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."