Longevity Meme Newsletter, May 05 2008

May 05 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.



- Your Future Bioartificial Immune System
- An Interview With Peter Thiel
- On the "Anti-Aging" Marketplace
- Discussion
- Latest Healthy Life Extension Headlines


Technology demonstrations in immunotherapy and control of cells today form the groundwork for the bioartificial immune systems of the late 2020s:


"Producing immune cells, directing their actions, deciphering the biochemistry of pathogens - all these pieces are waiting to be put together as a bioartificial immune system, many times more selective, efficient and resistant to damage than the basic version we're all equipped with. For added effect, it will also slay cancer cells and degrade the buildup of dangerous compounds, such as the amyloid beta associated with Alzheimer's disease."

Once you've demonstrated the capabilities in isolation - and all the above items have been demonstrated in the laboratory, or are presently in clinical trials - you can easily imagine the integrated product of the future; cells and biological cell-like micromachines working in concert, programmed and updated by medical technicians. Many of the most effective medical tools of the 2020s are probably going to look a lot like a collection of programmable cells:



For those of you interested in the thinking behind investor Peter Thiel's multi-million dollar support of longevity research at the Methuselah Foundation:


"There is a category of things that would benefit all of humanity but where the benefits are very diffuse and the costs are concentrated. Maybe it's very long-term. So I focused my philanthropy on things with a 20-, 30-, 40-year horizon. The horizons are too long for a for-profit company to take advantage of, and the government and universities are not pushing things because maybe it's too unconventional or it doesn't easily fit into a particular political agenda or vision of the future. Those areas are probably systematically underfunded. It may be the only area of philanthropy that's underfunded."


Some thoughts and dissents on what the vast "anti-aging" industry and its nostrums mean to scientific efforts aimed at actually repairing and reversing the damage of aging:


"As I've pointed out in the past, the massive "anti-aging" marketplace sometimes looks as though it could provide great benefits to the healthy life extension community - a group of enthusiastic people and their delivery and marketing networks, flush with money, just lacking any product that actually works. But in practice, it just doesn't work out that way. Merchants focused on making money from things that don't work will keep doing just that and no more. The people buying the products show little to no sign of crossover to support of real longevity science.

"Did Florey team up with the county fair salesman to market penicillin? ...Of course not. So why ought the anti-progress attitude of the cosmetics frauds have any bearing on those pursuing the real deal?"


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/

Calorie Restriction and Dietary AGEs (May 02 2008)
It looks plausible that some portion of the health and longevity benefits of calorie restriction stem from a reduction in the intake of dietary advanced glycation end products (AGEs). AGEs are created in the body as a metabolic side-effect, but also found in your food: "Increased oxidative stress (OS) underlies many chronic diseases prevalent in aging. Data in humans confirm the hypothesis that [AGEs] and other oxidants derived from the diet may be major contributors to increased OS in normal adults as well as those with diabetes mellitus or kidney failure. Mice fed a diet with a lowered (approximately 50%) content of AGEs or a typical calorie-restricted (CR) diet, accumulated a smaller amount of AGEs [and] did not have increased oxidant stress or cardiac or kidney fibrosis with aging. However, the findings in mice fed a CR diet with an increased content of AGEs resembled those in mice fed a nonrestricted diet that had the usual higher content of AGEs. Thus, there was an inverse correlation between the dietary AGE content, [oxidative stress], organ damage, and life span."

More Stem Cells Than Thought, Perhaps (May 02 2008)
Ouroboros on just how many stem cells we have: "It is widely accepted that stem cells are involved in tissue regeneration. It is also widely accepted that (in most organs) stem cells are vanishingly rare. So: if there doesn't happen to be a stem cell adjacent to a site of damage, how can stem cells be involved in the process of tissue repair? There might be more stem cells than we think, because we've been missing them for some reason. This possibility is strongly supported by the recent findings of Zuba-Surma et al., who have discovered a population of tiny pluripotent cells (termed, appropriately, very small embryonic-like, or VSELs) scattered throughout the body. ... Note that both VSEL number and potency diminish with age, consistent with the decrease in proliferative and regenerative capacity that we see in older animals. ... Required skepticism: VSELs are both brand new and (so far as I can tell) idiosyncratic to a single group's work. Before we get too worked up about this, I'd like to see the work reproduced by other labs and in other systems. Hopefully that sort of confirmation is already underway." The easier stem cells become to source, the faster research and development will proceed.

Targeted Chelation Versus Lipofuscin Buildup? (May 01 2008)
In a similar fashion to the way in which antioxidants change from dubious to demonstrably beneficial for lifespan when targeted to mitochondria, it is proposed that chelation targeted to the cell's lysosomes can slow the accumulation of lipofuscin in your cells. You might recall that lipofuscin buildup with age contributes to age-related degeneration by eventually destroying the ability of cells to function. "Since the sensitivity of lysosomes to oxidative stress can be manipulated by altering the intralysosomal level of redox-active iron, it follows that lipofuscin formation might also be influenced. It is suggested that pulse doses of iron chelators that easily penetrate membranes could be used to diminish lipofuscinogenesis." But don't run out to buy chelation products - ingesting that stuff won't send it anywhere near your lysosomes, just as swallowing antioxidant products won't affect your mitochondria. More engineering is needed, and in this case a technology demonstration to confirm the proposal.

Stress and the Damage of Aging (May 01 2008)
Stress speeds some modes of age-related decline, probably via the mechanisms of chronic inflammation: "Responses to stress anticipate adaptation to an unacceptable disparity between real or imagined personal experience and expectation, including adaptive stress, anxiety, and depression. However, if stress persists, it may lead to chronic diseases, ranging from inflammation and cancer to degenerative diseases. For some time, only remarkable stress was acknowledged to induce immune and vascular alterations, such as infection or hypertension. Now it is known that moderate stress independent of conventional risk factors can induce a potent alteration of health conditions and consequently shorten life quality and lifespan. ... Stressful life conditions turn out to induce a diffuse (systemic) pro-inflammatory status. Subclinical chronic inflammation is an important pathogenic factor in the development of metabolic syndrome, a cluster of common pathologies, including cardiovascular disease." As for other lifestyles that induce chronic inflammation, you can wait (and suffer) while researchers build drugs that block the mechanisms at fault, or you work to change your circumstances to cause less damage over the long run.

Plan For a Longer Life (April 30 2008)
Life expectancy is increasing, and the rate of increase is accelerating. People live longer than they expect to live. If you lay the foundations of your future - savings, investment, work - with an eye to your grandparent's lifespan and strategies, then you're not planning well. "As greater longevity is increasingly becoming a fact of life, people are leaving themselves vulnerable to financial hardship at a time when they are most in need ... Nearly half the population of the UK said they were only expecting to live to the same age as their parents' generation ... Interestingly, whilst people do not realise the possibility of themselves living longer than their parents, they do recognise that their children will live longer lives than they will. However, 18-24 year olds grossly underestimate this, with only 25% of them thinking that their children will live longer, whilst 44% 55 year olds thought this. ... People acknowledge increased longevity for younger generations but do not realise that this is a very real issue for them today." Plan for an interesting future - and recognize that you have more than enough time to save and invest all you will need, even in the best scenarios of radical life extension.

Deadlines For the Understanding Aging Conference (April 30 2008)
The Understanding Aging conference will be held in Los Angeles in late June, and the early registration and abstract submission deadlines are only two weeks away. By mail from conference organizer Aubrey de Grey: "The program has over two dozen confirmed speakers, all of them world leaders in their field. As for previous conferences I have [co-] organised, the emphasis of this meeting is on 'applied biogerontology' -- the design and implementation of biomedical interventions that may, jointly, constitute a comprehensive panel of rejuvenation therapies, sufficient to restore middle-aged or older laboratory animals (and, in due course, humans) to a youthful degree of physiological robustness. ... registration for the conference includes preferential admission to the free public preconference 'Aging: the disease, the cure, the implications.'" You'll recognize many of the names on the conference agenda - an assembly of leaders in their fields and people of influence.

Metabolic Rate, Mitochondria and Mammalian Lifespan (April 29 2008)
Correlations are pointers - they indicate where future research and development may best be directed. Here, researchers demonstrate a strong correlation between mammalian life span and various mitochondrial characteristics: "In animal cells, mitochondria are semiautonomous organelles [with] their own code and genome (mtDNA). The semiautonomy and restricted resources could result in occasional 'conflicts of interests' with other cellular components, in which mitochondria have greater chances to be 'the weakest link,' thus limiting longevity. ... (1) to what extent the mammalian maximum life span (MLS) is associated with mtDNA base composition? (2) Does mtDNA base composition correlate with another important mitochondria-associated variable - resting metabolic rate (RMR) - and whether they complement each other in determination of MLS? ... Analysis of 140 mammalian species revealed significant correlations ... To the authors' knowledge, it is the highest coefficient of MLS determination that has ever been reported for a comparable sample size. Taking into account substantial errors in estimation of MLS and RMR, it could mean that [this explains] most of the MLS biological variation. [This leads us to] mitochondria as a primary object for longevity-promoting interventions."

The Next Step For Engineered Pluripotency (April 29 2008)
This paper proposes that the next step for recent advances in engineering pluripotent stem cells is to create these cells directly, inside the body: "Stem cells are the major factor ensuring mammalian regeneration. Cell replacement therapy is an attempt to follow this natural process. Another strategy suggests a controlled de-differentiation of somatic cells to a stem-like state with subsequent re-differentiation. Indeed, the cultured mammalian somatic cells may be reprogrammed to a pluripotent state by the induction of a specific set of genes. The next logical step toward the goal of organism rejuvenation is to test the possibility of inducing the pluripotent state in somatic cells in vivo. Such an approach has the potential to improve upon and overcome several obstacles facing today's cell replacement therapy." This is an interesting line of thinking; why not simply create new stem cells right where they are needed?

The Power of Targeting (April 28 2008)
If you've been following along, you'll recall that many of the most interesting biotechnology demonstrations in recent years work because they target very specific parts of the cell. For example, targeting antioxidants to the mitochondria extends life in mice where straightforward application of antioxidants does not. Here, the Telegraph reports on a related approach for an Alzheimer's therapy: hitting a part of the disease mechanism that's already been tried, but this time localizing the action of the drug to a specific structure within the cell. "The drug targets the membrane of brain cells, focusing on compartments in the membrane, called 'rafts', that play a central role in many cellular processes. Although this drug is not the first to target the enzyme, called beta secretase, it is the first to do so in the right place, in the 'intracellular membrane compartment' where the enzyme triggers the protein deposit build-ups. The team has devised a way to anchor the drug to the membrane to stop the harmful deposits."

The Terrible Cost of FDA Regulation (April 28 2008)
ShrinkWrapped expands on the terrible cost imposed upon progress by the FDA: "The development of our cumbersome and onerous regulatory environment that will slow the availability of drugs to those who would benefit from it is a sad story of missed opportunities and risk aversion ... the FDA was established and set up a framework for approving drugs only after they were shown to be safe and effective. The terrible problem for medicine is that there is no such thing as a drug that can be proven to be completely safe. ... On every level it makes sense for us to develop anti-aging treatments. Losing the abilities of those who are most skilled and experienced on a regular basis is wasteful of human resources. Yet our current regulatory environment not only precludes developing drugs that could slow aging, but makes studies to show their safety and effectiveness impossible to perform. ... as in any bureaucracy, the FDA is not going to be able to modify its mandate without a tremendous push from those most likely to be effected by their conservatism."



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