Longevity Meme Newsletter, November 05 2007

November 05 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.



- Recent AGE-Breaker Research
- Ending Aging Hits Amazon Top 100
- Discussion
- Latest Healthy Life Extension Headlines


I've noticed an upswing in published research into breaking down or inhibiting production of advanced glycation endproducts (AGEs) of late. AGEs are a range of metabolic byproducts that gum up the works in your biochemistry, such as by sticking vital chemical compounds together so that they can't perform their role. The more AGEs in your system, the worse the damage they cause, directly contributing to age-related degeneration and disease:


A number of groups are at the stage of animal or early human trials with designed or discovered compounds, many focused on diabetes due to the increased level of AGEs associated with that condition, and the fact that regulatory agencies do not recognize aging as a disease - and thus will not approve a therapy designed to repair a cause of aging. For example, the AGE-breaker compound C36 has been evaluated on diabetic rats:


"Unfortunately, past evidence suggests that excitement over work in rodents should be muted at best - the history of ALT-711 or alagebrium demonstrates that different types of AGEs are important in shorter-lived mammals versus humans. So far, promising work in mice and rats has translated poorly into human therapies - in most cases, through trying to address the wrong AGEs."

Some more AGE research from the recent past:



"Ending Aging: The Rejuvenation Breakthroughs That Could Reverse Human Aging in Our Lifetime" briefly made it into the Amazon top 100 best sellers this past week, following wider distribution of a Washington Post article on biomedical gerontologist Aubrey de Grey and the Strategies for Engineered Negligible Senescence (SENS). Great news!


"I am encouraged that a hard science book can still attract a lot of attention in the marketplace of ideas, and pleased that a grounding in the SENS view of how to defeat aging will spread further as a result. The spread and discussion of these ideas is a necessary foundation for the process of raising significant further funding for ongoing SENS research. Both MitoSENS and LysoSENS projects are funded at present by donations to the Methuselah Foundation, but a wide range of other SENS-like or SENS-applicable work takes place out there in the world. We would like to see those research groups grow and attain the funding they deserve."

You can find out more about presently ongoing SENS research at the Methuselah Foundation website:



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/

A Million Optimizations Without Forethought (November 02 2007)
Let us count the ways in which biochemical processes, optimized through evolution for youthful health and reproductive success, interact poorly as they change with age, and thus cause pain and suffering. Here is one example of many from EurekAlert!: "Jason Dyck and his research team at the University of Alberta have been studying the types of fuels used by the heart in young and aged mice. The young healthy heart normally used a balance of fat and sugar to generate energy to allow the heart to beat and pump blood efficiently. However, as the heart ages the ability to use fat as an energy source deteriorates. This compromises heart function in the elderly. Interestingly, at a time when the heart is using less fat for energy, Dyck has shown that a protein that is responsible for transporting fat into the contractile cells of the heart actually increases. Based on this finding, Dyck proposed that the mismatch between fat uptake and fat use in the heart could lead to an accumulation of fat in the heart resulting in an age-related decrease in heart function." This being the age of biotechnology, they go on to engineer a mouse that doesn't suffer from this specific problem - but you get the idea. Aging is damage and change that causes disarry; repair or prevent the changes sufficiently well and you don't have to patch up after the disarray.

Biomechanisms of Limb Regeneration (November 02 2007)
LiveScience reports on progress in understanding how salamander biochemistry regenerates entire lost body parts: scientists "ran experiments in which they chopped off red-spotted newts' limbs and the attached nerves. The nerves are needed to stimulate the production of the nAG protein, so the nerve-severing essentially removed the newts' source of nAG. Then they zapped the cells of the now-exposed body region with electrical pulses so they could deliver little bundles of DNA carrying genes for the protein nAG. Within 30 to 40 days, the newts had regenerated their lost limbs, digits and all. However, the new limbs had less muscle mass than the original ones. Further lab experiments revealed the nAG protein - a molecule - works directly on the blastema cells, causing them to grow and divide. ... It essentially tells us that one single molecule is able to support the proliferation of blastema cells right from the start of regeneration all the way through to the formation of the digits." As the researcher notes, it is a solid step but many more steps are required before we humans will be regrowing damaged organs.

FuturePundit on the Repair of Aging (November 01 2007)
Thoughs from Randall Parker: "Aubrey [de Grey] believes (and FuturePundit agrees) that we can develop biotechnologies that will allow us to reverse aging and make us young again. This goal will be achieved within the lifetimes of at least some of the people currently alive. The sooner the general public realizes this the faster this goal will be realized. ... Aubrey thinks people are heavily invested in believing that death from aging is inevitable. This position made sense back when death from aging really was inevitable. Best to rationalize that aging is a good thing if there's nothing you can do about it. Make your peace and find reasons to be happy with what you can't change. But the rate of advance of biotechnology is accelerating with DNA sequencers and microfluidic devices becoming more powerful in ways analogous to the rate of progress with computers. We can strive for goals that used to seem unattainable. We should start trying to conquer aging. It is a solvable problem." Exactly right - and we can all jump in and help. You don't have to be a researcher to help to researchers make faster progress towards the defeat of aging.

A Gentle Reminder About the Fat (November 01 2007)
Even moderate excess weight is not a good thing for health and longevity over the long term, as the BBC reminds us: "The World Cancer Research Fund carried out the largest ever inquiry into lifestyle and cancer, and issued several stark recommendations. ... People with a Body Mass Index (BMI), a calculation which takes into account height and weight, of between 18.5 and 25, are deemed to be within a 'healthy' weight range. But the study says their risk increases as they head towards the 25 mark, and that everyone should try to be as close to the lower end as possible. There is no new research involved in this document: the panel examined 7,000 existing studies over five years." BMI is not a one size fits all measurement, but the general conclusions fit regardless of where exactly a sensible lifestyle choice - such as practicing calorie restriction - places you. Cancer is just one of many age-related conditions whose risk is strongly correlated with excess body fat over the years. Maybe the technology of tomorrow will be available in time to save you from the neglect of today. Equally, maybe it won't; is that something you really want to gamble on?

The Key to Parkinson's Disease? (October 31 2007)
An exciting discovery via ScienceDaily: researchers "have discovered the key brain chemical that causes Parkinson's disease ... Parkinson's disease occurs when some nerve cells in a part of the brain called the substantia nigra die or become impaired. Normally, these cells produce dopamine - a vital chemical that allows smooth, coordinated function of the body's muscles and movements. Scientists have long known that a key protein called alpha-synuclein plays a role in the development of Parkinson's disease. Alpha-synuclein is found throughout the brain - but in some people, the protein clumps together. This causes the death of the dopamine-producing cells, which in turn causes Parkinson's to develop. ... researchers discovered that dopamine itself actually plays a role in destroying the cells that produce it. In the process that leads to Parkinson's disease, dopamine is converted into a highly toxic chemical called DOPAL. Using test-tube, cell-culture and animal models, the researchers found that it is DOPAL that causes alpha-synuclein protein in the brain to clump together, which in turn triggers the death of dopamine-producing cells and leads to Parkinson's." It should go without saying that finding a key mechanism in this day and age will quickly lead into the design of therapies.

Washington Post Interview With Aubrey de Grey (October 31 2007)
The Washington Post interviews biomedical gerontologist Aubrey de Grey on healthy life extension research: "Aging consists of seven critical kinds of damage, according to de Grey. For example, unwholesome goo accumulates in our cells. Our bodies have not evolved means quickly to clean up "intracellular aggregates such as lipofuscin." However, outside our bodies, microorganisms have eagerly and rapidly evolved to turn this toxic waste into compost. (De Grey made this connection because he knew two things: Lipofuscin is fluorescent and graveyards don't glow in the dark.) By taking soil samples from an ancient mass grave, de Grey's colleagues in short order found the bacteria that digest lipofuscin as easily as enzymes in our stomachs digest a steak. The trick now is getting those lipofuscin-digesting enzymes into our bodies. That has not yet been done. But, de Grey says, comparable fundamental biotechnology is already in clinical use fighting diseases such as Tay-Sachs. So he sees it as merely an engineering problem. Examples like this make up the 262 pages at the center of 'Ending Aging.'"

Calorie Restriction and Mitochondrial Function (October 30 2007)
One way in which calorie restriction resists age-related issues with mitochondrial function in your cells is likely to be by encouraging autophagy, the process of recycling damaged cellular components - such as mitochondria, the power plants of your cells. Here, researchers note that one component of mitochondrial function, the malate-aspartate shuttle, declines with age, but is restored by calorie restriction: "Dietary restriction (DR) influences several physiological processes, retards the incidences and severity of various age-related diseases and extends lifespan of various animal species. The effect of DR on the activities of malate-aspartate shuttle enzymes [was] investigated in the liver and kidney of adult (5-months) and old (21-months) male mice. The results show that the activity [of the enzymes] is decreased significantly in the liver and kidney of old mice compared to adult ones. However, DR in old mice reverses significantly the enzyme activities to a level closer to adult animals. ... our results suggest that the late onset of DR in older mice reverses decline in malate-aspartate shuttle enzymes and that it may allow a better metabolic regulation in older animals." More evidence that it's never to late to start on calorie restriction - there are benefits to be had even if you are already aged.

Austad and Olshansky's Bet (October 30 2007)
Best Life Online looks at the well-known bet made between researchers Steven Austad and S. Jay Olshansky: "Olshansky didn’t think anyone was going to live to 150 anytime soon. But Austad was quite serious, and so the two men made a wager. They each put up $150, which Olshansky invested in a fund. The winnings will be handed out in the year 2150. If there is a 150-year-old alive on earth - someone of sound mind and body - Austad's descendants will get the pot, which Olshansky has calculated will grow to $1 billion thanks to his shrewd, but secret, investments. ... In the years since the bet, the two scientists have closely monitored new evidence, and, somewhat remarkably, neither has seen any reason to budge on the bet. ... In one corner, Austad, the swashbuckling adventurer and optimist, points to the accelerating pace of discoveries about aging: Scientists have identified the genes that prolong the lives of animals and discovered ways to switch those genes on, and researchers are launching pharmaceutical start-ups to create the first real antiaging drugs that could slow the cellular damage. In the other corner, Olshansky, the number-crunching realist, sees too many hurdles in the way. ... Despite their diverging perspectives on life expectancy, both men share a belief that science is finally catching up with aging, and this has ramifications for us all."

Stepping Towards a Cancer Vaccine (October 29 2007)
Researchers continue to work at developing a safe way to provoke the immune system into destroying cancer cells: "The discovery in the 1970s of unique sugars on cancer cells set scientists in search of a way to get the immune system to recognize and attack cells that express these cancer-associated sugars. Until now, however, the results have been less than spectacular. ... early cancer vaccines were created by linking the tumor-associated carbohydrate with a foreign protein. The immune system, perhaps not surprisingly, attacked the protein and the linker molecules, but generally left the carbohydrate alone. ... We needed to come up with a vaccine that does not give our immune system a chance to go after anything else but the tumor-associated carbohydrate ... When we tested our best vaccine we got really, really fabulous antibody levels that have never been seen before ... The vaccine has been successful in creating an antibody response that can kill cultured epithelial cells - those commonly involved in most solid tumors, such as breast and colorectal cancer - derived from mice and in stimulating an immune response in healthy mice. The researchers are currently testing the vaccine in mice with cancer, and [hope] to start phase I clinical trials in humans within a year." If medicine often looks like engineering, that's because it is.

An Interview With Aubrey de Grey (October 29 2007)
Machines Like Us interviews biomedical gerontologist Aubrey de Grey: "It'll almost certainly be a very long time indeed - many decades, possibly centuries - before we can completely repair everything that qualifies as 'damage' [and] therefore totally prevent aging. But luckily, we don't need to reach perfection in order to maintain our youth indefinitely, because a certain amount of damage - the sort of amount we have in early adulthood - is harmless, not causing any disease or debilitation. If we can develop reasonably comprehensive repair and maintenance therapies, that will buy time to develop even more comprehensive ones, thus buying more time to improve the therapies even more, and so on indefinitely, even if the therapies never achieve absolute perfection. "Longevity escape velocity" is the name I've given to the rate at which we would need to maintain this improvement of the therapies, following the initial breakthrough that gives middle-aged people maybe 30 extra years of healthy life."



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