Aging is Slowly Stealing Our Lives

You and I are both aware that aging is slowly stealing our health, our vigor and our lives. Yet we function without a sense of urgency to do something about aging. Why? Because we’re bombarded with our personal and career responsibilities and daily distractions. And those squeaky wheels are what get our attention. This is totally normal and logical. We have to take care of our families, get our haircuts and pay attention to endless details. Who has time to really make a commitment to being proactive when it comes to something as abstract as age-reversal?

That’s the way I used to think. But taking paths of least resistance normally leads us down reactive paths. In other words, we usually let outside forces control our lives. It isn’t until we’re faced with a crisis that those forces take a backseat to focusing on something that may have been avoided in the first place. Sometimes, that crisis means life or death.

This really hit home when I just found out a close and loved associate was diagnosed with one of the deadliest forms of cancer. What’s even more tragic is he’s an active life extension researcher. That’s the worst of ironies.

I am saddened to report that Dr. Chris Heward, one of the original participants of MaxLife’s first international scientific brainstorm sessions to reverse aging, is fighting an uphill battle for his life. Chris is Director of the Kronos Science Laboratories of Phoenix, AZ. He has been diagnosed with terminal, Stage-IV Esophageal Cancer. The cancer has metastasized to several other organs, and consequently his condition has a poor prognosis (50% mortality in 90 days and about 99% in a year).

Since surgery is no longer a realistic option, Chris has proposed to undergo an experimental but very promising immunotherapy treatment in Boca Raton, FL. However, this treatment requires blood donors less than 30 years old with "A" or "O" positive or negative blood types and no prior history of cancer in their families. If you are in—or if you know anyone in this category who would be willing to donate several units of blood to retrieve the granulocyte cells, please get in touch with me as soon as possible. Not only could this experimental treatment save Chris, but it could lead to a universal cure for many types of cancer. Here’s an opportunity to contribute to a great cause that could ultimately save many lives by making a simple referral.

Thank you in advance for your attention to this critical matter.
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LATEST HEALTHY LIFE EXTENSION HEADLINES

Researchers on Aging (November 14 2008) http://www.mcclatchydc.com/226/story/55835.html
An article of quotes from various noted aging reseachers: "Aging is caused by the gradual, lifelong accumulation of a wide variety of molecular and cellular damage. The free radical theory is the most widely accepted theory of aging. But the idea that aging is caused by one thing is naive. One general theory can never fit all. Clearly, it's the combination of genes that your parents dealt you and the lifestyle choices you make and the environmental toxins one is exposed to. One need only count the number of ways a car will fail to start to appreciate that aging can be caused by a large number of problems. Like any machine, it's going to wear out. About 25 percent of how a person ages is due to inherited genes. Certain genes control a cell's ability to repair damaged DNA. If those genes are defective, they can't do their job. Not everybody will be susceptible to diseases like Parkinson's or cancer as they age. But each one of us will lose muscle mass and muscle strength. That's why this research is so important. Frailty affects all of us."

Enhanced Longevity through Telomerase (November 14 2008) http://www.sciencenews.org/view/generic/id/38552/title/Telomere_enzyme_a_likely_key_to_longevity
From Science News: "the enzyme telomerase can extend the lifespan of mice by about 24 percent. Telomerase lengthens telomeres - the 'caps' on the end of chromosomes that protect DNA from damage. Like burning fuses, telomeres normally get shorter each time that most body cells divide. While the enzyme enables cells to keep dividing, it also takes cells one step closer to growing and proliferating out of control - that is, becoming cancerous. Lab animals with extra genes for telomerase often die young from tumors. [researchers] engineered mice to have not only an extra copy of the gene for telomerase, but also extra anti-tumor genes to combat the enzyme's cancer-causing potential. In the altered mice, signs of aging such as poor coordination or degraded tissue health were delayed compared to mice that had only the extra copies of anti-tumor genes." Most interesting; you might also want to look at recent research that suggests telomerase operates by protecting mitochondria, and less damaged mitochondria means better preservation of telomeres - but, more importantly for life span, less oxidative stress.

Better Synthetic Cartilage (November 13 2008) http://www.sciencedaily.com/releases/2008/11/081113075959.htm
From ScienceDaily: "Until now, creating synthetic cartilage was complex but not impossible. The problem was that it was impossible to imitate the perfection of human cartilage due to the difficulty in orienting the collagen nanofibers [in] a particular configuration: in parallel, in a circle, or crossed. The fibers that form the cartilage that protects the knee are aligned in parallel. [Researchers have now] achieved this using the electrospinning method. Collagen nanofibers are obtained by exposing the collagen to electrical discharges. The collagen is extruded, in the form of a nanofiber thread, through a fine needle and is deposited on an electric collector consisting of two grounded plates. The student placed a nonconductive material between the two conducting plates. The nanofibers aligned on top of each other perfectly in parallel lines between the two conducting plates." Innovations in engineering the simpler forms of human tissue have been arriving more rapidly of late - more scientists are involved, the tools are improving, and the cost of research is falling. This is all groundwork for the next decade and tissue engineering of complex replacement organs.

Steps towards Liver Regeneration (November 13 2008) http://www.uphs.upenn.edu/news/News_Releases/2008/11/liver-stem-cell-marker.html
Discovering a stem cell population is the first step to regenerating the tissue they support: "A novel protein marker has been found that identifies rare adult liver stem cells, whose ability to regenerate injured liver tissue has the potential for cell-replacement therapy. In the future, this marker will allow for the isolation and expansion of these stem cells, which could then be used to help patients whose livers can no longer repair their own tissue. In a healthy liver, proliferation of mature liver and bile-duct lining cells is sufficient to maintain the necessary size and function of the organ. This even works when the liver is confronted with mild and acute injury, but the situation changes when injury to the liver is chronic and severe. For chronic injury, the liver uses a back-up system that stimulates stem cells to proliferate and eventually differentiate into new liver cells. [Researchers] found that these dual-potential stem cells can be identified and potentially isolated from other liver cells."

More on Myelin Loss (November 12 2008)
http://www.eurekalert.org/pub_releases/2008-11/mnia-itw111208.php
You might recall that age-related thinning of the myelin that insulates nerves strongly correlates with declining brain function. Researchers investigating MS are making progress into the mechanisms by which this happens: the protein netrin-1 "is known to guide and direct nerve cell axons to their targets. Blocking the function of netrin-1 and one of its receptors in adult neural tissue causes the disruption of myelin. We've known for just over 10 years that netrin is essential for normal development of the nervous system, and we also knew that netrin was present in the adult brain, but we didn't know why. The new findings show that
netrin-1 and its receptor are needed to hold paranodal junctions in place, and thereby maintain the structure of myelin. The paranodal junction is a highly specialized region of contact where an oligodendrocyte cell attaches itself to the nerve cell's axon. This juncture acts as a molecular fence, which organizes and segregates the distribution of key proteins along the nerve cells axon and plays an imperative role in the proper conduction of electrical signals along the length of the nerve cell. When the function of netrin-1 and its receptor is disrupted, the organization of this adhesive junction comes apart, disrupting the function of nerve cells in the brain and spinal cord."

Brain Growth Receptors and Lifespan (November 10 2008) http://dx.doi.org/10.1371/journal.pbio.0060274
A very readable overview of recent research from PLoS Biology: "When resources are short, growing organisms face an existential choice: should you ignore the shortage and hope for better times soon, or scale back and live within your limited means? And if you do scale back, will there be any payoff later in life? For animals, these choices are played out hormonally, with environmental fluctuations leading to internal rearrangements in endocrine signal and response throughout the growing body. In mammals, two principal hormones - growth hormone (GH) and insulin-like growth factor 1 (IGF-1) - promote growth. Remarkably, inhibiting one or both of these two not only retards growth, but also extends lifespan, not just in lab animals, but possibly also in people: mutations that reduce the function of the IGF-1 receptor have recently been discovered in centenarians (who are also short). Growth occurs throughout the body, and receptors for IGF-1 are found in every organ on virtually every cell. But [researchers have now shown] that it is the IGF-1 receptors in the brain that set the pattern for growth and lifespan."

Mainstream Press on the Singularity and Longevity (November 10 2008) http://english.ohmynews.com/ArticleView/article_view.asp?menu=A11100&no=384115&rel_no=1
An interesting, if flawed, article on the singularity and engineered longevity via the Korean OhmyNews: "Amidst the rapid changes of society ranging from general advances in science and technology to politics and social policy, with respect to knowledge, there is an emergent issue that promises to radically change our lives and our reality. It is predicted that within less than 20 years, the human lifespan will be extended to perhaps 150 or more years. Scientists and futurists on the cutting edge of thought about science and society believe that the increase in lifespan is one step towards what will be known as the Singularity, at which time, life might be extended indefinitely depending upon environmental conditions. The Singularity is the term used for a technological integration unheard of; it is a theoretical future point of unprecedented technological progress, caused in part by the ability of machines to improve themselves using artificial intelligence. It was just over a hundred years ago, when the human lifespan began to double to what it is today. It is possible that most people who lived only to 35 years of age thought that to live to 72 years would be too long and that they would be too tired. Nevertheless, we have adjusted and found life to be meaningful, even in our current 'long' life of 72 years."

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."

Hub of NanoMedicine

Dear Future Centenarian,

To continue last week’s discussion of nanomedicine, here’s why you’d be interested in living long enough to see it get fully developed:
Nanotechnology refers to the control of matter on a scale normally between 1-100 nanometers. One nanometer is a billionth of a meter or 80,000 times smaller than a human hair.
We work with the world’s recognized authorities on medical applications and implications of molecular nanotechnology, or Nanomedicine. They have launched a program aimed at developing a provable nanomedical life extension technology. This may be the ultimate technology which can cure aging and reverse its effects.
They constructed a preliminary R&D roadmap and have already achieved some of their objectives. They have even established six currently active collaborations.
The technology should have commercially useful early applications. If successful, the company will eventually own a must-have product – indefinite life extension and aging reversal. In a nutshell, nanomedicine could eventually build or repair almost every cell in your body, from the bottom up, atom by atom. When we get to the 2020s, we will ultimately have perfected the machines of nanotechnology, nanobots, which are blood cell-sized devices that can go inside your body and brain to perform therapeutic functions, as well as to advance the capabilities of our bodies and brains.
If that sounds too futuristic, I'll point out that we already have blood cell-size devices that are nano-engineered, working to perform therapeutic functions in animals. For example, one scientist cured type I diabetes in rats with this type of nanoengineered device. And some of these are now approaching human trials. The 2020s will be the "golden era" of nanotechnology.
If you want to see who is at the hub of nanomedicine, visit these two websites:
http://www.MolecularAssembler.com/Nanofactory
http://www.MolecularAssembler.com/Nanofactory/Media/PressReleaseAug08.htm
Nanomedicine promises to give us complete control of matter and a very efficient way to cure aging damage, injuries and diseases. So keep fit and lean in the meantime. You don’t want to miss this boat.
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SLOW AND STEADY WINS THE RACE

Some food for thought on the way in which you approach the health basics - exercise, diet, supplementation, and relationships with physicians:

http://www.fightaging.org/archives/001582.php

"Following up on growing evidence that higher levels of conscientiousness are associated with greater health protection, the authors conducted a meta-analysis of the association between conscientiousness-related traits and longevity. Higher levels of conscientiousness were significantly and positively related to longevity. Associations were strongest for the achievement (persistent, industrious) and order (organized,
disciplined) facets of conscientiousness. Results strongly support the importance of conscientiousness-related traits to health across the life span."

The persistent application of good habits and good choices pays well. The basics are not rocket science, but they do make a significant difference over the years.
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LATEST HEALTHY LIFE EXTENSION HEADLINES

More on Comparative Longevity (October 03 2008) http://www.bucknell.edu/x45446.xml
Researchers continue to try to learn from differences in longevity and metabolism between species: "Haussmann studied cacti and turtles before zeroing in on a small, marine bird that contradicts traditional assumptions about aging. Leach's storm-petrels should die young but live a long life and break the conventional rules. First of all, they're small, and there tends to be a relationship between body size and life span. Elephants live longer than humans. Humans live longer than mice. So this bird shouldn't live long, but it does. His studies of storm-petrels have shown that certain characteristics of DNA - specifically lengths of the protective telomeres at the tips of DNA - are associated with species that live longer lives and possibly with how susceptible they are to cancer-causing tumors. [Bird species] with shorter life spans, such as zebra finches, lost their protective telomere caps quickly over time. Species such as the common tern, which lives to be about 30 years old, had less shortening over time." The petrels apparently produce more antioxidants as well - which may tie into the evidence suggesting that mitochondrial damage is the cause of shortened telomeres. Antioxidants slow the rate of that damage. The question remains as to where telomere length sits in the spectrum of cause and effect.

The Novel Paradigm of Longevity Science (October 01 2008) http://www.acceleratingfuture.com/people-blog/?p=2366
Over at Future Current, one of the presentations from Aging 2008: "What can each of us do to advance a new paradigm for health promotion and disease prevention in the 21st century that makes as its central tenet the slowing of aging? Recently, the board of directors of [the Alliance for Aging Research] committed to an aggressive effort to speak out for longevity science, which I think is a more elegant way of saying biogerontology, in order to hasten the social benefits extending healthy aging, a goal that we have referred to as 'pursuing the longevity dividend.' Now, the members of my board are not naive. They know very well that longevity science continues to be a tough sell. Let's face it, call it by any name, the quest for significantly extended lifespan has an image problem. Most established scientific leaders have been brought up to believe that aging is not only unchangeable, but not even very interesting. Now let's move to lay people. Most of them think there is not anything you can do about aging. They believe that even if you could, it would be a social and an economic catastrophe. Too many sick, old people sitting around, not pulling their weight. Even if people believed there could be some scientific breakthrough that would make it possible to extend the healthy years of life, many will set themselves up in opposition because it sounds unnatural or upsetting to social norms or religious beliefs. What will it take to overcome negative assumptions among the public?"

Life is the Road to Utopia, If You Can Stay on It (September 30 2008) http://jetpress.org/v19/bostrom.htm
From JET, a Nick Bostrom fiction in the spirit of the Fable of the Dragon Tyrant: "Your body is a deathtrap. This vital machine and mortal vehicle, unless it jams first or crashes, is sure to rust anon. You are lucky to get seven decades of mobility; eight if you be fortune's darling. That is not sufficient to get started in a serious way, much less to complete the journey. Maturity of the soul takes longer. Why, even a tree-life takes longer. Death is not one but a multitude of assassins. Do you not see them? They are coming at you from every angle. Take aim at the causes of early death - infection, violence, malnutrition, heart attack, cancer. Turn your biggest gun on aging, and fire. You must seize the biochemical processes in your body in order to vanquish, by and by, illness and senescence. In time, you will discover ways to move your mind to more durable media. Then continue to improve the system, so that the risk of death and disease continues to decline. Any death prior to the heat death of the universe is premature if your life is good. One day you or your children should have a secure home. Research, build, redouble your effort!" The road to Utopia is to continue to live well - which, as Bostrom notes, will require great labor devoted to new medical technologies of engineered longevity.

Axolotl Biochemistry as a Goal to Aim for (September 29 2008) http://pmid.us/18814845
It is plausible that mechanisms of unlimited tissue regeneration will be learned from lesser species and then ported to humans: "Urodele amphibians such as the axolotl are the champions of tissue regeneration amongst vertebrates. These animals have mastered the ability to repair and replace most of their tissues following damage or amputation even well into adulthood. In fact it seems that the ability of these organisms to regenerate perfectly is not affected by their age. In addition to being able to regenerate, these animals display a remarkable resistance to cancer. They therefore represent a unique model organism to study regeneration and cancer resistance in vertebrates. The need for this research is even more pressing at the dawn of the 21st century as we are faced with an ever aging world population which has to deal with an increase in organ failure and cancer incidence. Studying tissue regeneration in salamanders could yield significant knowledge to help regenerative medicine achieve the desired goal of allowing humans to repair and regenerate some of their own tissues as they age."

Mechanisms of Osteoarthritis (September 29 2008) http://www.eurekalert.org/pub_releases/2008-09/uorm-nsp092508.php
Researchers continue to learn more about the underlying biochemistry of common age-related conditions: "Until relatively recently, osteoarthritis was believed to be due solely to wear and tear, and an inevitable part of aging. Recent studies have revealed, however, that specific biochemical changes contribute to the disease, changes that might be reversed by precision-designed drugs. Our study provides the first solid proof that some of those changes are related to pain processing, and suggests the mechanisms behind the effect. The study revealed that pain signals originating in arthritic joints, and the biochemical processing of those signals as they reach the spinal cord, worsen and expand arthritis. In addition, researchers found that nerve pathways carrying pain signals transfer inflammation from arthritic joints to the spine and back again, causing disease at both ends. We believe this to be a vitally important process contributing to orthopaedic and neurological diseases in which inflammation is a factor."

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 Kinds 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.

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."