Longevity Meme Newsletter, August 04 2008

August 04 2008

The Longevity Meme Newsletter is a weekly e-mail containing news, opinions and happenings for people interested in healthy life extension: making use of diet, lifestyle choices, technology and proven medical advances to live healthy, longer lives.



- Three Decades From Now
- On Stem Cells and Aging
- Discussion
- Latest Healthy Life Extension Headlines


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


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

Take a look at the post above for links and more information on these topics. While you're looking through, remember that much more is needed in order to repair the damage of aging - and in most cases, that work is not yet taking place or far enough advanced for us to be confident in a good chance of it showing up in the clinic 30 years from now. We have some few years - not many, but enough if we get our act together - in which to do something about this:



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


"If many adult tissues and organs are continuously replenished by cells derived from stem cells, then why do they show signs of aging? One possibility is that stem cells themselves age and senesce, resulting in a decreased ability to replace worn-out progeny and/or the fact that they pass on aged phenotypes to their progeny. Missing in this discussion until now is the effect of the cellular and molecular environment on stem cell properties, although the molecular re-programming of epithelial cells into pluripotent stem cells demonstrates the importance of the intracellular environment. Indeed, ample evidence exists showing that intrinsic and extrinsic regulators are inextricably linked in determining stem cell functional properties. Of special current interest is the extracellular stem cell environment, commonly referred to as the stem cell 'niche', as originally coined for hematopoietic stem cells in the bone marrow."

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


The highlights and headlines from the past week follow below.

Remember - if you like this newsletter, the chances are that your friends will find it useful too. Forward it on, or post a copy to your favorite online communities. Encourage the people you know to pitch in and make a difference to the future of health and longevity!




To view commentary on the latest news headlines complete with links and references, please visit the daily news section of the Longevity Meme: http://www.longevitymeme.org/news/

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

Hourglass II Blog Carnival: Submissions Wanted (August 01 2008)
It's almost time for the second Hourglass blog carnival on the science of aging and longevity. Chris Patil of Ouroboros is looking for submissions: "The second installation of Hourglass, a blog carnival devoted to the biology of aging, will occur on August 12th. So, we're soliciting entries in the general subject area of aging and biogerontology ... Topics of posts should have something to do with the biology of aging, broadly speaking - including fundamental research in biogerontology, age-related disease, ideas about life extension technologies, your personal experience with calorie restriction, maybe even something about the sociological implications of increased longevity. Opinions expressed are not necessarily those of the management, so feel free to subvert the dominant paradigm. If in doubt, submit anyway." If you're one of the many bloggers who touch on these topics, here's a chance to see your work more widely considered.

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

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

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

Aging and Memory Formation (July 30 2008)
Researchers continue to work on our understanding of the aging brain. From EurekAlert!: "During sleep, the hippocampus, a brain region important in learning and memory, repeatedly 'replays' brain activity from recent awake experiences. This replay process is believed to be important for memory consolidation. [Researchers] found reduced replay activity during sleep in old compared to young rats, and rats with the least replay activity performed the worst in tests of spatial memory. [The researchers] recorded hippocampal activity in 11 young and 11 old rats as they navigated several mazes for food rewards. Later, when the animals were asleep, the researchers recorded their hippocampal activity again. In the young animals, the sequence of neural activity recorded while the animals navigated the mazes was repeated when they slept. However, in most of the old animals, the sequence of neural activity recorded during sleep did not reflect the sequence of brain activity recorded in the maze. ... These findings suggest that some of the memory impairment experienced during aging could involve a reduction in the automatic process of experience replay."

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

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

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

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



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