Longevity Meme Newsletter, January 21 2008

January 21 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.



- Revisiting Longevity Insurance
- DNA Damage and Targeting Mitochondria
- A Thought For the Day on Aging
- Discussion
- Latest Healthy Life Extension Headlines


A large portion of the insurance industry will be betting against accelerating longevity in the years ahead, despite all the signs that the rate of increase in healthy life span will only increase. We are, after all, in the early stages of nothing less than a revolution in biotechnology and medicine. This won't end well for investors and policy holders when insurance companies go under - and quite possibly for all the rest of us as well, given the way that politicians try to pass along the cost of bad business decisions made by the well-connected few. The consequences of betting against longevity have been illustrated in the past:


"Tontines were the first government bonds issued anywhere in the world, and the British government first issued tontines in 1693 to fund a war against France. However, tontines soon caused problems for their issuing governments, as they would increasingly underestimate the longevity of the population."

Those who fail to learn from history are doomed to repeat it.


A look at the state of a few strands of the science of aging:


"Does the accumulation of DNA damage in the cellular nucleus contribute to significantly to aging? How, if so? It is a topic for debate, with a weight of papers behind many of the consensus interpretations, but most of the community would answer 'yes' with some variety of qualifications. ... it isn't hard to find academic arguments for the role of DNA damage in most of the better known age-related degenerations. It's a matter of time, resources for research and scientific debate as to which pan out."

It is accepted that cancer is a consequence of DNA damage, but the relationships of other aspects of degenerative aging to accumulated mutations in our nuclear DNA are much argued. Is declining stem cell capacity with age caused in part by DNA damage, for example? A good question - and one that has yet to be answered in any firm manner.

Let's move on to your other DNA, contained in mitochondria, the power plants of your cells. Originally symbiotic bacteria, and now a vital cellular component, mitochondria have retained the functional portions of the ancient DNA they brought to the party. The weight of evidence for a connection between damaged mitochondrial DNA and aging is much greater than for nuclear DNA, and researchers are far closer to being able to do something about it:


"Your mitochondria are a source of a whole lot of biochemical trouble as the years go by. Damaged mitochondria proliferate in some cells and, like damaged factories, pollute the cells with excess reactive oxygen species and free radicals produced as metabolic byproducts. Each damaged cell then tries to maintain itself by exporting more reactive oxygen species and free radicals from its cell membrane structures, spreading the damaging pollution far and wide in the body. ... Repairing or replacing damaged mitochondria is one way to strike at the root of this process, and a number of groups are working on that ... The SENS research program identifies a different and even more fundamental way forward: create a backup in the cell nucleus for specific mitochondrial processes that cause all these problems when damaged."

"Another approach that's out there in the field is to target antioxidant chemicals to the mitochondria, where they can be effective in soaking up some fraction of the excess free radicals before they wreck havoc. Antioxidants in general don't seem to be terribly effective when simply thrown at our biochemistry. While making a difference, targeted antioxidants are clearly only a delaying tactic - as opposed to repair strategies that can be performed indefinitely ... This is what medicine looks like at the base layer these days - a lot of organic chemistry, building molecules that tweak other molecular machinery in a particular way. Manipulating mitochondria to reduce their contribution to aging and age-related disease is a growth field; you'll be seeing a lot more of it in the years ahead."


Some thoughts on aging and attitudes toward aging:


"Brain aging is gradual brain damage. Some people think aging is wonderful and natural. That's tantamount to saying that brain damage is wonderful and natural."

Most people have been brought up in - and actively maintain - what Aubrey de Grey calls "the pro-aging trance." This is far greater a hurdle to progress in longevity and rejuvenation medicine than the research challenges that lie ahead. Many supporters and great application of resources will be required to take full advantage of the potential for enhanced longevity inherent in the biotechnology revolution. That can only happen if many people first understand that far longer lives are possible, and secondly want that to happen earnestly enough that they are willing to get up and do something about it.


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/

Aging and Genomic Instability (January 18 2008)
Ouroboros looks at recent longevity research in the context of DNA damage and other genomic instability - a good follow-on to a recent post on that subject at Fight Aging!: "Earlier this week we learned that mutations in the kinase SCH9, combined with intervention in the RAS and TOR pathways, can extend the chronological lifespan of yeast by as much as tenfold. ... Mutation of SCH9, which extends lifespan on its own, suppresses the longevity-shortening phenotype of SGS1 deletion. Since calorie restriction (CR) has no effect on chromosomal rearrangements in the SGS1 mutants, this study has parsed the contributions of SCH9 and CR to at least one molecular correlate of aging (specifically, genome stability). The authors argue that their results further demonstrate the importance of genome stability to the aging process, a point on which certain researchers focusing on mammalian aging would agree. The question remains, however: Does genomic instability shorten lifespan by increasing transcriptional noise, as suggested by the Vijg lab's stochasticity experiments, or via another mechanism?" A good question indeed. The precise relationship between damage to the genome and aging is up for debate.

More Stem Cells Versus Parkinson's (January 18 2008)
A number of groups are working to engineer replacement neurons for those gradually destroyed by Parkinson's disease. Here's another, noted at EurekAlert!: the "team studied the development of [dopaminergic] neurons in animals to determine the important biological molecules in the brain that were necessary for the cells to grow and function efficiently. The scientists identified one particular molecule that seemed to be key, a protein called Wnt5a. They showed that when this molecule, together with a second protein called noggin, was included in cultures of stem cells, far more [dopaminergic] neurons were produced than when these ingredients were not present. ... they used neural stem cells - which are programmed to develop only into nerve cells. ... When the researchers transplanted the cells into laboratory animals whose substantia nigra region of the brain was damaged, the results were promising. ... We reversed almost completely the behavioural abnormalities, and neurons differentiated, survived and re-innervated the relevant part of the brain better. Furthermore we do not see the kind of proliferation of the cells that has occurred in the past and we get very little clustering."

More Potential Keys to Cancer (January 17 2008)
ScienceDaily brings news of more potentially common biomechanisms of cancer: "The gene, USP22, encodes an enzyme that appears to be crucial for controlling large scale changes in gene expression, one of the hallmarks of cancer cells. ... USP22 was part of a group of 11 genes that are overexpressed in a variety of cancers and that overexpression of USP22 predicts which tumors can go on to spread elsewhere in the body. This group of genes is collectively called the 'cancer stem cell signature.' ... Since USP22 is an enzyme, the type of protein that is easiest to target with drugs, our new findings may help extend these earlier discoveries to the point where therapeutics can be developed. There are already drugs being used in cancer patients that attack other enzymes in this pathway, and there are companies interested in extending this to find USP22 inhibitors." If it turns out that less than 20 key mechanisms can be used to shut down 80% of cancers, few of you reading this today will ever suffer from cancer. That is one of the many promises of the biotechnology revolution: knowledge is power.

Andy Grove and Parkinson's Research (January 17 2008)
A profile of Andy Grove and his initiatives and views can be found at Forbes: "before [Parkinson's disease] debilitates him, Grove is going to fight. Over the past eight years Grove has immersed himself in the minutiae of the disease and has used his money and his stature to agitate for more and faster research on the neurology of Parkinson's. ... You can't go close to this and not get angry. There are so many people working so hard and achieving so little. ... Grove criticized research funding at the U.S. National Institutes of Health, the unwillingness of researchers to share data and the lack of urgency in translating basic science into treatments that can help people. ... What is needed is a cultural revolution that values curiosity, follow-through and a problem-solving orientation and also puts the data being generated in full view, scrutinizable by all." This is the same story for all us - just change Parkinson's to aging and add a couple more decades before the clock ticks down. We're in exactly the same position otherwise, and the mainstream research community is just as disinterested in progress and goal-setting.

Repairing Macular Degeneration (January 16 2008)
Progress in biological engineering via the Telegraph, this time in repair strategies for the macula: "More than 500,000 people in the UK have irreversible blindness caused by macular degeneration ... The disease is marked by a progressive loss of central vision due to degeneration of the macula - a pigmented spot at the back of the retina. ... Using surgical instruments introduced through three one millimetre holes in the eye, the team goes under the retina, a translucent layer, then inflate it so it separates from the underlying cells. The human eye cells derived from embryonic cells were then introduced on a rolled up patch and injected through a one millimetre hole, where the patch of human cells unfolded under the retina. ... The results are really encouraging. We plan to do the first patient within three years ... As a human trial run for the operations, the team has also repaired the vision of four out of 12 patients with the wet form of macular degeneration by moving around their own tissue within the eye." A decade from now, this sort of early regenerative medicine will be commonplace and widely available.

Targeting Cancer Stem Cells (January 16 2008)
The Telegraph looks at a representative initiative aimed at the targeted elimination of cancer stem cells: researchers "have found a strategy that selectively targets these cancer stem cells for destruction, successfully halting the spread of one of the deadliest cancers - melanoma - in mice. ... Not every cell in a cancer are the same. There is a population of cancer stem cells. But it has never been shown that targeting them can halt tumour growth. This is a very important study when it comes to validating this approach for future treatments ... The team took mice that were growing human tumour cells from melanoma patients, then injected the rodents with monoclonal antibodies - proteins designed only to bind with the ABCB5 protein and thus the melanoma stem cells. They found that this stimulated an immune response that killed tumour cells and significantly inhibited melanoma growth as compared with untreated mice. ... It is of course preliminary and it would be wrong to raise false hopes but many are trying to turn cancer stem cell targetting into therapy."

Calorie Restriction Versus Sarcopenia (January 15 2008)
An interesting review paper connecting a few previously published links in the chain: "Aging is inevitably associated with a progressive loss of muscle mass and strength, a condition also known as sarcopenia of aging. Although the precise mechanisms underlying this syndrome have not been completely elucidated, recent studies point toward several key cellular mechanisms that could contribute to age-associated muscle loss. Among these, mitochondrial dysfunction and deregulation of apoptotic signaling have emerged as critical players in the onset and progression of sarcopenia. Interestingly, calorie restriction, a well-known antiaging intervention, and, more recently, exercise training have been shown to beneficially affect both mitochondrial function and apoptotic signaling in skeletal muscle from young and old animals. Preliminary observations also indicate that even a small (8%) reduction in food intake may still provide protective effects against sarcopenia and cellular remodeling in aging skeletal muscle, with the advantage of being more applicable to human subjects than the traditional 30-40% restriction regimen." This is the era of understanding - at the deepest level - why good health practices extend healthy longevity.

Constructive Thoughts on Raising Awareness (January 15 2008)
As we continue to raise awareness and support for healthy life extension science, it is important to expand the public dialog. Some thoughts from researcher Attila Chordash: "One strategy (call it Life Extension Gets Personal) to raise awareness for the idea and technology of healthy life extension is to publicly encourage life extension 'coming outs' on behalf of mainstream celebrities ... As a first target Craig Venter, the genomics pioneer seemed unconventional and free minded enough to approach with the idea of a LE blogterview. On the other hand I found definite signs of his interest in longevity and life extension suggesting that if Craig Venter had been given a technological-medical chance to extend his healthy lifespan significantly he would definitely not like to die due to accumulating functional declines associated with aging within the next, say hundred years. Maybe I am wrong here, maybe I am not but to figure this situation out I translated these signs into the following blogterview questions and tried to contact him in early December, 2007. So far I reached only his nice and diplomatic PR agent, who said that maybe we have a chance to get the blogterview done in the near future." Making this sort of modest effort is more than most people are doing - an excellent initiative.

An Overview of Metabolism, Damage and Aging (January 14 2008)
A good, long introduction to the way in which normal metabolic processes push you into aging and disease can be found at DiabetesHealth. Along the way, the article heaps praise on the practice of calorie restriction, which is usually a good way to know the writer has their head screwed on right: "At first glance, human centenarians would appear to have very little in common with calorie-restricted animals. After all, humans can eat what they want when they want, and many centenarians did just that. There is no evidence that centenarians followed a particular diet or even had particularly healthy life styles. Some centenarians smoked, some did not; some exercised regularly, some did not; and some were careful eaters, and some ate whatever they felt like. Despite the obvious differences, there are some striking similarities between caloric-restricted laboratory animals and free-living centenarians. Centenarians and calorie-restricted animals share a particular bio-metabolic profile that distinguishes them from their peers who die younger and sicker. We now know the common denominators that are found in almost all living beings - whether they are worms, mice, monkeys or humans - that defy the odds and live beyond their expected life span."

Point of Inquiry Interview With Aubrey de Grey (January 14 2008)
Point of Inquiry interviews biomedical gerontologist Aubrey de Grey: "Aubrey de Grey, PhD, is a biomedical gerontologist and Chairman and Chief Science Officer of The Methuselah Foundation. His major research interests are the role and etiology of all forms of cellular and molecular damage in mammalian aging, and the design of interventions to reverse the age-related accumulation of such damage. He has published extensively on these and other areas of gerontology, and is also Editor-in-Chief of Rejuvenation Research, the only peer-reviewed academic journal focusing on intervention in aging. He is the organiser of an ongoing series of conferences and workshops that focus on the key biomedical research relevant to SENS, and he also oversees the Methuselah Foundation's growing sponsorship of SENS research worldwide. In this conversation with D.J. Grothe, Aubrey de Grey explains aging, and the SENS (Strategies for Engineered Negligible Senescence) program that seeks to reverse aging in our lifetime. He explains how his work is, and is not, continuous with 'transhumanism.' He addresses challenges the medical and scientific establishment have brought against his work, and how his project is different than the quackery so widespread in the anti-aging movement. He also discusses some of the social and existential problems that ending aging may create for our civilization."



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