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.
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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.
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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?
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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
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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.
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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.
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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.
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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.
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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.

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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."

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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.

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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"

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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 researc