximum life span by 2.8 months (+10.3%) in comparison with control mice." Full calorie restriction does better than that (30-40% maximum life span extension), but this is a strong argument for its effects on insulin metabolism to be one cause of enhanced health and longevity.

Another Human Longevity Gene Association (September 02 2008) http://www.telegraph.co.uk/earth/main.jhtml?view=DETAILS&grid=&xml=/earth/2008/09/01/sciage101.xml
The Telegraph reports on confirmation that a class of longevity genes indentified in lower animals also has an effect on human populations: "The gene linked with better health and a longer life is called FOXO3A and although similar genes have been shown to prolong life span in other species, this is the first time that FOXO has been linked directly to longevity in humans. Each gene comes in two copies and the team found the longevity effect of this letter was additive: those with one copy doubled their odds of living an average 98 years. Men who had two G copies did even better and almost tripled their odds of living nearly a century, and were markedly healthier at older ages. We screened 213 of the long-lived participants' DNA and 402 of the average-lived, focusing on five genes. These genes were selected for good reason because they involved in the insulin pathway and signaling, which studies of other animals have shown is linked with longevity." This doesn't tell us laypeople more than we already knew: that insulin metabolism is significant in health and longevity variations within a species.

On the Way to Controlling Telomerase (September 01 2008) http://www.eurekalert.org/pub_releases/2008-08/twi-lso082608.php
Researchers are making progress in figuring how to control telomerase, and through it influence telomeres, cancer, and aging. From EurekAlert!: Researchers "have deciphered the structure of the active region of telomerase, an enzyme that plays a major role in the development of nearly all human cancers. The landmark achievement opens the door to the creation of new, broadly effective cancer drugs, as well as anti-aging therapies. Researchers have attempted for more than a decade to find drugs that shut down telomerase - widely considered the No. 1 target for the development of new cancer treatments - but have been hampered in large part by a lack of knowledge of the enzyme's structure. The findings [should] help researchers in their efforts to design effective telomerase inhibitors. Telomerase is an ideal target for chemotherapy because it is active in almost all human tumors, but inactive in most normal cells. That means a drug that deactivates telomerase would likely work against all cancers, with few side effects." Long-term deactivation will cause massive issues, of course, but that's not the intent for the moment. Given new information about telomerase and mitochondria in aging, there are potentially more interesting end results than good cancer therapies.

Two Groups of Friends

I divide my close friends into two general groups.

1. The Miscellaneous Group: This includes lifelong friends as well as recent acquaintances. I share either/or history and some values with this group. I see some frequently but most infrequently. All-in-all, group is shrinking in size. That’s because many of us have grown or are growing apart. In other words, we don’t have much in common anymore. And outside of rehashing old times (which I find more-and-more boring), hanging out together is pretty much a waste of time. The few that I do enjoy spending with share common goals and typically look forward rather than backwards.

2. Life Extensionists/Futurists: This is my favorite and larger group of the two. It’s also expanding rapidly. It’s rare to hear these members talking of the past, and they are far more stimulating. They typically live actively in the present with long-term positive views of the future. And for the most part, they do their best to insure a profound future for all of us. They may take various paths and contribute in a number of ways such as doing research, volunteering for various future-focused movements, building positive value-laced enterprises, running companies and foundations, marketing positive products and services and actively participating in events, seminars and workshops that point toward noble goals such as (my favorite) radical life extension.

All too often, I get bogged down in the sea of minutia and the distractions of business and life that tends to bury us if we’re not constantly on guard. One of the challenges in my life is to evaporate that sea to a puddle. I’m gradually succeeding, but I’m not there yet. So when I have the chance to shut everything else out and spend time with Group #2, it breathes new life into me. I enjoyed that pleasure the past two weekends.

Two weeks ago, I and a couple of M.D.s got to address a group of life extensionists.

Pure rapture.

Just associating with like-minded people energizes me beyond description. It also validates and reinforces my resolve to conquer aging in our lifetimes.

This past Saturday, I took part in a life extension workshop in Las Vegas. The personal and business challenges that sometimes consume me did not enter my mind the entire weekend. How could they? Almost every minute was spent with some very close friends and with some not as close, but still enormously treasured acquaintances. Every single one of them shares most of my deepest goals and aspirations.

Most people take a two week or longer vacation to recharge. For me, it only takes a day in the company of members of Group #2. If you consider yourself a member of this group, you’re invited to a get-together at my home in Huntington Beach, CA, tentatively scheduled for Sat, Nov 22nd. If so, email me for directions and a final date and time.

Next week I’ll tell you a little about last weekend’s workshop.
________________________________________
LATEST HEALTHY LIFE EXTENSION HEADLINES

Thinking About Replacing the Brain (August 29 2008) http://www.memebox.com/futureblogger/show/827-our-future-brain-damage-resistant-with-unique-new-abilities
Some thoughts on the decades following the biotechnology revolution from FutureBlogger: Once nanotechnology is as far advanced as biotechnology is today, what sorts of capabilities start to look plausible? "By the mid-2030s, we could be replacing brain cells with damage-resistant nanomaterials that process thoughts much faster than today's biological brains. The new brain would include our same consciousness, memories and personality that existed before the conversion, but it would run much faster and would increase our memory a thousand-fold. A daily pill would supply nanomaterials and instructions for nanobots to format new neurons and position them next to existing biological brain cells to be replaced. These changes would be unnoticeable to us, but within six months, we would be enjoying our new brain. Should a person with the new damage-resistant brain die in an accident, their body could be a total loss, but the brain would survive. Biological brains die within minutes after the heart stops; our new brain will simply turn itself off and wait for a new power supply. All memories and consciousness would remain intact after a fatal accident. Rescue workers would remove the brain from the deceased body and reinstall it into a newly-cloned body." A lot of work remains to be accomplished before the golden future becomes a reality - first things first.

Vote For Amex Funding For Longevity Science (August 28 2008) http://www.membersproject.com/project/view/BVVE2C
The Methuselah Foundation volunteers are looking for more signatures in the next five days to help put the "Undergrads Fighting Age Related Disease" project high in the top 25 Amex Members Projects - and thus eligible for some of the $2.5 million in funding offered by American Express. There are five days left to put your name to this project in support: 1200 signatures have been gathered in the past two weeks, putting longevity science solidly in the running. At least that many more votes are needed before voting closes - which is where you and your friends come in. Visit the Methuselah Foundation blog or the project Facebook group to find out how to sign up - or just click through to this project and follow the directions. You don't have to be an American Express member, but you do have to be a US resident. One last thing: it's important to note that of all the projects submitted to date, Undergrads Fighting Age Related Disease has by far the most comments. This counts heavily in the final selection, so jump into the project comments section and tell the world why you support longevity science and the defeat of age-related disease.

Another Advance In Reprogramming Cells (August 28 2008) http://www.sciencedaily.com/releases/2008/08/080828082819.htm
As ScienceDaily notes, researchers "report having achieved what has long been a dream and ultimate goal of developmental biologists - directly turning one type of fully formed adult cell into another type of adult cell. The team is able to turn mouse exocrine cells, which make up about 95 percent of the pancreas, into precious and rare insulin-producing beta cells. Unlike the process involved in creating induced pluripotent stem cells (iPS) [this] direct reprogramming technique does not require turning adult cells into stem cells and then figuring out how to induce them to differentiate into a desired cell type. We're intrigued by the possibility that this approach, which has worked for pancreatic insulin-producing cells, could be more widely applied to many kind of cells, especially those that are lost in disease or following injury. And at the same time, we are exploring the possibility of using this general approach in a clinical context to make new beta cells for patients."

An Interview With Doug Melton (August 27 2008) http://www.technologyreview.com/printer_friendly_article.aspx?id=21307
The Technology Review interviews researcher Doug Melton: "If a patient has Parkinson's disease, their dopamine-producing cells are gone. We don't understand anything about what makes those cells go away - the field is kind of stuck because you can't watch the progression of the disease. Stem cells can make neurons in a dish. Imagine you have iPS cells from a healthy person and from a Parkinson's patient. If you make dopamine neurons from both sets of cells in separate dishes, you can look at what went wrong with the diseased stem cell. The same approach will work with different degenerative diseases, such as diabetes or ALS. I think it will change the way degenerative diseases are studied - we'll reduce the whole process of disease to a petri dish. Within a few years, researchers the world over should have access to disease-specific cells that can be turned into cell types defective in a particular disease. Science clearly works best when you have a lot of bright, motivated people working on these problems. The institute has sent thousands of human embryonic stem-cell lines to hundreds of labs all over the world. We like to think that has been helpful in encouraging basic research on embryonic stem cells."

Microglia Versus Alzheimer's (August 26 2008) http://www.sciencedaily.com/releases/2008/08/080825194705.htm
Researchers are attempting to convince the body's defenses to attack the amyloid plaques of Alzheimer's disease (AD): "by stimulating a brain cell called a microglia the cells will partially engulf the senile plaques ... [this is] the first time that this phenomenon, believed to take place in living brain, has been duplicated in the laboratory. The plaques themselves are not sufficient microglial activators. But when the microglia were treated with inflammatory stimulants, they attacked the plaques. In AD patients, microglia are not coping with the plaque build-up. Therefore plaques accumulate faster than the microglia can digest them. If we can enhance microglial digestion of these plaques, we will have a fighting chance to eliminate AD. The next step is to find a therapeutic drug that will stimulate the microglia to devour the plaques." Time will tell whether new methods of

The Bad Trends (August 25 2008) http://www.futurepundit.com/archives/005479.html
There are plenty of good trends in medicine research and development. The trend in bioinformatics and computational power, for example. Unfortunately, some of the bad trends are blocking movement of research into the clinic. Via FuturePundit: "Why do terminally ill patients have to wait so long to get access to the only treatments that hold any promise of saving their lives? And why is it not their right to decide? The FDA approved just 16 new drugs last year, and is on pace to approve only 18 this year. That's down from a high of 53 in 1996 and 39 in 1997. This trend does not bode well for the development of rejuvenation therapies. The FDA will hold off approval of an anti-cancer drug for people who have a fatal disease. Never mind that people who have a fatal disease are going to die anyway. The FDA won't let people take a risk when they have little to lose. That makes no sense to me. Rejuvenation therapies are going to treat that fatal disease called aging. Absent those therapies we are all going to die from complications of aging. Faced with rising risks of death combined with increasing pain and disablement people should be given wider latitude to try new and unproven therapies." The FDA should turn down completely; it is a roadblock to progress, and the cause of great and ongoing suffering.
______________________________
DISCLAIMER: News summaries are reported by third parties, and there is no guarantee of accuracy. This newsletter is not meant to substitute for your personal due diligence and is not to be taken as medical advice. For originating report, please see www.longevitymeme.org/newsletter/.

Funding Extreme Life Extension Research

For you serious readers, some say Dr. Leonid Gavrilov’s book, Biology of Life Span: A Quantitative Approach, has the potential to change the future of this country for the better, if its ideas reach members of Congress and other representatives of the U.S. government. Get more information at http://tinyurl.com/5x5ror

Now we’re going to wrap up our previous discussion about how we’re going to fund extreme life extension research.

How about all the private money? Where is it all going? Unfortunately, many popular investments may be ruining your health and shortening your life instead of extending it. And you may be unknowingly contributing to it. If you are invested in mutual funds, retirement funds, hedge funds, the chances are, you are invested in what I sometimes call “pro-death industries”. They include fast foods, processed foods, alcoholic and soft drinks and tobacco.

These industries make money… lots of it. That’s why savvy money managers invest in them. But they kill in two insidious ways. First, the products can shorten your life. Second, they divert sorely needed funds needed to develop life extending products, technologies and services.

Doesn’t it make sense to commit a portion of your wealth to technologies that cure diseases, promote wellness and extend healthy life?

Sure, we can wait until large funding sources finally catch up. Meanwhile though, over 100,000 lives get snuffed out every single day from aging. A five year delay equates to 185 MILLION more lost lives. Scientists tell us they can start making an impact with only a few million more dollars per year, so we simply can’t wait for nature to run its course. A delay could cost you or a loved one your life.

So I urge you to do three things:

1. Incorporate the 7 simple steps outlined in Life Extension Express into your life and gain 5-20 years... or more from the health steps you practice now. You will create a brighter tomorrow for yourself when you take some simple steps today.


2. Invest in some of these technologies or donate to Maximum Life Foundation, Methuselah Foundation, InnerSpace Foundation or Immortality Institute to support them.


3. Keep abreast of advances and breakthroughs that could push you over the longevity finish line.

As I see it, extreme life extension in our lifetimes will ultimately depend on several factors: (a) how much funding we can raise; (b) how soon we can raise the money; (c) how well you take care of yourself in the interim and (d) your ability to dodge accidents, warfare, terrorism, natural disasters or epidemics. Don’t wait until it’s too late – and then wish you would have spent a little time, money and effort for prevention.

______________________________

LATEST HEALTHY LIFE EXTENSION HEADLINES

More Compelling Reasons to Exercise (August 22 2008) http://pmid.us/18716044

Here is another study to add to the huge stack of research telling us that exercise is good for healthy longevity: "We determined whether reduced insulin sensitivity, mitochondrial dysfunction and other age-related dysfunctions are inevitable consequences of aging or secondary to physical inactivity. Insulin-induced glucose disposal and suppression of endogenous glucose production were higher in the trained young and older people but no age-effect was noted. Age-related decline in mitochondrial oxidative capacity was absent in endurance-trained individuals. Although endurance trained individuals exhibited higher expression of mitochondrial proteins, mtDNA, and mitochondrial transcription factors there were persisting effects of age. SIRT3 expression was lower with age in sedentary but equally elevated in endurance trained individuals. ... The results demonstrate that reduced insulin sensitivity is likely related to changes in [level of body fat] and physical inactivity rather than an inevitable consequence of aging. The results also show that regular endurance exercise partly normalizes age-related mitochondrial dysfunction, although there are persisting effects of age at the level of mtDNA abundance, nuclear transcription factors, and mitochondrial protein expression. Furthermore, exercise may promote longevity through pathways common to effects of caloric restriction."

Ouroboros on Biomarkers and Telomere Length (August 22 2008) http://ouroboros.wordpress.com/2008/08/21/telomere-dysfunction-markers-as-biomarkers-of-aging/

From Ouroboros: "How old are you? At present, the best experimental approach to that question is to inspect your driver's license; we are very good at measuring chronological age, but far worse at measuring physiological age. Until we have such a tool, questions like 'how rapidly is this individual aging?' and 'is this treatment having a positive effect on the rate of aging?' will be meaningless. So, the race is on to find useful biomarkers of aging. Telomere length is a tantalizing biomarker for the aging process: it's positively correlated with life expectancy and negatively correlated with stress and disease. If telomere shortening is a biomarker of aging, then the measurable consequences of telomere shortening should also function as biomarkers, i.e., aging bodies should contain high levels of factors secreted by cells with dysfunctional or critically short telomeres. According to a recent paper by Jiang et al., this is indeed the case. The proteins identified here accumulate with age - [and] they accumulate faster in subjects who are both aged and suffering from age-related disease; in other words, in people whom we might intuitively assign to the 'more rapidly aging' category."

Weight Gain Cast as a Result of Neural Damage (August 21 2008) http://www.eurekalert.org/pub_releases/2008-08/mu-kc082108.php

Hopefully you don't need more reasons to eat a sensible diet by now, but here's another. EurekAlert! passes on a theory to account for what happens to those of us who load up the carbohydrates over the years: "key appetite control cells in the human brain degenerate over time, causing increased hunger and potentially weight-gain as we grow older. Appetite-suppressing cells are attacked by free radicals after eating and [the] degeneration is more significant following meals rich in carbohydrates and sugars. People in the age group of 25 to 50 are most at risk. The neurons that tell people in the crucial age range not to over-eat are being killed-off. When the stomach is empty, it triggers the ghrelin hormone that notifies the brain that we are hungry. When we are full, a set of neurons known as POMCs kick in.. However, free radicals created naturally in the body attack the POMC neurons. This process causes the neurons to degenerate over time, affecting our judgement as to when our hunger is satisfied .The free radicals also try to attack the hunger neurons, but these are protected by the uncoupling protein 2 (UCP2)." So eat more over the years and suffer neural damage that makes it harder not to eat more. We all have free will, but why make it harder for yourself?

Menstrual Blood as Source of Adult Stem Cells (August 20 2008) http://www.sciencedaily.com/releases/2008/08/080818220609.htm

Like heart damage, peripheral artery disease is open to comparatively simple stem cell therapies based on cell transplants. All that is needed is a low-cost source of suitable stem cells. From ScienceDaily: "Cells obtained from menstrual blood, termed 'endometrial regenerative cells' (ERCs) are capable of restoring blood flow in an animal model of advanced peripheral artery disease. A new study demonstrates that when circulation-blocked mice were treated with ERC injections, circulation and functionality were restored. [Researchers have] already performed clinical trials with adult stem cells for patients with peripheral artery disease. The advantage of ERCs is that they can be used in an 'off the shelf' manner, meaning they can be delivered to the point of care, do not require matching, and are easily injectable without the need for complex equipment." The ease with which a therapy can be implemented makes a great deal of difference to the speed with which it moves from laboratory to clinic.

Building Blood from Stem Cells (August 20 2008) http://www.timesonline.co.uk/tol/life_and_style/health/article4567387.ece

The Times has more on growing blood from stem cells: "Vials of human blood have been grown from embryonic stem cells for the first time during research that promises to provide an almost limitless supply suitable for transfusion into any patient. The achievement by scientists in the United States could lead to trials of the blood within two years, and ultimately to an alternative to donations that would transform medicine. If such blood was made from stem cells of the O negative blood type, which is compatible with every blood group but is often in short supply, it could be given safely to anybody who needs a transfusion. One of the biggest safety hurdles that must be cleared before stem-cell therapies enter clinical trials is the risk of uncontrolled cell growth causing cancer. Red blood cells, however, do not have nuclei that carry the genetic material that goes wrong in cancer, and thus should not present this danger. While a few red blood cells have been created from embryonic stem cells before, the ACT team is the first to mass-produce them on the scale required for medical use. They also showed that the red cells were capable of carrying oxygen, and that they responded to biological cues in similar fashion to the real thing."

A Profile of Robert Lanza (August 19 2008) http://discovermagazine.com/2008/sep/19-fighting-for-the-right-to-clone/article_print

Discover Magazine looks at one of the noteworthies of the stem cell research community: "The value of therapeutic cloning has long been clear to Lanza, who did his early work with South African heart transplant pioneer Christiaan Barnard. Starting from those early days, Lanza understood that the barrier to tissue transfer was rejection by the recipient. From an entire organ to a dose of embryonic stem cells, if the tissue's DNA came from anyone else, the transplant would be rejected without the aid of harsh immunosuppressive drugs. 'The treatment could be worse than the problem,' Lanza found. But embryonic clones, the source of an endless supply of stem cells imprinted with one's personal DNA, could alter the equation in favor of the patient and augur a paradigm shift in medicine on par with the changes brought about by antibiotics and vaccines. With the ability to become all of the blood cells - including your immune cells, red blood cells, all of your blood system, as well as vasculature, [hemangioblasts] have been biology's holy grail. What we discovered is that we can create literally millions or billions of these from human embryonic stem cells. We can use transient, intermediate cells like hemangioblasts as a toolbox to fix the adult so you don't have to have limbs amputated, so you may not have to go blind, to prevent heart attacks."

More DNA Damage Research, In Mice This Time (August 18 2008) http://pmid.us/18565572

What does nuclear DNA damage have to do with aging? The correlation is clearly there - older animals have more random nuclear DNA damage - but the mechanism by which increased damage might lead to some portion of degenerative aging is up for debate. A recent paper shows that the correlation extends to calorie restriction and some genetic manipulations that extend life: "Genetic instability has been implicated as a causal factor in cancer and aging. Caloric restriction (CR) and suppression of the somatotroph axis significantly increase life span in the mouse and reduce multiple symptoms of aging, including cancer. To test if in vivo spontaneous mutation frequency is reduced by such mechanisms, we crossed long-lived Ames dwarf mice with a C57BL/6J line [to] measure mutant frequencies. Four cohorts were studied: (1) ad lib wild-type; (2) CR wild-type; (3) ad lib dwarf; and (4) CR dwarf. Results indicate that two major pro-longevity interventions in the mouse are associated with a reduced mutation frequency. This could be responsible, at least in part, for the enhanced longevity associated with Ames dwarfism and CR."

"

Back to Top

Financial Support for Aging Research

posted on August 18, 2008

Last week, we talked about the potential (optimistic) cost to reverse aging within the next couple of decades.

Historically financial support for aging research and efforts to extend the healthy lifespan has been spotty. Venture capital firms typically aim for profitable exits from their investments within two to four years. The research and product development we support typically takes longer to mature. Governments aren’t providing much funding. Pharmaceutical and biotech companies’ support of basic aging research is hindered due to the fact that there are no generally accepted biomarkers for human aging that would allow the FDA to approve a drug designed to slow the aging process. These companies are forced to develop drugs for specific diseases. And the FDA doesn’t recognize aging as a disease.

For example, The New York Times looks at Sirtris Pharmaceuticals: "The hope is that activating sirtuins in people would, like a calorically restricted diet in mice, avert degenerative diseases of aging like diabetes, heart disease, cancer and Alzheimer's.”

Dr. Christoph Westphal, the chief executive of Sirtris, said of the potential of the resveratrol based drugs they are developing, “I think that if we are right, this could extend life span by 5 or 10 percent.” He added that his goal was to develop drugs against specific diseases, with the extension of life being “almost a side effect of our medicine.”

There is no FDA category for longevity drugs, so if the company is to submit a drug for approval, it needs to be for a specific disease. However, longevity is what has motivated the researchers and what makes the drugs potentially so appealing.

There you have the most serious problem facing longevity science today. The FDA does not allow its direct application. Until this changes, no serious investment will be made in the US to bring longevity science to the clinic. This is a tragedy of astronomical proportions and is beyond belief.

Congress did supplement scarce aging research dollars by establishing the National Institute on Aging in 1974, but that money has primarily gone to disease specific research, such as Alzheimer's disease, or towards the behavioral aspects of aging.

Next week, we’ll look at the possibilities of significant private money finally joining the hunt.

_________________________________________________________

VOTE FOR "UNDERGRADS AGAINST AGE RELATED DISEASE"

I don't know if you're familiar with the American Express Members Project: It is an open vote to determine how that company will set up a philanthropic program. One of the suggested projects was put forward by a Methuselah Foundation volunteer, and we're looking for enough votes to move it into the next round of consideration:

"You can help by voting: it's free and won't take more than a few minutes. We just need you to go to the Members Projects website and nominate the "Undergrads Against Age Related Disease" project. You don't need to be an Amex card holder, but you do need to be a US resident."

You'll find the project description at the following link:

http://www.membersproject.com/project/view/BVVE2C

"A program that utilizes college undergraduates to perform research in a variety of scientific venues surrounding fighting age related diseases such as Alzheimer's, Parkinson's, Heart Disease, [Cancer, and] overall extension of healthy human life. Hiring researchers is exceedingly expensive. By outsourcing projects to undergraduate students, laboratory use and labor costs are negligible, and the students receive college credit for their work"

______________________________

LATEST HEALTHY LIFE EXTENSION HEADLINES

Towards Tissue Engineered Corneas (August 15 2008) http://www.hindustantimes.com/storypage/storypage.aspx?id=34901c8e-1148-44b8-ae83-395922ea0f64

From the Hindustan Times: "Half a dozen eye hospitals in India are collaborating with a research centre in Chennai to create the inner layer of the cornea, the vital window of the human eye. Nichi-In Centre for Regenerative Medicine (NCRM) hopes to make corneal endothelium (inside cell layer) available on a commercial scale. About 100,000 people are in need of eye transplant every year, yet only about 10,000 are able to get donated eyes. The wait for a donor can be endless for the other 90,000. Imagine what a boon it will be if an eye stem cell bank could provide these lab generated endothelial layer of the cornea. The eye has three main parts. The first is the cornea, which is a transparent film like structure that transmits light into the eye. The other two are the lens and retina. During eye transplant, only the cornea is taken from the donor, not the whole eye. Nichi-In is now growing the animal and human corneal inner layer cells on a nano-scaffolding. The research centre is hoping to begin phase I clinical trials on humans in six months."

Ouroboros on Open Science (August 15 2008) http://ouroboros.wordpress.com/2008/08/14/opening-science-how-unconferences-changed-my-life/

Open science, analogous to open source software development, is the way of the future. It greatly increases diversity and speed of work by lowering the cost of information, and thereby allowing many more people to participate in research. In a world in which information transmission is easy, it makes no sense to lock up scientific data. Publish early, publish often should be the mantra. From Ouroboros: "The world implied by these concepts is one of radical sharing, in which credit still goes where credit is due but by dramatically different mechanisms. Open science isn’t so much 'pay it forward' (though there is a bit of that) as an effort to create a (scientific) world in which no one is paying at all, a world in which there's no incentive to withhold or protect ownership of data. The science fiction writer Iain M. Banks once wrote that 'money implies poverty' - indeed, many of the current models of data ownership and publication, and their accompanying 'currencies' of proprietorship, prestige and closed-access publication, imply a world in which data is scarce and must be hoarded. But data is not scarce anymore."

Cryonics Versus Rejuvenation Medicine (August 14 2008) http://www.depressedmetabolism.com/2008/08/13/thomas-donaldson-on-cryonics-and-anti-aging/

Via Depressed Metabolism, arguments for a present focus on the development of cryonics over the development of rejuvenation medicine: "In his article 'Why Cryonics Will Probably Help You More Than Antiaging' (2004), cryonics activist Thomas Donaldson contrasts cryonics with antiaging as a means to life extension and argues that a major advantage of cryonics is that cryobiology research can move at a much faster pace than anti-aging research, especially as it pertains to humans. Not only that, but its progress almost totally lacks the problems of proving that an advance has happened. The state of a brain, or even a section of brain, after vitrification and rewarming to normal temperature, shows directly whether or not the method used improved on previous methods. Cryonic suspension is able at least to preserve our brains in a reversible form, allowing restoration of vital functions and looks likely to come much sooner [than rejuvenation medicine]." Which is all true - but problems left to other people to solve have a way of remaining unsolved. We should work on both cryonics and rejuvenation medicine, not leave the latter for future generations.

Removing the Worst Aspect of Chronic Infection (August 13 2008) http://www.eurekalert.org/pub_releases/2008-08/eu-twb_1080808.php

An important aspect of immune system aging is the lack of naive T cells resulting from long periods of chronic infection by viruses like cytomegalovirus. What if we could reconfigure the immune system to behave more rationally when presented with recurring threats, and thus not exhaust its resources? That might be a possibility: "preventing white blood cells' circulation by trapping them in the lymph nodes can help mice get rid of a chronic viral infection. Laboratory mice can fight off infection by the Armstrong strain of lymphocytic choriomeningitis virus (LCMV), but are vulnerable to chronic infection by a variant called clone 13. Infecting mice with the Armstrong strain sequesters white blood cells in the lymph nodes, while clone 13 does so less stringently. Our hypothesis was that if we could artificially induce conditions like those produced by the Armstrong strain, it would help the immune system clear an infection by clone 13. An experimental drug called FTY720 [prevents] white blood cells from leaving lymph nodes. Even if mice have a stable chronic LCMV clone 13 infection, treatment with FTY720 can still improve their immune response against LCMV enough to have them rid it from their systems. FTY720 appears to prevent 'exhaustion' in the group of white blood cells called CD8+ T cells."

Hourglass II: A Carnival of Biogerontology (August 13 2008) http://ouroboros.wordpress.com/2008/08/12/hourglass-ii-a-carnival-of-biogerontology/

From Ouroboros: "Welcome to the second installation of Hourglass, a blog carnival devoted to the biology of aging. The entries are representatives of the excellent (and growing) community of bloggers who are writing about biogerontology, lifespan extension technologies, and aging in general. Anne C. shares a parable about taking care of her friend Nigel the Fish and what that led her to realize about longevity: specifically, that environment is critical, and that the combination of extrinsic factors that one might collectively term 'nurture' can make all the difference between a short unhappy life and a long fulfilled one. Old and damaged cells enter a permanent growth arrest known as senescence, which is both good (because they can’t initiate tumors) and bad (because persistent senescent cells behave in a ridiculously antisocial manner, secreting growth factors and proteases that both encourage nearby tumors to metastasize and degrade tissue function). At his new site Anti-Ageing Research, Dominick Burton discusses ways in which specifically targeted cancer therapies might be adapted to attack senescent cells instead."

Building Better Tendons (August 12 2008) http://technology.newscientist.com/article/dn14512-labgrown-tendons-gradually-fade-to-bone.html

Laboratory tissue engineering continues to improve in sophistication, as noted by the New Scientist: "only now have researchers managed to make different tissues blend into one another, as they do naturally in the body. Such gradients are necessary for some structures and organs to function properly. In the body, gradients like this strengthen the ends of tendons that attach to bones. Currently, lab-grown tendons put into the body often fail at the attachment end because they lack this property. The new technique should lead to more lifelike artificially-grown tendons, and better treatments for injuries like ruptured Achilles tendons.

The technique could also be applicable to other tissues, such as blood vessels. At the heart of the new technique is a gene that triggers the fibroblast cells that make up tendons to start forming bone. The team used viruses carrying that gene to transform a tendon made from normal fibroblasts into one with a gradient of bony properties. So far, the researchers have shown that tendons made this way are stable when implanted under the skin of rats. The next step is to graft a tendon to connect bone and muscle in a rat and see if it really does perform better."

Demonstrating the Value of Exercise (August 12 2008) http://www.medicalnewstoday.com/articles/117929.php

Via Medical News Today, another reminder of the value of exercise: "US scientists comparing middle aged and older regular runners with healthy equivalents for more than 20 years found that vigorous regular exercise was linked to longer life and less disability in old age. Fries and his team had 538 members of a nationwide running club and 423 healthy controls from northern California fill in questionnaires every year for as long as they could, from 1984 to 2005. The mean disability score was higher for the controls than the runners at all stages of the study and went up with age in both groups, but on average, for runners the onset of disability started later. Runners' initial disability was 16 years later than nonrunners. Runners had a significantly lower risk of having a disability score of 0.5. 19 years into the study, 15 per cent of the runners and 34 per cent of the controls had died, and after adjusting for possible confounders, runners showed a greater chance of living longer. The differences in disability and longevity between the runner group and the control group continued to diverge at the end of the study, as the participants approached their 80th birthday."

Full Paper on Visceral Fat and Longevity (August 11 2008) http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2504027

You may recall a solid demonstration that visceral fat tissue negatively affects longevity from earlier this year. The full paper is now open access and available at PubMed Central: "Visceral fat (VF) accretion occurs in obesity and with aging, and a reduction in VF is a common phenotypic change in calorie-restricted [CR] mammals. VF has been shown to be the single most important determinant of metabolic syndrome, and its removal in rats results in improved insulin action and delays the onset of diabetes. Given the hazards associated with abdominal obesity, it seems plausible that the beneficial effects of CR on longevity may be due at least in part to an attenuation of VF. Our data clearly demonstrate that in mammals, VF removal and CR are associated with an increase in mean and maximum lifespan. The mean and maximum lifespan of CR rats was greater than that seen in VF-removed animals, suggesting that the life-prolonging benefit of CR is mediated in part by pathways other than those modulated by an attenuation of VF. By comparing median lifespans, we estimate that the contribution of CR to longevity in this model was 47 weeks, whereas VF removal was 9.5 weeks, as compared to [ad libitum]-fed rats, suggesting that VF reduction offered approximately 20% of the effect of CR on longevity."

Financial Support for Aging Research

Financial Support for Aging Research

Last week, we talked about the potential (optimistic) cost to reverse aging within the next couple of decades.
Historically financial support for aging research and efforts to extend the healthy lifespan has been spotty. Venture capital firms typically aim for profitable exits from their investments within two to four years. The research and product development we support typically takes longer to mature. Governments aren’t providing much funding. Pharmaceutical and biotech companies’ support of basic aging research is hindered due to the fact that there are no generally accepted biomarkers for human aging that would allow the FDA to approve a drug designed to slow the aging process. These companies are forced to develop drugs for specific diseases. And the FDA doesn’t recognize aging as a disease.
For example, The New York Times looks at Sirtris Pharmaceuticals: "The hope is that activating sirtuins in people would, like a calorically restricted diet in mice, avert degenerative diseases of aging like diabetes, heart disease, cancer and Alzheimer's.”

Dr. Christoph Westphal, the chief executive of Sirtris, said of the potential of the resveratrol based drugs they are developing, “I think that if we are right, this could extend life span by 5 or 10 percent.” He added that his goal was to develop drugs against specific diseases, with the extension of life being “almost a side effect of our medicine.”

There is no FDA category for longevity drugs, so if the company is to submit a drug for approval, it needs to be for a specific disease. However, longevity is what has motivated the researchers and what makes the drugs potentially so appealing.

There you have the most serious problem facing longevity science today. The FDA does not allow its direct application. Until this changes, no serious investment will be made in the US to bring longevity science to the clinic. This is a tragedy of astronomical proportions and is beyond belief.
Congress did supplement scarce aging research dollars by establishing the National Institute on Aging in 1974, but that money has primarily gone to disease specific research, such as Alzheimer's disease, or towards the behavioral aspects of aging.
Next week, we’ll look at the possibilities of significant private money finally joining the hunt.
_________________________________________________________

VOTE FOR "UNDERGRADS AGAINST AGE RELATED DISEASE"

I don't know if you're familiar with the American Express Members Project: It is an open vote to determine how that company will set up a philanthropic program. One of the suggested projects was put forward by a Methuselah Foundation volunteer, and we're looking for enough votes to move it into the next round of consideration:

"You can help by voting: it's free and won't take more than a few minutes. We just need you to go to the Members Projects website and nominate the "Undergrads Against Age Related Disease" project. You don't need to be an Amex card holder, but you do need to be a US resident."

You'll find the project description at the following link:

http://www.membersproject.com/project/view/BVVE2C

"A program that utilizes college undergraduates to perform research in a variety of scientific venues surrounding fighting age related diseases such as Alzheimer's, Parkinson's, Heart Disease, [Cancer, and] overall extension of healthy human life. Hiring researchers is exceedingly expensive. By outsourcing projects to undergraduate students, laboratory use and labor costs are negligible, and the students receive college credit for their work"
______________________________

LATEST HEALTHY LIFE EXTENSION HEADLINES

Towards Tissue Engineered Corneas (August 15 2008) http://www.hindustantimes.com/storypage/storypage.aspx?id=34901c8e-1148-44b8-ae83-395922ea0f64
From the Hindustan Times: "Half a dozen eye hospitals in India are collaborating with a research centre in Chennai to create the inner layer of the cornea, the vital window of the human eye. Nichi-In Centre for Regenerative Medicine (NCRM) hopes to make corneal endothelium (inside cell layer) available on a commercial scale. About 100,000 people are in need of eye transplant every year, yet only about 10,000 are able to get donated eyes. The wait for a donor can be endless for the other 90,000. Imagine what a boon it will be if an eye stem cell bank could provide these lab generated endothelial layer of the cornea. The eye has three main parts. The first is the cornea, which is a transparent film like structure that transmits light into the eye. The other two are the lens and retina. During eye transplant, only the cornea is taken from the donor, not the whole eye. Nichi-In is now growing the animal and human corneal inner layer cells on a nano-scaffolding. The research centre is hoping to begin phase I clinical trials on humans in six months."

Ouroboros on Open Science (August 15 2008) http://ouroboros.wordpress.com/2008/08/14/opening-science-how-unconferences-changed-my-life/
Open science, analogous to open source software development, is the way of the future. It greatly increases diversity and speed of work by lowering the cost of information, and thereby allowing many more people to participate in research. In a world in which information transmission is easy, it makes no sense to lock up scientific data. Publish early, publish often should be the mantra. From Ouroboros: "The world implied by these concepts is one of radical sharing, in which credit still goes where credit is due but by dramatically different mechanisms. Open science isn’t so much 'pay it forward' (though there is a bit of that) as an effort to create a (scientific) world in which no one is paying at all, a world in which there's no incentive to withhold or protect ownership of data. The science fiction writer Iain M. Banks once wrote that 'money implies poverty' - indeed, many of the current models of data ownership and publication, and their accompanying 'currencies' of proprietorship, prestige and closed-access publication, imply a world in which data is scarce and must be hoarded. But data is not scarce anymore."

Cryonics Versus Rejuvenation Medicine (August 14 2008) http://www.depressedmetabolism.com/2008/08/13/thomas-donaldson-on-cryonics-and-anti-aging/
Via Depressed Metabolism, arguments for a present focus on the development of cryonics over the development of rejuvenation medicine: "In his article 'Why Cryonics Will Probably Help You More Than Antiaging' (2004), cryonics activist Thomas Donaldson contrasts cryonics with antiaging as a means to life extension and argues that a major advantage of cryonics is that cryobiology research can move at a much faster pace than anti-aging research, especially as it pertains to humans. Not only that, but its progress almost totally lacks the problems of proving that an advance has happened. The state of a brain, or even a section of brain, after vitrification and rewarming to normal temperature, shows directly whether or not the method used improved on previous methods. Cryonic suspension is able at least to preserve our brains in a reversible form, allowing restoration of vital functions and looks likely to come much sooner [than rejuvenation medicine]." Which is all true - but problems left to other people to solve have a way of remaining unsolved. We should work on both cryonics and rejuvenation medicine, not leave the latter for future generations.

Removing the Worst Aspect of Chronic Infection (August 13 2008) http://www.eurekalert.org/pub_releases/2008-08/eu-twb_1080808.php
An important aspect of immune system aging is the lack of naive T cells resulting from long periods of chronic infection by viruses like cytomegalovirus. What if we could reconfigure the immune system to behave more rationally when presented with recurring threats, and thus not exhaust its resources? That might be a possibility: "preventing white blood cells' circulation by trapping them in the lymph nodes can help mice get rid of a chronic viral infection. Laboratory mice can fight off infection by the Armstrong strain of lymphocytic choriomeningitis virus (LCMV), but are vulnerable to chronic infection by a variant called clone 13. Infecting mice with the Armstrong strain sequesters white blood cells in the lymph nodes, while clone 13 does so less stringently. Our hypothesis was that if we could artificially induce conditions like those produced by the Armstrong strain, it would help the immune system clear an infection by clone 13. An experimental drug called FTY720 [prevents] white blood cells from leaving lymph nodes. Even if mice have a stable chronic LCMV clone 13 infection, treatment with FTY720 can still improve their immune response against LCMV enough to have them rid it from their systems. FTY720 appears to prevent 'exhaustion' in the group of white blood cells called CD8+ T cells."

Hourglass II: A Carnival of Biogerontology (August 13 2008) http://ouroboros.wordpress.com/2008/08/12/hourglass-ii-a-carnival-of-biogerontology/
From Ouroboros: "Welcome to the second installation of Hourglass, a blog carnival devoted to the biology of aging. The entries are representatives of the excellent (and growing) community of bloggers who are writing about biogerontology, lifespan extension technologies, and aging in general. Anne C. shares a parable about taking care of her friend Nigel the Fish and what that led her to realize about longevity: specifically, that environment is critical, and that the combination of extrinsic factors that one might collectively term 'nurture' can make all the difference between a short unhappy life and a long fulfilled one. Old and damaged cells enter a permanent growth arrest known as senescence, which is both good (because they can’t initiate tumors) and bad (because persistent senescent cells behave in a ridiculously antisocial manner, secreting growth factors and proteases that both encourage nearby tumors to metastasize and degrade tissue function). At his new site Anti-Ageing Research, Dominick Burton discusses ways in which specifically targeted cancer therapies might be adapted to attack senescent cells instead."

Building Better Tendons (August 12 2008) http://technology.newscientist.com/article/dn14512-labgrown-tendons-gradually-fade-to-bone.html
Laboratory tissue engineering continues to improve in sophistication, as noted by the New Scientist: "only now have researchers managed to make different tissues blend into one another, as they do naturally in the body. Such gradients are necessary for some structures and organs to function properly. In the body, gradients like this strengthen the ends of tendons that attach to bones. Currently, lab-grown tendons put into the body often fail at the attachment end because they lack this property. The new technique should lead to more lifelike artificially-grown tendons, and better treatments for injuries like ruptured Achilles tendons.
The technique could also be applicable to other tissues, such as blood vessels. At the heart of the new technique is a gene that triggers the fibroblast cells that make up tendons to start forming bone. The team used viruses carrying that gene to transform a tendon made from normal fibroblasts into one with a gradient of bony properties. So far, the researchers have shown that tendons made this way are stable when implanted under the skin of rats. The next step is to graft a tendon to connect bone and muscle in a rat and see if it really does perform better."

Demonstrating the Value of Exercise (August 12 2008) http://www.medicalnewstoday.com/articles/117929.php
Via Medical News Today, another reminder of the value of exercise: "US scientists comparing middle aged and older regular runners with healthy equivalents for more than 20 years found that vigorous regular exercise was linked to longer life and less disability in old age. Fries and his team had 538 members of a nationwide running club and 423 healthy controls from northern California fill in questionnaires every year for as long as they could, from 1984 to 2005. The mean disability score was higher for the controls than the runners at all stages of the study and went up with age in both groups, but on average, for runners the onset of disability started later. Runners' initial disability was 16 years later than nonrunners. Runners had a significantly lower risk of having a disability score of 0.5. 19 years into the study, 15 per cent of the runners and 34 per cent of the controls had died, and after adjusting for possible confounders, runners showed a greater chance of living longer. The differences in disability and longevity between the runner group and the control group continued to diverge at the end of the study, as the participants approached their 80th birthday."

Full Paper on Visceral Fat and Longevity (August 11 2008) http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2504027
You may recall a solid demonstration that visceral fat tissue negatively affects longevity from earlier this year. The full paper is now open access and available at PubMed Central: "Visceral fat (VF) accretion occurs in obesity and with aging, and a reduction in VF is a common phenotypic change in calorie-restricted [CR] mammals. VF has been shown to be the single most important determinant of metabolic syndrome, and its removal in rats results in improved insulin action and delays the onset of diabetes. Given the hazards associated with abdominal obesity, it seems plausible that the beneficial effects of CR on longevity may be due at least in part to an attenuation of VF. Our data clearly demonstrate that in mammals, VF removal and CR are associated with an increase in mean and maximum lifespan. The mean and maximum lifespan of CR rats was greater than that seen in VF-removed animals, suggesting that the life-prolonging benefit of CR is mediated in part by pathways other than those modulated by an attenuation of VF. By comparing median lifespans, we estimate that the contribution of CR to longevity in this model was 47 weeks, whereas VF removal was 9.5 weeks, as compared to [ad libitum]-fed rats, suggesting that VF reduction offered approximately 20% of the effect of CR on longevity."

Your perfect cure is prevention

Dear Future Centenarian,

A very close friend of mine’s father seems to have lost his will to live. Here is an aging former soldier of fortune who once had a zest for life experienced by few. Now, he lost interest in eating, in seeing a doctor and seemingly everything else, including his will to live.

This bothers me for a couple of reasons. First, someone close to me may lose her dad. And on a larger scale, didn’t I say most people go to the ends of the earth to hang on to life towards the end? Well, apparently not all. Why is this?

Several months ago, I had a relevant conversation with another close friend about how some people cling to life at the end no matter how much suffering and pain they endure, while others simply throw in the towel. We concluded it may have something to do with declining hormone levels. So I gave my anti-aging physician a call a few days ago to discuss this possibility. His response was that yes, declining hormone levels lead to depression, which usually translates to loss of appetite, and of course, a diminished will to live. He routinely reverses this phenomena with closely monitored hormone replacement therapy (HRT).

Could declining hormone levels be evolution’s way to nudge us into going quietly into the night? Could savvy docs reverse deteriorating attitudes and improve and extend millions of lives with simple HRT?

I think the answer is a resounding YES!

Saturday, I enjoyed a wonderful lunch get together with one of the most esteemed psychologists and authors in history. In fact, he has been one of my personal heroes for about 40 years. He’s now experiencing moments of forgetfulness which he calls his “senior moments”. The difference between him and my friend’s father is he is attacking his challenge head on, while maintaining his witty sense of humor. He’s getting sophisticated diagnostics, will undergo cutting edge treatment and is determined to reverse it.

And reverse it he will, according to a medical consultant who specializes in neurodegenerative conditions.

The moral to this story is, don’t wait until you see serious decline to see an anti-aging specialist. In fact, see one before you experience any decline – period. After all, once you see signs of a condition or disease, it may be too late. Heart disease and cancer are two good examples. They eat away at you for years before you show symptoms. And one symptom from heart disease is often sudden death.

Your perfect cure is prevention.
__________________________________
THREE DECADES FROM NOW

Under the present weight of regulation, it looks to take about 30 years for a new medical technology to progress from first proof of concept through to widespread and cost-effective availability - for those that aren't buried young by the cost of red tape, that is. Compare that with something more like 20 years in less regulated industries. That difference adds up. But what can we expect to see in the 2030s, based on what has taken place in laboratories and trials in the past few years?

http://www.fightaging.org/archives/001537.php

"Replacement organs will be grown to order from your own cells.
Stem cells will be created, manipulated, and transplanted to direct extraordinary regeneration.
Age-damaged immune systems will be wiped clean and replaced afresh.
Gene therapy will be a mature technology, and genetic disorders curable.
Everyone will know their DNA sequence, and have access to a vast database of knowledge that describes risks, therapies, and best practices.
Cancer will be detected early, and even late-stage metastasis cured with few side-effects by nanoparticle-based, viral, or other therapies.
The important mitochondrial DNA will be replaced when damaged by disease or age.
Many of the biochemical processes underlying the benefits of exercise, calorie restriction, and known human longevity-associated genes will be reproduced by cheap drugs.”

ON STEM CELLS AND AGING

While perusing PubMed Central, Reason discovered a good overview of present thinking on stem cells, stem cell niches, and their role in aging:

http://www.fightaging.org/archives/001536.php

"If many adult tissues and organs are continuously replenished by cells derived from stem cells, then why do they show signs of aging? One possibility is that stem cells themselves age and senesce, resulting in a decreased ability to replace worn-out progeny and/or the fact that they pass on aged phenotypes to their progeny.

NOTE: Pending modest funding, a stem cell company will soon be launched that could solve this problem within a couple of years.

Somewhere at the end of this road of investigation lies the means to keep stem cell populations vital while not exaggerating the risk of cancer due to runaway failure in a stem cell - the most likely reason we have evolved mechanisms that diminish stem cell activity in response to age-related biochemical damage. At some point, the large and well-funded field of regenerative medicine is going to turn its attention to repairing the damage of aging. Many major lines of research presently address age-related disease, and it is becoming clear that the effectiveness of therapies is hindered by age-related damage in stem cells and their niches. We should encourage research in this direction.
______________________________

LATEST HEALTHY LIFE EXTENSION HEADLINES

Towards Long Life and Happiness (August 01 2008) http://www.canada.com/components/print.aspx?id=924ef76b-5103-4aad-a596-13278777f8eb
From Canada.com: "Aging - and more specifically, the aspiration to slow human aging - is the most important neglected issue of our time. There are many things that could kill the world's current 6.5 billion plus people, but the vast majority of those currently alive today, especially in the developed world, will die from age-related causes. The diseases of aging could be the real scourge of the 21st century. That is, unless we do something to remedy the biological vulnerabilities we have inherited from our evolutionary history. The current approach to medical research is to tackle individual diseases, one at a time. So we spend large amounts of public funding on basic research into cancer, heart disease, diabetes, Alzheimer's, etc. But we invest very little in understanding the biology of aging and how it impacts our health prospects. Supplementing the current medical approach with one that also tackles aging would help us take a more inclusive approach to health extension. Even if we find a cure for one of the diseases of aging - like cancer - it would only extend life by a few years, as most people will likely be afflicted by one of the other diseases of aging. But if we could modify the biological mechanisms underlying aging, we may be able to significantly increase the number of disease-free years humans can expect to live. This would reap enormous individual and societal benefits."

Exercise in a Pill? (July 31 2008)
http://www.eurekalert.org/pub_releases/2008-07/si-eia072808.php
If researchers could reproduce the biochemical basis for the health and longevity-enhancing results of exercise, the resulting drug would no doubt be as popular as calorie restriction mimetics. Exercise and calorie restriction are the two gold-standard items for health: little else even comes close yet. From EurekAlert!, news of small steps on this path: Researchers "identified two signaling pathways that are activated in response to exercise and converge to dramatically increase endurance. Previous work with genetically engineered mice [had] revealed that permanently activating a genetic switch known as PPAR delta turned mice into indefatigable marathon runners. In addition to their super-endurance, the altered mice were resistant to weight gain, even when fed a high-fat diet that caused obesity in ordinary mice. On top of their lean and mean physique, their response to insulin improved, lowering levels of circulating glucose. We wanted to know whether a drug specific for PPAR delta would have the same beneficial effects."

Short Telomeres and Accelerated Aging (July 31 2008) http://newswire.rockefeller.edu/?page=engine&id=791
All of the rare accelerated aging conditions appear to be caused by one aspect of "normal" aging exaggerated and run wild to cause great biochemical damage. Researchers now think they understand what underlies another of these conditions: "Sufferers of the disease, called dyskeratosis congentia, tend to have problems in tissues in which cells multiply rapidly - skin, hair, nails, tongue, gut and bone marrow - and usually die between the ages of 16 and 50 from bone marrow failure, or the inability to replenish their blood cells. Each time a cell divides, the protective caps at the ends of chromosomes shorten - and when these caps are gone, so are we. Now, by using an unconventional strategy to shorten telomeres in mice, [researchers] have not only created the first faithful mouse model for studying [dyskeratosis congentia], but they have revealed the molecular defect behind the disease. These results suggest that in patients suffering from dyskeratosis congenita, the enzyme telomerase can't elongate telomeres as fast as the nucleases chew them away. Clearly, the next step is to understand how telomeres are degraded in human cells. We need to identify the nucleases at work and find out how they are regulated."

Reduced Protein Intake and Immune Response (July 30 2008) http://pmid.us/18656703
Scientists here demonstrate the connection between reduced dietary protein and a better immune response, already known from the practice of calorie
restriction: "Manipulation of dietary variables is one the most described events to retard the aging process and maintain immune function. The present study deals with the effect of variable dietary protein-carbohydrate ratios (without caloric restriction) on the alteration of immune response of male albino rats. These results thus suggest that diets with variable dietary protein-carbohydrate ratios act as an exogenous modulator of immune response with age and [a low protein] diet may be beneficial to slow down/reduce the impairment of immune response in aged individuals." For comparison, you might also look at studies of methionine restriction without overall calorie restriction. Greater control of diet over the years adds up, and every extra year of health gained can make a big difference when the pace of medical development is rapid.

The Tithonus Error (July 29 2008)
http://www.dailymail.co.uk/news/article-1038717/MAX-HASTINGS-Growing-old-Britain-happy-experience-The-longer-live-worse-quality-life-becomes.html
So many, many people still believe that the result of longevity science will be that you are older and ever more frail for more years, with no hope of death. This is absolutely false: the goals are in fact rejuvenation of the old, repair of the biochemical damage of aging, and the extension of healthy, youthful life. But still people have the fate of Tithonus in mind, sunk into the collective consciousness through a hundred similar cautionary tales. So you'll see this sort of doleful op-ed from the Daily Mail: "To some of us, [longevity] seems a ghastly prospect. I am 62, and find life terrific. I get more work done than ever before, because my children have long ago left home and I remain fit. I take pills to keep my blood pressure down and waterworks functioning. It seems to some of us terrifying to imagine that we might survive to 100. Surely, the drear misery and loneliness that accompanies such age is not worth it for a birthday party, telegram from the Queen and maybe a paragraph in the local newspaper. Once mobility is gone, once the simplest actions of daily life become dependent upon others, it is hard to sustain self-respect. If science indeed continues to lengthen our lives, I believe that we shall have to be given a choice about opting out." The work of advocacy and education must continue - this is a sign that much remains to be done.

Futurist Musings on the Leap Ahead (July 29 2008) http://www.canada.com/topics/bodyandhealth/story.html?id=fa35f402-d10e-4c1e-a8c9-cc3f1cc12f92
From Canada.com: "Genetic science, stem-cell research and extreme caloric restriction are all part of a burgeoning 'immortality industry' that could soon point the way to a fountain of youth with the potential to stretch the human life span to 125 or 150 years, says a sociologist and consultant on future studies. Advances such as nanotechnology - the emerging ability to manipulate extremely small structures - could ultimately make it possible to regenerate every cell in the body. At that point, we can throw out every idea we have about longevity and even mortality itself. The effects of human life-extension will be far-reaching, [potentially] spawning second or third careers in people's extra decades and a society of lifelong students using the gift of more time to continually reinvent themselves with new education. The extension of human life will also depend on people's lifestyle [and] the current obesity epidemic, smoking habits and other unhealthy behaviors indicate they don't always make beneficial choices. People can be 'seduced' by breakthroughs they believe will save them from themselves. I think there is going to be a tremendous chasm between average life expectancy and life potential."

Michael West at Aging 2008 (July 28 2008)
http://www.acceleratingfuture.com/people-blog/?p=2338
Another Aging 2008 transcript from Future Current: "I have been entranced by the immortality of the species and how it's accomplished. A simple way of putting it: we are made of cells, trillions of them, that have been proliferating backward in time all the way through hundreds of millions of years to the beginning of life on the planet, leaving no dead ancestors in their wake ever - or we would not be here. It is our somatic cells that are destined to die. All the cells in our body have this immortal legacy going backward in time millions of years and will face death for the first time ever in our lifetime. What can we learn about the immortality of the species to transport those observations and discoveries of modern technologies into something that will really do something about human aging? How could these cells be used in the next ten years? There are numerous examples I could give you, but one hopeful one - macular degeneration. This is the leading cause of blindness, due to the aging of our retina. These cells have now been made in a form that is appropriate to begin human clinical trials. When they become lost or dysfunctional in the back of the retina, they cause this cascade of pathology that is a leading cause of blindness in the elderly. It is at least one of the top targets for how we hope these cells will eventually be used in medicine."

Cryonics as an Elective Medical Procedure (July 28 2008) http://www.depressedmetabolism.com/2008/07/24/cryonics-as-an-elective-medical-procedure/
From Depressed Metabolism: "The limitation that cryonics procedures can only be started after pronouncement of legal death reflects the unfortunate fact that the current medical establishment does not recognize cryonics as a credible form of advanced critical care. As a result, cryonics is currently practiced as a form of emergency medicine in which conventional resuscitation technologies such as chest compressions and ventilations are used to avoid the kinds of injury that follow after cardiac arrest. Although there will always be a place for cryonics as a form of emergency medicine to treat cases of trauma and sudden circulatory arrest, most patients who currently present for human cryopreservation would benefit from more hospital cooperation in choosing cryonics as an elective medical procedure. Although current cryonics organizations such as Alcor try to make the best of a bad situation by employing standby teams that allow rapid intervention after cardiac arrest to reduce brain injury, much improved quality of care of cryonics patients would be possible if cryonics procedures would start at a point where medical professionals (with informed consent of the patient and/or family) would determine that further treatment of the patient with contemporary technologies would be futile, or even counter-productive."
______________________________

DISCLAIMER: News summaries are reported by third parties, and there is no guarantee of accuracy. This newsletter is not meant to substitute for your personal due diligence and is not to be taken as medical advice. For originating report, please see www.longevitymeme.org/newsletter/.

If you would like to be removed from my list, I will stop sending you Longevity News Digest if you simply reply to this email with Unsubscribe in the subject line.

Aging, the New Frontier

Dear Future Centenarian,
We are finally moving from an era where nothing could be done to defeat aging into an era where advancing technology will give us the tools to overcome it. All the old attitudes are no longer relevant.
We’re so used to people dying from age related causes that we accept it as a normal part of life. And we become desensitized to this death. But let’s look at it from a different angle and see if you think about it differently.
Robert Freitas, a brilliant scientist and perhaps the world’s utmost authority on Nanomedicine, offers some interesting ways to view aging. He points out the following:
100,000 lives are lost every single day from aging related causes. They’re scattered all over the world, so we hardly notice. But what if 400 jetliners fell out of the sky in a single day? We would be astonished, outraged and sickened. Yet effectively, that’s equivalent to 400 jetliner crashes.
If 400 planes crashed every day, wouldn’t the world marshal all its powers to insure aircraft safety, especially if we had no choice but to fly?
What if we could avoid… or at least postpone most aging related deaths?
Then why isn’t treating aging a #1 priority?
After all, if you or a loved one had a major medical condition such as cancer, heart disease or suffered a stroke, wouldn’t you ask for the very best medical care?
If we had a treatment that could reverse Alzheimer’s, Parkinson’s, osteoporosis, arteriosclerosis or diabetes… who in their right mind would turn it down?
Now it is aging, the new frontier. Since it kills everyone who survives or dodges diseases, might not aging be considered a disease as well? MaxLife looks at it as a curable disease, in fact the mother of most diseases. And we’re determined to do something about it.
_____________________________
LATEST HEALTHY LIFE EXTENSION HEADLINES

The Dreaded Reactive Oxygen Species (July 25 2008) http://www.eurekalert.org/pub_releases/2008-07/uorm-ruk072108.php
It's good to see more research groups looking into targeting antioxidants to the mitochondria. From EurekAlert!: "Researchers have taken a first snapshot of how a class of highly reactive molecules inflicts cellular damage as part of aging, heart disease, stroke, cancer, diabetes, kidney disease and Alzheimer's disease to name a few. Researchers have discovered a tool that can monitor related damage and determine the degree to which antioxidant drugs effectively combat disease. Our study provides a better glimpse of why a cell under assault by disease makes 10 times as many reactive oxygen species [ROS] as the same cell when healthy. We have discovered a chemical tool for investigating how diseases cause damage, mitochondrion by mitochondrion. Efforts to develop antioxidant drugs (e.g. vitamin E) to treat diseases of increased oxidative stress have met with limited success to date because they tried to eliminate ROS, rather than maintain the right amount, Sheu said. He established the Mitochondrial Research & Innovation Group (MRIG) [in] 2002 with the goal of designing therapies to deliver precise amounts of antioxidants to the mitochondria of diseased cells only. MRIG teams are, for example, screening through compounds to confirm that oxidative stress can be reversed by mitochondria-specific drugs."

On Hormesis and Longevity (July 24 2008) http://pmid.us/18648625
A nice overview of hormesis: "Aging is characterized by a stochastic accumulation of molecular damage, progressive failure of maintenance and repair, and consequent onset of age-related diseases. Applying hormesis in aging research and therapy is based on the principle of stimulation of maintenance and repair pathways by repeated exposure to mild stress. In a series of experimental studies we have shown that repetitive mild heat stress has anti-aging hormetic effects on growth and various other cellular and biochemical characteristics of human skin fibroblasts undergoing aging in vitro. These effects include the maintenance of stress protein profiles, reduction in the accumulation of oxidatively and glycoxidatively damaged proteins, stimulation of the proteasomal activities for the degradation of abnormal proteins, improved cellular resistance to ethanol, hydrogenperoxide and ultraviolet-B rays, and enhanced levels of various antioxidant enzymes. Anti-aging hormetic effects of mild heat shock appear to be facilitated by reducing protein damage and protein aggregation by activating internal antioxidant, repair and degradation processes."

Yeast and Aging Research (July 22 2008) http://ouroboros.wordpress.com/2008/07/21/biogerontology-rising-recent-progress-in-yeast-aging-research/
Ouroboros looks at the humble yeast in context: "Our understanding of aging in animals owes a great debt to a large body of careful work in a single-celled organism, the brewer's yeast Saccharomyces cerevisiae. Indeed, as I've argued before, yeast is one of the two organisms with the strongest credible claim to have started modern biogerontology. An unusually large crop of yeast aging papers have appeared over the last few months, and I thought it would be appropriate to spend a few paragraphs describing them - in honor of this humble organism that rises our bread, ferments our beer, and has done so much to open our eyes to the fundamental mechanisms of aging. Yeast mutants in worm longevity genes are significantly more likely to be long-lived than randomly chosen mutants - suggesting [that] genes that modulate aging have been conserved not only in sequence, but also in function, over a billion years of evolution. Given this functional conservation, it is reasonable to use yeast to help answer questions about aging in general, so long as these questions as cell-biological in scope."

New York Times on Sirtris (July 22 2008) http://www.nytimes.com/2008/07/22/health/research/22long.html?pagewanted=all
The New York Times looks at Sirtris Pharmaceuticals: "The hope is that activating sirtuins in people would, like a calorically restricted diet in mice, avert degenerative diseases of aging like diabetes, heart disease, cancer and Alzheimer's. There is no Food and Drug Administration category for longevity drugs, so if the company is to submit a drug for approval, it needs to be for a specific disease. Nonetheless, longevity is what has motivated the researchers and what makes the drugs potentially so appealing. Dr. Christoph Westphal, the chief executive of Sirtris, said of the potential of the drugs, 'I think that if we are right, this could extend life span by 5 or 10 percent.' He added that his goal was to develop drugs against specific diseases, with the extension of life being 'almost a side effect of our medicine.'" There you have the most serious problem facing longevity science today: that its direct application is not permitted by the FDA. Until this changes no serious investment will be made in the US to bring longevity science to the clinic. This is a tragedy of so great a scale as to beggar belief.

Thoughts on Mortality and Its Evasion (July 21 2008) http://tacit.livejournal.com/250032.html
An interesting LiveJournal post: "A person immune to the ravages of old age would still not be immune to death; accident, violence, and other misadventure is perfectly capable of ending even a 25-year-old's life. It simply means that person no longer has a cap on the maximum time he can live, if he so chooses. And that's really what it's all about. Choice. If you go into the doctor's office, and he tells you that you have a bacterial infection, which will slowly grow progressively worse until it kills you painfully, then offers you an antibiotic pill that will completely eradicate the infection, I bet you'll take it. Even if you don't fancy the thought of living forever. There's an important point in that.

Even folks who don't much want to live forever still probably don't want to die today. Or tomorrow. Someday, perhaps, if that 'someday' is held in the abstract; some future time when things no longer seem interesting. But not today. And that's the point. A solution for aging puts the power to choose in your hands. Old age forces your hand; you don't get the choice to see your grandkids graduate from school, or to celebrate your fiftieth anniversary. The choice is made for you. And I don't see how that benefits anyone."

Growing Blood Vessels (July 21 2008) http://news.bbc.co.uk/2/hi/health/7514317.stm
Researchers continue to work at the blood vessel problem in tissue engineering. From the BBC: "Scientists have used human cells to grow new blood vessels in a mouse for the first time. The ability to develop swiftly a new network of tiny blood vessels - known as capillaries - would be a prize for scientists. There are dozens of potential applications in medicine, particularly in the treatment of conditions which involve damage to a tissue's blood supply, such as that to the heart muscle following a heart attack. However, the complex structure of these vessels has slowed progress. What's really significant about our study is that we are using human cells that can be obtained from blood or bone marrow rather than removing and using fully developed blood vessels. It could certainly assist in the connection of other engineered organs to the body's blood supply. Although this approach is not yet suitable for clinical use, it is interesting that they have demonstrated you have all the elements you need to create a functional network of capillaries from a small amount of blood."
______________________________

DISCLAIMER: News summaries are reported by third parties, and there is no guarantee of accuracy. This newsletter is not meant to substitute for your personal due diligence and is not to be taken as medical advice. For originating report, please see www.longevitymeme.org/newsletter/.
If you would like to be removed from my list, I will stop sending you Longevity News Digest if you simply reply to this email with Unsubscribe in the subject line.

Biological Evolution

Dear Future Centenarian,
We’ve come a long way in our lifetimes. In fact, we have accomplished as much then as we did in all of recorded history. At least technologically. As a race, we really didn’t seem to have learned many lessons. Oh sure, maybe our justice systems are a little more fair (and maybe not), we may have developed a little more tolerance and compassion, and maybe we’re not quite as barbaric. All in all though, we react to intrusions about the same as prehistoric man.
We still settle disputes and differences about the same way. We either initiate or answer with violence for the most part. But instead of clubbing each other senseless and confining our rage, jealousies, pettiness and intolerances to an area roughly equivalent to our immediate reach and to one enemy or victim at a time, we now have these wonders of science at our disposal, capable of inflicting widespread death and destruction.
Then, we had clubs and primitive minds. Now we have nukes, biological and chemical weapons, potentially devastating nanotechnology capabilities… and primitive minds.
While we have evolved in some ways at light speed, our ability to solve social problems and disputes and our tendency to hate hasn’t changed since caveman days. Look, we’re on the cusp of breaking through to indefinite lifespans and solutions for health problems, poverty and pollution. But what good does it do us when emotionally unstable individuals have abilities to wipe out millions with no more effort or forethought than swinging a club?
Fortunately, the human race is extremely resilient and resourceful. We often respond to challenges in creative and unexpected ways. A relatively new foundation recognizes this challenge and is taking it on as part of its agenda. See more information at www.InnerSpaceFoundation.org.
They recognize that biological evolution is a somewhat haphazard and non-optimizing process that has produced many undesirable artifacts. Among a large number and wide variety of such artifacts, two stand out as the underlying causes of the most pervasive and extreme human suffering: mental and lifespan limitations. Mental inabilities, including the failure to resolve conflicts non-violently, are universal. They must ultimately serve to explain our ongoing failures to end human warfare, crime, poverty, and famine, and to completely cure diseases, disabilities, aging and death. Therefore, these inabilities are fundamentally even more harmful to humanity than the categories of biomedical dysfunction we currently labor to cure.
This belief forms the core of the Bioprogressive philosophy. The overall goal of the InnerSpace Foundation (IF) is to accelerate developing biomedical technologies for transcending these limitations. IF is taking specific steps toward enhancing memory, learning and cognition. These near-term goals should ultimately help us to eliminate or transcend other unwanted artifacts of Darwinian evolution.
IF, among others, have longer-term goals aimed at preserving memories. So hang on. We have some interesting times ahead.
____________________________________
CANCER AND IMMUNE SYSTEM PROFICIENCY

Are some immune systems much better than others at destroying cancer in its earliest stages? It seems that this is the case. Can we copy that proficiency and use it as a therapy? The prospects look promising:

http://www.fightaging.org/archives/001525.php

"First, we had cancer-resistant mice and asked, 'What can we learn from it?' The reason it's resistant is because it has very different white cells. So then that immediately prompted the concept of therapy, because you can easily transfer white cells. You can extract them as a therapeutic agent and give them to another mouse. It's a therapy. It's much better than to find the gene. If you find the gene, then you have to understand the mechanism, and you have to find a way to put the gene into the cell, into all the cells you want to, and that would not work very easily. The technology as we speak right now is not really mature for that area. You might have to wait another 10, 20 years before that technology catches up with the concept. However, what we found is a cell as a therapeutic agent, so why not go ahead and see how it works. It worked really well in mice, so the next question, very obviously, is can we find a similar cancer resistance for humans as a donor for a therapeutic agent. And the answer is yes, we did find quite a few of them ".

From a broad assessment of cutting edge cancer research, it seems that we are well on the way to turning cancer into a controllable chronic illness. You'll have outbreaks, they'll be caught early, and the medicine of the 2020s will eliminate them. The question is whether this is good enough: is a comprehensive suite of low-risk, safe cancer cures enough to remove cancer as a threat while our lives are extended by other medical technologies?
______________________________

LATEST HEALTHY LIFE EXTENSION HEADLINES

The Broadening Search for Longevity Genes (July 17 2008)
http://www.technologyreview.com/printer_friendly_article.aspx?id=21092
The MIT Technology Review looks at continued attempts to understand the degree to which present healthy human longevity is influenced by genes: "An ambitious plan to sequence 100 genes in 1,000 healthy old people could shed light on genetic variations that insulate some people from the ailments of aging, including heart disease, cancer, and diabetes, allowing them to live a healthy life into their eighties and beyond. Rather than focusing on genetic variations that increase risk for disease, scientists plan to focus on genes that have previously been linked to health and longevity. Advances in genetic screening technologies have allowed scientists to start searching the genome for clues to healthy aging and a lengthy life span. That work has revealed that the genomes of healthy old people are not blemish free. These people have genetic susceptibility markers for many serious diseases [but] they don't get any of these diseases. What is the explanation? What might account for their insulation from these diseases?" Genes are not fate - evidence to date suggests that lifestyle choices have much more weight for all but the most genetically unlucky, and those choices are reflected in epigenetic variations, not genetic variations.

Self-Assembly in Tissue Engineering (July 16 2008) http://www.technologyreview.com/printer_friendly_article.aspx?id=21080
The MIT Technology Review looks at a promising strategy in tissue engineering: "Tissue engineers are ambitious. If they had their way, a dialysis patient could receive a new kidney made in the lab from his own cells, instead of waiting for a donor organ that his immune system might reject. Likewise, a diabetic could, with grafts of lab-made pancreatic tissue, be given the ability to make insulin again. But tissue engineering has stalled in part because bioengineers haven't been able to replicate the structural complexity of human tissues. Now researchers have taken an important first step toward building complex tissues from the bottom up by creating what they call living Legos. These building blocks, biofriendly gels of various shapes studded with cells, can self-assemble into complex structures resembling those found in tissues. This will be an effective way to put the cells where we want them to be. You can probably generate a tissue with a higher complexity [using] the new method than is possible with a scaffold that has to be seeded with cells." Compare and contrast with the use of whole-organ cell matrix templates, another recent development aimed at solving the same problem.

Stress, Cortisol, and Shortened Telomeres (July 16 2008) http://www.eurekalert.org/pub_releases/2008-07/uoc--usi071508.php
Chronic stress correlates with shorter telomeres, as well as with worse health. Via EurekAlert! researchers are proposing a mechanism by which telomere length is reduced by stress, leading to a worse immune response: "Short telomeres are linked to a range of human diseases, including HIV, osteoporosis, heart disease and aging. An enzyme [called telomerase] keeps immune cells young by preserving their telomere length and ability to continue dividing. The stress hormone cortisol suppresses immune cells' ability to activate their telomerase. This may explain why the cells of persons under chronic stress have shorter telomeres. When the body is under stress, it boosts production of cortisol to support a 'fight or flight' response. If the hormone remains elevated in the bloodstream for long periods of time, though, it wears down the immune system. We are testing therapeutic ways of enhancing telomerase levels to help the immune system ward off cortisol's effect. If we're successful, one day a pill may exist to strengthen the immune system's ability to weather chronic emotional stress."

Why Fight Aging? (July 15 2008)
http://www.acceleratingfuture.com/people-blog/?p=2307
A Future Current transcript of one of Aubrey de Grey's presentations at Aging 2008: "Some people say, 'I don't want to live to a thousand.' I don't want to live to a thousand, necessarily. I don't even know if I want to live to a hundred. But I do know I want to make that choice when I am 99, rather than having it gradually removed from me by declining health. This is what it comes down to. The extension of lifespan by the defeat of aging is not the point - at least it is not the main point for me, and I do not think it is the main point for most people who are engaged in this crusade. The purpose is to alleviate the suffering that goes with getting decrepit, frail and dependent. Of course, this includes not just those who are suffering that, but the suffering of their loved ones. The extension of average lifespan is essentially a side benefit. It is something that will happen because the way that we are going to do this, using regenerative medicine, will also mean that you have only the same probability you did when you were a young adult of dying peacefully in your sleep without any of these diseases. In other words, a very low probability indeed. You will indeed on average live a great deal longer, and I don't think you’ll complain if you do. However, that is not the purpose. The purpose is to alleviate suffering."

On the Way to Longevity (July 14 2008)
http://www.dailybruin.ucla.edu/news/2008/jul/14/within-20-years-you-wont-have-grow-old/
The Daily Bruin talks to some of the folk who were at Aging 2008: "Defeating the effects of time by finding a cure for aging has become the focus of multiple areas of research, bringing the possibilities of achieving immortality from fantasy into the realm of science. The new possibilities offered by regenerative medicine illustrate how advancements in therapy on the molecular and cellular level may be able to extend the healthy human life span within the next 20 years. Finding a cure for aging is no longer a theoretical target or a fantasy, but on the way to becoming a practical target. Aging is the most universal degenerative condition and is now becoming the target of regenerative medicine. The body is a really complicated machine, but it's still a machine, so its healthy lifespan can be extended indefinitely by sufficiently comprehensive repair and maintenance, just like simple man-made machines. Aging is a complex phenomenon that affects many different systems. Understanding it and fixing the damage as it comes can potentially cure the harmful effects of aging and as a result, elongate the healthy human lifespan."
______________________________

DISCLAIMER: News summaries are reported by third parties, and there is no guarantee of accuracy. This newsletter is not meant to substitute for your personal due diligence and is not to be taken as medical advice. For originating report, please see www.longevitymeme.org/newsletter/.

If you would like to be removed from my list, I will stop sending you Longevity News Digest if you simply reply to this email with Unsubscribe in the subject line.

David A. Kekich
Maximum Life Foundation
714-641-0700/Fax 714-464-4135
www.MaxLife.org

"Where Biotech, Infotech and Nanotech
Meet to Reverse Aging by 2029"

The Problem… Population Size. The Solution… SuperLongevity

Can super longevity solve, rather than create a population problem?

Consider these points edited from a paper presented several weeks ago by Herb Meyer at the World Economic Forum in Davos, Switzerland. Mr. Meyer is widely credited with being the first senior U.S. Government official to forecast the Soviet Union's collapse, for which he later was awarded the U.S. National Intelligence Distinguished Service Medal, the intelligence community's highest honor. Formerly an associate editor of FORTUNE, he is also the author of several books.

Some of His Conclusions

Maintaining a steady population requires a birth rate of 2.1. In Western Europe, the birth rate currently stands at 1.5, or 30 percent below replacement. In 30 years there will be 70 to 80 million fewer Europeans than there are today. The current birth rate in Germany is 1.3. Italy and Spain are even lower at 1.2. At that rate, the working age population declines by 30 percent in 20 years, which has a huge impact on the economy. When you don't have young workers to replace the older ones, you have to import them.

In Japan, the birthrate is 1.3. As a result, Japan will lose up to 60 million people over the next 30 years. Because Japan has a very different society than Europe, they refuse to import workers. Instead, they are just shutting down. Japan has already closed 2,000 schools, and is closing them down at the rate of 300 per year. Japan is also aging very rapidly. By 2020, one out of every five Japanese will be at least 70 years old.

The birth rate in Russia is so low that by 2050 their population will be smaller than that of Yemen.

Nobody has any idea about how to run an economy with those demographics. Europe and Japan, which comprise two of the world's major economic engines, aren't merely in recession, they're shutting down. This will have a huge impact on the world economy, and it is already beginning to happen.

When the birth rate drops below replacement, the population ages. With fewer working people to support more retired people, it puts a crushing tax burden on the smaller group of working age people. As a result, young people delay marriage and having a family. Once this trend starts, the downward spiral only gets worse.

These countries have abandoned all the traditions they formerly held in regard to having families and raising children. The U.S. birth rate is 2.0, just below replacement. We have an increase in population because of immigration. When broken down by ethnicity, the Anglo birth rate is 1.6 (same as France) while the Hispanic birth rate is 2.7.

In the U.S., the baby boomers are starting to retire in massive numbers. This will push the elder dependency ratio from 19 to 38 over the next 10 to 15 years. This is not as bad as Europe, but still represents the same kind of trend.

The world's most effective birth control device is money. As society creates a middle class and women move into the workforce, birth rates drop. Having large families is incompatible with middle class living. The quickest way to drop the birth rate is through rapid economic development.

Pretty sobering, isn’t it? So what’s the solution? Longevity… and lots of it. Keep the elderly alive, healthy and productive. Keep them out of retirement, hospitals and nursing homes where they drain resources, and have them contribute to the economy when they are at the peak of their productive capacity.

Network Your Way to Immortality

Dear Future Centenarian,

Saturday evening, I enjoyed life extension and stem cell technology conversation and dinner at an incredible couple’s home. Their guests were incredible as well. Not only were they bright, well informed and enthusiastic about extreme life extension, but they were a mix of savvy and successful scientists and business people. The latter will have as much to do with your longevity as the former. Maybe more. You’ll see what I mean when you read the attached PowerPoint.

Since 2000, Maximum Life Foundation designed a scientific and financial roadmap to reverse the human aging process. The attachment illustrates an aggressive approach to solving aging in your lifetime. You’ll notice what a surprisingly small investment we think it will take. But we can back up our scientific and financial assumptions. Now it’s time to implement the plan.

Another Life Extension Report from Longevity Meme

Dear Future Centenarian,

See http://www.longevitymeme.org/newsletter/.

We’re seeing some serious progress in life extension research. Here are two projects that were announced at Aubrey de Grey’s SENS Conference last week:

http://blog.methuselahfoundation.org/2007/09/sens3_report_towards_mitochond_1.html

"Unlike most other parts of the cell, mitochondria house many of the genes encoding their essential proteins within themselves. These genes are vulnerable to the constant assault of free radicals produced by the mitochondria as a side-effect of their role as cellular power plants. When mitochondrial DNA is damaged, it cannot make the proteins needed to carry on the essential business of generating energy for the cell; the ensuing metabolic damage is the driver of age-related rise in oxidative stress. This oxidative stress fuels free radical damage and interferes with essential signaling pathways in cells far from the original site of the damage.

"PhD candidate Mark Hamalainen of Cambridge University presented the initial success in his Methuselah Foundation-funded work on allotopic expression, showing evidence that his allotopically-expressed genes could encode the relevant proteins and that these were taken up into the mitochondria. In this case, the genes encode healthy and defective versions of the protein that is miscoded in Neuropathy, Ataxia and Retinitis Pigmentosa (NARP), a hereditary mitochondrial disease characterized by blindness and weak and uncoordinated muscles. Well done! It is good to see Foundation-funded research make such solid progress; many thanks go to the generous donors who have made this possible."

http://blog.methuselahfoundation.org/2007/09/sens3_report_the_gift_versus_c_1.html

"In 2003, Dr. Zheng Cui and his colleagues at the Comprehensive Cancer Center of Wake Forest University reported the discovery of mice with immune cells that rendered them invulnerable to cancer. Last year, Dr. Cui electrified the world when he showed that the new strain's cancer-fighting abilities were caused by a particular subset of their immune cells -- members of a class of white blood cell known as neutrophil granulocytes. These cells are from the innate immune system, meaning that they don't have to 'learn' to identify a narrowly-defined enemy, but are constantly on the lookout for broadly-defined 'foreign' cells.

"At SENS3, Dr. Cui presented the next logical step in his research: work demonstrating the existence of, and characterizing, high-potency cancer-killing granulocytes in humans."

The Inevitability of Open-Ended Lifespans

Dear Future Centenarian,

Here’s an excellent commentary from Reason at LongevityMeme.org:

“The choice of living a healthy, youthful life of centuries and more is inevitable. That much is obvious, written in the present breadth of human civilization, knowledge of what is possible under the laws of physics, and pace of progress in biotechnology. The burning question in this case is whether or not it will happen soon enough to benefit you reading this today:

Replacement biological organs are a decade away, and commercial efforts to develop sophisticated repairs to age-damaged cells and vital biomechanisms will be rife in the 2020s. Computational power will be so great and so cheap that tens of thousands and then millions of research programs will be accomplished in simulation for a tiny fraction of their cost today; the priesthood of bioscience will dissolve and progress will be as diverse, energetic and imaginative as it is for open source software at present. Redesigning human biochemistry and greatly augmenting our biology with nanomachinery will be hot areas for venture funding.

I see development of the baseline technologies required for greatly extending the healthy human life span as a given for the next few decades. The biotechnology revolution is roaring ahead, and there's no halting the relentless advance of computational power. But just because we can doesn't mean we will - there is still the need to take that baseline technology and turn it to a desired use.

Given that there is no massive, serious life extension research and development community in existence today - and here, I'm thinking of a community to match the cancer research establishment in breadth and support - the future we'd like to see is still in doubt. If we want the awe-inspiring biotechnologies of the 2020s promptly put to use in repairing the damage of aging, right out of the starting gate, then we'd better get working on that now.”

Another Life Extension Report from Longevity Meme

Dear Future Centenarian,

See http://www.longevitymeme.org/newsletter/.

We’re seeing some serious progress in life extension research. Here are two projects that were announced at Aubrey de Grey’s SENS Conference last week:

http://blog.methuselahfoundation.org/2007/09/sens3_report_towards_mitochond_1.html

"Unlike most other parts of the cell, mitochondria house many of the genes encoding their essential proteins within themselves. These genes are vulnerable to the constant assault of free radicals produced by the mitochondria as a side-effect of their role as cellular power plants. When mitochondrial DNA is damaged, it cannot make the proteins needed to carry on the essential business of generating energy for the cell; the ensuing metabolic damage is the driver of age-related rise in oxidative stress. This oxidative stress fuels free radical damage and interferes with essential signaling pathways in cells far from the original site of the damage.

"PhD candidate Mark Hamalainen of Cambridge University presented the initial success in his Methuselah Foundation-funded work on allotopic expression, showing evidence that his allotopically-expressed genes could encode the relevant proteins and that these were taken up into the mitochondria. In this case, the genes encode healthy and defective versions of the protein that is miscoded in Neuropathy, Ataxia and Retinitis Pigmentosa (NARP), a hereditary mitochondrial disease characterized by blindness and weak and uncoordinated muscles. Well done! It is good to see Foundation-funded research make such solid progress; many thanks go to the generous donors who have made this possible."

http://blog.methuselahfoundation.org/2007/09/sens3_report_the_gift_versus_c_1.html

"In 2003, Dr. Zheng Cui and his colleagues at the Comprehensive Cancer Center of Wake Forest University reported the discovery of mice with immune cells that rendered them invulnerable to cancer. Last year, Dr. Cui electrified the world when he showed that the new strain's cancer-fighting abilities were caused by a particular subset of their immune cells -- members of a class of white blood cell known as neutrophil granulocytes. These cells are from the innate immune system, meaning that they don't have to 'learn' to identify a narrowly-defined enemy, but are constantly on the lookout for broadly-defined 'foreign' cells.

"At SENS3, Dr. Cui presented the next logical step in his research: work demonstrating the existence of, and characterizing, high-potency cancer-killing granulocytes in humans."

Life is Everything. Death is Nothing

Dear Future Centenarian,

To seek to provide the choice of healthy longevity for all who want it is an aspect of the better side of human nature:

http://www.fightaging.org/archives/001254.php

"Helping to make life longer and better, one action at a time, is a core human ideal. There are no special cases, no magical transition point at which it's fine and dandy to write people off or justify their deaths.

Healthy life extension flows quite naturally from the same mindset that helps neighbors and appreciates modern medicine. We all recognize that which is unpleasant in commonplace life, and it's only natural to work to remove that unpleasantness. Seeking equality of opportunity by helping people to overcome the limitations of their own personal human condition is a worthy goal today, and will be just as much so in a future of far greater opportunity. The foundation of opportunity is life - is being alive, and possessed of the vigor to take advantage of that fact. Without that, there is nothing. So I think we really have to start there, with aging, a great injustice blindly inflicted upon humanity by chance, physics and evolution.

To not seek the cure for aging would be just as strange as to fail to seek a cure for cancer or Alzheimer's - it would be inhuman and unnatural for the species that helps its neighbors and appreciates the good things in life."

What is Your Life Worth… Really?

Dear Future Centenarian,

If you knew technologies over the next few decades could deliver to you a chance for an open-ended youthful lifespan, how much would you donate to the research?

Say you want to live a much longer, healthier life. Would you help to achieve that goal by donating 90% of your net worth in support of research? If so, when? When you are terminally ill when it would probably be too late? Years or decades down the road? How about now? If not, how much?

There are no right answers in consideration of personal economic choices, but these are question you might ask yourself. Wealth at any level is worthless to the dead, and being alive and healthy allows you to generate more wealth. Logically we should all be willing to devote most of our net worth to longevity research at the most effective time. If we can buy time with money - and we can begin to now in earnest, for the first time in history, by supporting the research that will lead to the first healthy life extension medicine - then we should all be in that market.

MaxLife believes the tiniest fraction of most wealthy individuals’ net worth or annual income could reverse aging in less than 30 years. It also believes most of the money could be invested… not donated… in for-profit enterprises. More on this topic in a week or two.

Who Doesn’t Want to Live Longer?

Dear Future Centenarian,

Casual deathists are everywhere. I'm sure you all know someone who responds to the concept of healthy life extension with "I can't see why anyone would want to live past 100." This is what they have been taught throughout their lives, implicit in the way their peers and parents plan, act and talk. Perhaps "learned deathism" is a better term. A longevity revolution is right around the corner, yet we structure our lives in the same way our grandparents did:

There's nothing wrong with choosing not to strive for more healthy life, but I believe it's our responsibility to at least point out the lazy assumptions and false information that forms the basis of most casual deathism. Kevin Perrott, organizer of the Edmonton Aging Symposium, recently did a sterling job of this in a letter to the Globe and Mail, reproduced in this Fight Aging! post:

http://www.fightaging.org/archives/001332.php

For Reversing Aging, SENS Makes Sense

Dear Future Centenarian,

Where has summer gone? For that matter, where have the past few years gone? Days, weeks, months and years fly by too quickly now. What did you do this past year to help insure your longevity? You most likely belong to the last generation to die “on time”, or you will be part of the first generation to escape death for aging. It’s partly your choice.

A few days ago, I started reading Aubrey de Grey’s new book, Ending Aging: The Rejuvenation Breakthroughs That Could Reverse Human Aging in Our Lifetime. If you want an education on what causes aging damage and how to fix it, I suggest you get a copy. It is fascinating, and it could help you help yourself to extreme life extension.

Go to http://www.amazon.com/Ending-Aging-Rejuvenation-Breakthroughs-Lifetime/dp/0312367066.

With Friends Like This…

Dear Future Centenarian,

Admittedly, I’m a wild eyed optimist, especially regarding the prospects of indefinite youthful lifespans for you and me. But since I KNOW I’m an optimist, I try to take special efforts to see and understand pessimists’ points of view. Ten I try to balance the input and come to my own conclusions. In other words, I try to be objective about what our chances really are. I sent you my timeline and budgetary estimates several issues ago and stand by them.

So here’s an opinion from one who may be the most pessimistic of all well known gerontologists, followed by Reason’s commentary:

http://www.fightaging.org/archives/001354.php

"'We're all going to croak,' says Richard Sprott, the Ellison Medical Foundation's director, who expects that humans may eventually live as much as 30 years longer, but only in the distant future."

Read the full post; I find it incredible that anyone with Sprott's background can stand in the midst of the present outright revolution, of wild, foaming progress in bioscience, and say that things just aren't going to change all that much. It's an outlandish position - and an outlandish position held by someone who directs a fair amount of funding for aging research:

http://www.fightaging.org/archives/001331.php

It's a sad state of affairs we're in, wherein so much of the research establishment has declared defeat and stasis before even setting goals for aging science. How is it that we have an establishment community disbursing so much in the way of funds to exactly the people who are not going to make significant progress - those who say that progress is impossible or far distant in advance of any initiative?

The advance of science and technology is change itself, is the growth of opportunity and choice, and is the opening of new doors in the halls of the human condition. The hidebound and defeatist are not really contributing - if you want things done, if you want bold new progress, fund the people willing to set goals and shake trees.


NOTE: Sprott’s stance makes we want to toss my cookies. Everyone is entitled to an opinion. In his case though, I believe it will cost lives. Lots of lives. I say that not only because he may control more of the scarce “life extension” funding than almost all the administrators and researchers in the free market combined… but also because he is influential. With 100,000 people dying every day from aging, the last thing we need is anyone standing in the way of those who refuse to “go silently into the night”.

If someone were drowning and a lifeguard stood in the way of a would-be rescuer, what would you call the lifeguard? Multiply that by millions.