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."

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."

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.

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.

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.”

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.