Longevity Meme Newsletter, May 07 2007

May 07 2007

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.



- A Poll on Attitudes to Death and Aging
- Exercise Your Science Muscle
- Discussion
- Latest Healthy Life Extension Headlines


Anne C. is working on a piece on attitudes towards death and aging, and is running a poll to that end; she's a quality writer, so please stop by and help out the creative process.


"Attitudes towards death and aging, and changes in those attitudes, shape the future of healthy life extension and the longevity research it depends on. If everyone was perfectly comfortable with aging to death (and the inevitable frailty, helplessness, pain and suffering), then it seems self-evident that there would be little or no funding for meaningful anti-aging science. If everyone desired health and longevity, and acted rationally on that desire, then the aging research community would be afloat upon a sea of banknotes."

Reality is somewhat more complex and labored, of course. Convincing a multitude of people to help produce healthy life extension for all is most likely going to be more of an endeavor than the process of developing working longevity medicine when popular opinion, and the resources that come with it, are on our side:



I'm of the opinion that it is as helpful to understand something about mitochondria, telomeres and cellular processes - and to keep up with the major new changes in scientific consensus - as it is to know, basically, why exercise is good for you. How else are you going to measure the legitimacy of the next story in the popular science press, or effectively manage the next few decades of health choices through this rapidly accelerating biotechnology revolution?


"We know that mitochondrial damage is tied to aging via mechanisms such as the production of damaging free radicals such as ROS - and that some researchers are working on solutions, such as the ability to replace all mitochondrial DNA in the body via protofection. We also know that progressive telomere shortening is tied to aging and age-related disease, and a number of different groups are working on strategies to safely lengthen telomeres. ... This paper offers the possibility that if we repair or prevent the progressive accumulation of mitochondrial degeneration and damage, then the telomeres will take care of themselves - if the results are replicated, of course."


"Autophagy is, broadly speaking, the process by which your cells recycle damaged components. Cells are packed full of building blocks dedicated to specific tasks, and few of them are designed to last. The average cell is a little powerhouse of dynamic destruction and construction ... more autophagy appears to be a good thing. You don't want damaged organelles running wild in your cells; one only has to look at the mitochondrial free radical theory of aging to see where that can lead - a trick of biochemistry prevents mitochondria from being recycled, and ever more damaged cells spew toxins into your body, causing the degenerations of aging that follow."


"Do you want damaged stem cells churning away, raising the risk of the biochemical accidents that generate cancer, or do you want to damp down the repair function, thereby accumulating more damage that causes aging? No good choice there, but the future of medical science provides other approaches - such as repairing the damage via new technologies."


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!


Founder, Longevity Meme



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/

More on Cellular Micromachines (May 06 2007)
Via the Cantonsville Times, another look at the near future of medical devices - make them small, make an army of them, and build them exactly like cells: "Imagine not having to go to the doctor when you are sick. No medicine, no popping pills. Instead, tiny cell-like machines in your body would manufacture medicine and deliver it exactly where it is needed. University of Maryland researchers said these 'nanofactories' may not be that far away. Nanofactories are pseudo-cells that are swallowed, inhaled or absorbed through the skin and travel to a specific location in the body. What's unique about these tiny biochemical factories is that they could potentially use materials already in the body to manufacture medicine at the first sign of infection or disease. ... You actually take components and make something that wasn't there before. It takes things from their environment and puts them through the factory and generates something important." Our cells are tiny, complex machines - varied, efficient, autonomous robots in effect. Since we want more of the same, but tailored to our design, why not start with the blueprint that's right under our noses?

The Fading Ability to Heal (May 06 2007)
(From ScienceDaily). Diabetes is often used as a model for aging by researchers, as some of the underlying mechanisms or consequences are similar. Here, researches examine the mechanisms by which healing works, and then ceases to work with disease progression. " Endothelial progenitor cells (EPCs), which derive from bone marrow, normally travel to sites of injury and are essential for the formation of blood vessels and wound healing. ... The authors examined diabetic mice and found that increased oxygen levels (hyperoxia) enhanced the mobilization of EPCs from the bone marrow to the peripheral blood circulation. The high oxygen levels increased the activation of the bone marrow enzyme eNOS, which stimulated nitric oxide production, helping to produce greater numbers of EPCs. However, local injection of the chemokine stromal cell-derived factor 1 alpha (SDF-1alpha) was required to recruit these EPCs from the circulation to the wound site. The increased presence of EPCs at the wound site resulted in accelerated wound healing. The authors concluded that impaired eNOS activation and decreased SDF-1alpha expression in diabetes are responsible for the defect in diabetic wound healing." Failures in this healing process exist in aging due to the accumulation of damage in vital components of our biochemistry. We should hurry to repair that damage just as we hurry to cure diabetes.

A Look Inside the CALERIE Study (May 05 2007)
From the Daily Reveille: "Pennington Biomedical Research Center conducts what Assistant Communications Director Alan Pesch called an 'exciting' two-year study on the effects of calorie restriction. The new study, CALERIE II, marks the second phase of a $12.4 million, seven-year study launched in 2002. ... Pennington researchers and others have already successfully linked caloric restriction to longevity in small animals and organisms. ... We know it's been working for flies, worms, yeast and then mammals like rats and mice. All the data are consistent, and the question is: Do we have any evidence that it can work in humans? ... Pennington will use a variety of techniques to analyze test subjects' metabolism, which may affect longevity. Researchers will also examine genes they believe may control bodily responses to caloric restriction. Though the study examines the effects of caloric restriction, Pennington plans to test whether subjects can realize a longer life through increasing activity levels. ... There is something we don't understand totally that keeps your cells in the body younger ... Pennington will accept 100 qualified men and women for the upcoming two-year study. Enrollment begins in late summer."

An Interview With Guarente And Butler (May 05 2007)
Via the transhumantech list, an interview with researcher Lenny Guarente and Robert Butler of the International Longevity Center, folk from the longevity dividend camp: "I dont think of life span as the gold standard. The gold standard is health span. All the indicators from the laboratory are that the genes were studying and the kinds of drugs we would be developing would extend health span. If you can extend health span, and you also happen to extend life span, so be it. Thats a side benefit. ... Why does 50 percent of all cancer occur after 65? Why does 80 percent occur after age 50? As we age, there are changes at the cellular molecular level that predispose us to disease and disability. But so far, no government, no foundation, no corporation anywhere in the world has fully embraced the importance of longevity science. If we could target aging, that would have an impact on diseases." He means no foundation of massive size of course - the Methuselah Foundation is way ahead of the longevity dividend position. It is interesting to note that Guarente puts a timeline of 10-15 years on the arrival of drugs to replicate the effects of calorie restriction on healthy longevity.

Nuts and Bolts of Naked Mole-Rat Longevity (May 04 2007)
While we're on the subject of oxidative stress, here's a paper looking at just how resistant naked mole-rats are to oxidative damage. This seems to be the root of their eight-fold longevity over similarly sized rodent species. "The naked mole-rat (NMR; Heterocephalus glaber) is the longest-living rodent known (maximum lifespan potential [MLSP]: >28 years) and a unique model of successful aging showing attenuated declines in most physiological function. This study addresses age-related changes in endothelial function and production of reactive oxygen species in NMR arteries and vessels of shorter-living [rats]. ... long-living NMRs can maintain a youthful vascular function and cellular oxidant/antioxidant phenotype relatively longer and are better protected against aging-induced oxidative stress than shorter-living rats." The short version of the story is that - by a whole range of biochemical measures - naked mole-rats just don't show much evidence of this aspect of degenerative aging, an aspect that causes great suffering for we humans. As for several other species of mammal, the mole-rats indicate there is great room for improvement in the human model. Which is interesting, but certainly not the fast path to greatly extended lives, for all that we live in the midst of a revolution in biotechnology - it's much easier to learn to fix damage in the present model than to rework our biochemistry to resist that damage.

CR Makes For Efficient Mitochondria (May 04 2007)
Via PLoS Medicine, a look at the benefits calorie restriction (CR) brings to mitochondrial function - and hence to your long-term health: "A calorie-restricted diet provides all the nutrients necessary for a healthy life but minimizes the energy (calories) supplied in the diet. ... A major factor in the age-related decline of bodily functions is the accumulation of 'oxidative damage' in the body's proteins, fats, and DNA. Oxidants - in particular, chemicals called 'free radicals' - are produced when food is converted to energy by cellular structures called mitochondria. One theory for how caloric restriction slows aging is that it lowers free-radical production by inducing the formation of efficient mitochondria. ... The induction of these efficient mitochondria in turn reduces oxidative damage in skeletal muscles. Consequently, this adaptive response to caloric restriction might have the potential to slow aging and increase longevity in humans as in other animals. ... CR and CR [plus exercise] both increased the number of mitochondria in skeletal muscle. Both interventions also reduced the amount of DNA damage - a marker of oxidative stress - in the participants' muscles." The normal caveats are given, but the more we learn about the mechanical operation of calorie restriction, the better it looks, given that it costs nothing but thought and time to try.

"Ending Aging" At Amazon (May 03 2007)
The Methuselah Foundation notes that the forthcoming SENS book is now available for pre-order at Amazon: "Which means we all now know the title: Ending Aging: The Rejuvenation Biotechnologies That Could Reverse Human Aging in Our Lifetime. Having edited drafts earlier this year, I'm in a position to say: buy it. 'Ending Aging' provides a far richer introduction and overview of SENS science, of the real prospects for progress in extending our healthy life spans, and of the nuts and bolts of getting there, than any other material published to date. If you are in the demographic who finds the information at the SENS website too little, but the interlinked world of scientific papers on longevity science too much, and have A Brief History of Time in your collection, then this book is for you." Ending Aging arrives in September, and is well worth the wait. Michael Rae, Aubrey de Grey and the Foundation volunteers have done a superb job.

Manipulating NAD For Longevity (May 03 2007)
Scientists continue to try and recreate aspects of the biochemical changes brought on by calorie restriction, in an effort to generate the health and longevity benefits via medicine. An example can be found at ScienceDaily: "a newly discovered vitamin activates the yeast anti-aging gene product Sir2, which resembles sirtuins found in humans. ... NR (nicotinamide riboside), a natural product found in milk. Like the B3 vitamin, niacin, NR is a precursor to a versatile cellular factor that is vital for all life. The factor, called NAD, short for nicotinamide adenine dinucleotide, is elevated by calorie restriction. So the researchers set out to develop an intervention to elevate NAD, using yeast cells, whose genes are easy to manipulate. ... It's surprising that no one was be able to elevate NAD with a small molecule before ... The team discovered two pathways that allow yeast to raise NAD levels with NR, improve their control of gene expression and live longer in the presence of high glucose." Some folk in the gerontology community are skeptical, pointing out that no success has been obtained in mammals through the use of other precursor biochemicals in this pathway - this may be one of the many differences rather than similarities between yeast and people.

More On PHA-4, Calorie Restriction and Longevity (May 02 2007)
A better article on the latest calorie restriction gene via EurekAlert!: "After 72 years of not knowing how calorie restriction works, we finally have genetic evidence to unravel the underlying molecular program required for increased longevity in response to calorie restriction ... Loss of only one of the genes, a gene encoding the protein PHA-4, negated the lifespan-enhancing effect of calorie restriction in worms. And, when researchers undertook the opposite experiment - by overexpressing pha-4 in worms - the longevity effect was enhanced. ... So far, only one other gene, called sir-2, has been implicated in the life- and health-prolonging response to calorie restriction. Increased amounts of SIR-2 protein extend longevity of yeast, worms, and flies, but while loss of sir-2 disrupts the calorie restriction response only in yeast, it has no effect on other organisms, such as worms. ... We know three distinct pathways that affect longevity: insulin/IGF signaling, calorie restriction, and the mitochondrial electron transport chain pathway, yet it is still not clear where sir-2 fits in. It seems to meddle with more than one pathway. PHA-4 is specific for calorie restriction as it does not affect the other pathways."

Towards a Progeria Therapy (May 02 2007)
From Newswise, an update on progress towards treating progeria - and maybe "normal" aging too: "Scientists studying the genes of two infants who died of mysterious illnesses found the infants had mutations in LMNA, the same gene altered in patients with the premature aging condition progeria. ... when researchers treated cell samples from one of the patients with a drug targeted for progeria, they saw signs that the cells were improving. ... progeria treatment may not be as distant as we thought. If physicians can reduce production of bad lamin A by as little as half in progeria patients, we might see significant improvement. ... Progeria treatment also has potential implications for larger populations. The LMNA gene is involved in several other more prevalent disorders including forms of muscular dystrophy and heart disease. ... recent studies by other labs have shown that occasional errors in the production of lamin A may take place even in people with 'normal' copies of the gene. Scientists suspect that accumulation of these bad copies may contribute to aging. If so, treatments that work for progeria patients may one day be adapted to reduce the effects of aging."

A New Calorie Restriction Gene (May 01 2007)
The Wall Street Journal reports on another gene that regulates the benefits to health and longevity produced by calorie restriction: "This gene is absolutely essential for the response to dietary restriction [in] prolonging life span ... we're still in the identification [of genes] phase and a long way from clinical trials. ... The gene [known] as PHA-4 was discovered in worms, where it plays a key role in the embryonic development of the intestine. However, PHA-4 also coordinates other genes that influence how the adult worm's body responds to a restricted diet. Humans possess three genes that are very similar to PHA-4. ... The gene is highly conserved in humans, mice and worms. So its function in humans could be similar. ... Other researchers have studied a different gene, SIR-2, which plays a role in extending longevity of yeast, worms and flies. However, its role isn't as specific in influencing the calorie-restriction response as PHA-4." So continues the process of narrowing down the focus: how exactly is it that calorie restriction extends healthy life? When that question is answered, engineering similar benefits for everyone through medical science becomes a plausible goal - albeit not as efficient a way forward as other plausible goals.

We Should View Aging As Curable (May 01 2007)
Randall Parker lends his voice to common sense foresight for medicine and longevity: "I would [argue] that the general advance in biotechnology, with the continuing development of much more powerful tools to measure and manipulate biological systems at the molecular level, makes the idea of rejuvenation seem much more attainable. ... [we should] expect orders of magnitude more powerful tools in a couple of decades. Just as the shrinking size [of] computer technology allows computer chips, hard drives, fiber optics, and transceivers to go through long series of doublings in capability so does the miniaturized level at which biological instrumentation advances. Why shouldn't we treat aging as curable? The amazing physicist Richard Feynman gave a speech in 1959 entitled There is plenty of room at the bottom where he argued that we can develop the ability to manipulate matter at the molecular level. A continuing trend in technology since that speech has been the development of tools to better measure and manipulate increasingly smaller amounts of material. ... That trend is also going to lead to technology that allows us to make nanodevices that can repair human tissue at the level of individual cells and molecules."

Intestinal Bacteria and Ageing (April 30 2007)
In light of recent research into the effects of calorie restriction on those little plants and animals that live in your gut, this would seem interesting: "The intestinal microbiota is important for maintenance of host health, providing energy, nutrients and protection against invading organisms. Although the colonic microbiota is relatively stable throughout adult life, age-related changes in the gastrointestinal (GI) tract, as well as changes in diet and host immune system reactivity, inevitably affect population composition. Recent studies indicate shifts in the composition of the intestinal microbiota, which may lead to detrimental effects for the elderly host ... These changes, along with a general reduction in species diversity in most bacterial groups, and changes to diet and digestive physiology such as intestinal transit time, may result in increased putrefaction in the colon and a greater susceptibility to disease. Therapeutic strategies to counteract these changes have been suggested in ageing people." Will this turn out to have as much of an effect on healthy longevity as, say, exercise or calorie restriction? Possibly, you never know. Invariably, these line items pale before the future of longevity science, however - stay focused on the big picture.

How Autologous Stem Cell Therapies Work (April 30 2007)
How is it that autologous stem cell therapies work? From ScienceDaily: new work is "shedding light on the previously mysterious mechanism through which even relatively small amounts of stem/progenitor cells taken from a patient's own bone marrow enhance repair of damaged tissues. ... The cells not only differentiate to replace injured cells, as had been understood, but they also stimulate the proliferation and differentiation of stem cells already present in the injured tissue and they transfer mitochondrial DNA to local cells in which the mitochondria (the energy of the cell) is not working. Better understanding of the different mechanisms of these stem/progenitor cells suggests multiple strategies for developing new therapies for a broad range of diseases. ... the studies are explaining the mechanisms by which the cells work, in animals and in the more than 1,000 cardiovascular and other patients in the United States believed to be enrolled in clinical trials using these cells taken from their bone marrow." The mitochondrial transfer is certainly interesting. Could we make inroads in repairing age-damaged mitochondria via the application of stem cells in addition to the more obvious methods?



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