Longevity Meme Newsletter, August 20 2007

August 20 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 Week of Science at Fight Aging!
- Discussion
- Latest Healthy Life Extension Headlines


A great deal of what takes place in modern biomedicine is relevant to healthy life extension, even if not directly so. Better tools, more knowledge, and greater capabilities of medical technology - all feed into future growth and progress in living longer. The work of today is the foundation of tomorrow.

That said, this foundation of the future usually looks pretty ragged and confusing while it is being produced. Progress is built upon argument, debate, hypothesis and the defeat of evidence by better evidence; it's a dynamic, messy, intricate and detailed human process.


"if the hypothesis is, 'compounds that activate sirtuins will act as pharmacological mimetics of life-extending Calorie restriction in humans,' then I would say that it is outside of the realm of science, and into the realm of science fantasy, until someone shows me the slim, genetically-normal, 45-month-old, fully-fed but sirtuin-activated mouse."


"Another research group has just discovered that Wnt is able to suppress mouse stem cell activity because as mice age their bodies make less of another protein called klotho. Well, klotho restrains Wnt and the absence of klotho causes Wnt to suppress stem cell division. ... You might think hey, why not deliver klotho hormone replacement therapy to slow or reverse cellular aging?"


"From the perspective our own long-term future as living beings, an understanding of how the mind works - or rather how the biology of the brain supports and enables the mind - is vital. ... It is your foundation and self, plain and simple. There can be no wholesale replacement of tissue, and so the risk of long-lasting roadblocks and tough periods in rejuvenation research for the brain is a serious threat."


"As time moves on, scientists continue to add weight of evidence to demonstrate that ever smaller amounts of excess body fat are in fact quite bad for your health and longevity over the years ... One of the many ways in which calorie restriction benefits healthy longevity is no doubt through minimizing this sort of age-related damage - but avoidance of damage scales with avoidance of fat ... Pick the level that works for you, but why damage yourself unnecessarily?"


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/

Video: Do You Want To Live Forever? (August 18 2007)
Via the Immortality Institute forums, I note that "Do You Want To Live Forever?" is now up at Google Video: a "Channel 4 documentary following the revolutionary life-extension and immortality ideas of this somewhat eccentric scientist Dr. Aubrey de Grey ... This show is all about the radical ideas of a [biomedical gerontologist] called Aubrey de Grey who believes that, within the next 20-30 years, we could extend life indefinitely by addressing seven major factors in the aging process. He describes his work as Strategies for Engineered Negligible Senescence (SENS)." I've concluded that "eccentric" actually means "has ideas I would never have" in common parlance. In a world of people who accept the status quo - no matter how terrible - and barely look beyond their noses, we need more visionaries, iconoclasts and driven, unreasonable people. They are the source of progress. The video is well-regarded by the folk at the Immortality Institute; you should take the time to watch.

Genetic Determinants of Human Life Span (August 17 2007)
Of interest today, a paper from Barzilai et al at the open access journal PLoS Genetics: "Human geneticists have only recently begun to use the tools of linkage analysis and association studies to identify alleles contributing to exceptionally long life spans. Interesting candidates have emerged from these studies. There is virtually no information, however, on the genetic basis of differential rates of decline in well-defined physiological functions among human populations. We shall argue that such studies, particularly those that are initiated in middle age, before the onset of complicating comorbidities, should have a high priority for research, as they would have the potential to discover genes that impact on rates of aging within various organ systems. ... Parents of centenarians (born in 1870) were shown to have approximately nine times the odds of living to the tenth decade as compared to controls. Siblings of centenarians were shown to have up to an 18-fold increase in the chance of achieving a similar age. Such data have raised the possibility that some specific genetic modulators of aging in humans can be identified using such populations, and that conserved pathways for exceptional longevity might thus be validated."

The Theft of Self-Damage (August 16 2007)
Why spend time and resources in activities you know significantly damage your health? Doing so steals the most valuable possession possible - years of healthy life that might have let you reach an age of radical life extension - from the person you will one day be. You're picking your own pocket, cutting your future self short. For example: "The smoke of cigarettes represents an important accelerator of the aging process, both directly through complex mechanisms mediated prevalently by excessive formation of free radicals, and indirectly by favoring the appearance of various pathologies ... smoke compromises not only life expectancy, but also the quality of the life, favoring the occurrence of non-autosufficiency. Smoking is an important risk factor for many diseases, such as cancer, cardiovascular and respiratory diseases. ... Non-smokers have a much higher life expectancy than smokers, and the suspension of smoking is accompanied, even in the elderly, by an increase in the survival time due to the reduction of smoke-induced biological damage. ... Among [centenarians], smoking is extremely rare, and even when it occurs among them, it is correlated almost exclusively to bad health conditions and non-autosufficiency, indicating that it compromises health status and the quality of life even in extremely long living subjects."

No-one Dies of "Old Age" (August 16 2007)
From Courant.com: "Old people die, but they don't die of old age ... Organs wear down, diseases catch up; there's always a specific reason for a person's death. Though it's assumed that a centenarian didn't die in a rock-climbing accident, vague terms such as 'old age' don't help disease research. ... You're not trying to cure old age, you're trying to cure the conditions that caused the death." Which is at once the right and the wrong focus; right in that there should be no mystery left to aging once the biotech revolution is in full swing - every stone will be turned, every biochemical process recorded, every cellular change catalogued. But this focus is wrong in that we should not fixate on the end stage conditions if we want to make rapid progress in extending healthy life. Rather we should look for common forms of change and damage, and seek to repair them early and often. Our bodies are complex machinery, and the rules of maintenance apply here too. No machinery can last forever when left alone, but effective repair and preventative care can continue for so long as you care to do so - we just haven't developed the necessary technologies to do this for the human body. Yet.

Fabricating Bone (August 15 2007)
Inkjet printing and rapid prototyping technologies are finding their place in the field of tissue engineering. Fabrication of bone, for example, is moving forward nicely. From LiveScience: "First, the patient's actual bone structure is scanned with X-ray and CT scanners. The resulting data is combined to make a three-dimensional computer model of the bone; a set of cross-sections is sent to the special 3D inkjet printer. The 3D inkjet printer prints onto thin layers of powdered alpha-tricalcium phosphate (alpha-TCP); the printer 'ink' is a water-based polymer that hardens the alpha-TCP. Successive laydowns of powder and polymer 'prints out' the bone cross-sections to an accuracy of one millimeter. The resulting artificial bone is lightweight and porous; very similar to the original human bone used as a model ... the new artificial bones created from the alpha-tricalcium phosphate powder and polymer are ten times stronger than earlier implants made from hydroxylapatite ... Researchers [have] performed trials on ten people in the past year and a half [and] hope to make the technology commercially available by 2010."

More Progress In Repairing Mitochondrial DNA (August 15 2007)
As I'm sure you're all aware, mutations of mitochondrial DNA are an important form of age-related damage - any strategy for extending healthy life span must either repair this damage or make it irrelevant. Here, the Daily Mail has more news on repair efforts: "Defects in this mitochondrial DNA are blamed for a range of rare genetic diseases, including some forms of diabetes, blindness and heart problems. They have also been linked to ageing - suggesting that fixing the flaws could slow down the onset of old age. ... by labelling the functional genes with an "address code" - which effectively tells them where to go - French scientists have succeeded in smuggling them inside the mitochondria. Once there, the pair of genes repaired the damage behind a rare form of blindness and a muscle wasting disease ... In time, the same approach could be used to create injections of genes that will erase flaws thought to be linked to the ageing process. However, while this might slow down ageing, it would not halt it completely, as mitochondria are just one of many factors involved in the ageing process."

Sarcopenia As Dietary Issue (August 14 2007)
Sarcopenia, age-related muscle loss, is well known as a common result of aging - and the resulting lack of exercise hastens age-related decline in other ways. Scientists have demonstrated in recent years that adding the amino acid leucine to the diet prevents this progression, based upon a theory of age-related defects in protein machinery. Here, ScienceDaily notes a more general dietary theory, that the elderly consume less protein: "Since nutritional studies show that many elderly individuals eat less protein than the average person, researchers have reasoned that if the elderly simply increased their protein intake, they might slow down muscle loss -- as long as old age doesn't inherently interfere significantly with the ability to make muscles out of the protein in food. ... We wanted to know if there is some reason your grandmother's body, for example, can't stimulate muscle growth in response to eating the same protein-rich meal that you eat, which might over time contribute to muscle loss ... older bodies are just as good as young ones at turning protein-rich food into muscle." Which is interesting when compared with several lines of work suggesting that there are age-related issues with the process of building muscle - it goes to show just how much work is left to do in even the seemingly simple aspects of our biochemistry.

The Mitochondrial Numbers Game (August 14 2007)
This paper offers a reminder that nothing in biology is as simple as we'd like it to be: "Mitochondrial dysfunction has long been considered a key mechanism in the ageing process but surprisingly little attention has been paid to the impact of mitochondrial number or density within cells. Recent reports suggest a positive association between mitochondrial density, energy homeostasis and longevity. However, mitochondrial number also determines the number of sites generating reactive oxygen species (ROS) and we suggest that the links between mitochondrial density and ageing are more complex, potentially acting in both directions. The idea that increased density, especially when combined with mitochondrial dysfunction, might accelerate ageing is supported by a negative correlation between mitochondrial density and maximum longevity in an interspecies comparison in mammals, and by evidence for an intimate interconnection between cellular ROS levels, mitochondrial density and cellular ageing. ... We hypothesise that increased mitochondrial biogenesis, and possibly also impaired degradation and segregation of mitochondria, if occurring as adaptation to pre-existing mitochondrial dysfunction, might aggravate ROS production and thus actively contribute to ageing."

Repairing the Amyloid Removal Process (August 13 2007)
That amyloid levels in the brain are very dynamic is a comparatively recent discovery. Buildup of amyloid beta in Alzheimer's is likely not a matter of slow accumulation, as the amyloid material is constantly generated and destroyed in a matter of days, but rather slow failure of the active mechanisms for removing this toxic substance. Some researchers are taking aim at this process, as noted at ScienceDaily: "The team concentrated its efforts around a protein known as sLRP (soluble low-density lipoprotein receptor-related protein). The team discovered that in healthy people, the protein binds to and neutralizes anywhere from 70 to 90 percent of the amyloid-beta that is circulating in the body. ... Levels of sLRP in people with Alzheimer's were about 30 percent lower than in healthy people, and the sLRP that was present was almost three times as likely to be damaged compared to the same protein in healthy people. ... Zlokovic's group decided to try to reduce amyloid-beta levels in the body by synthesizing an altered, super-potent form of sLRP ... In blood samples from patients with Alzheimer's disease, the modified version of sLRP, known as LRP-IV, soaked up and virtually eliminated amyloid-beta. ... in mice with features of [Alzheimer's] LRP-IV lowered the levels of amyloid-beta in their brains by 85 to 90 percent."

Visualizing the Biochemistry of Aging (August 13 2007)
From GrailSearch, a look at aging from Legendary Pharmaceuticals, a company working on AGE-breakers. Don't miss the huge diagram of aging biochemistry: "Human life is supported by a complex network of biochemical substances and reactions which affect the physical state and vitality of the body and mind. Senescent changes can be seen in the rate and outcome of many of these reactions. However, many of these changes are secondary effects of senescence, rather than primary causes. ... John D. Furber of Legendary Pharmaceuticals has put together a visual model of aging referred to as 'The 2007 Network of Biological Interactions in Human Aging' that shows the interactions between various subcellular, cellular, extracellular matrix and organ system. This is a great representation of aging as it demonstrates no root cause but rather a network of problem areas that are interlinked. The goal of systems biology would be to flush this out in great detail allowing one to zoom in down to the specific genomic and proteomic components of aging."



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