LONGEVITY MEME NEWSLETTER
February 11 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.
- Engineered Longevity
- What We Know About Inflammation and Aging
- Latest Healthy Life Extension Headlines
Noteworthy increases in the gene-engineered longevity of laboratory animals have been in the popular science press of late. Following closely on the heels of last week's 50% boost to mouse life span, the folk who managed a tenfold increase in nematode life span (in the species C. elegans) have made their work more accessible to those of us without journal subscriptions:
"Reis' team discovered that a mutant in the insulin/IGF-1 pathway of C. elegans slows development but ultimately produces adults he described as 'super survivors,' able to resist levels of toxic chemicals that would kill an ordinary worm. Although the adult lifespan of C. elegans is normally only two to three weeks, half of the mutant worms were still alive after six months, with some surviving to nine months. ... These worms continue to look and act like normal worms of one-tenth their age."
Insofar as human longevity science goes, I suspect that the most important near-term result of all this early work in longevity gene engineering will be to get people fired up about investing in serious efforts to extend human life span - and hopefully fired up about removing the regulatory roadblocks that hold back progress towards that goal:
WHAT WE KNOW ABOUT INFLAMMATION AND AGING
A brief, high-level tour of present scientific thought on chronic inflammation in the context of aging can be found in this Fight Aging! post:
"As I might have mentioned once or twice, chronic inflammation stretched over the years causes damage, suffering and death. It's a significant component of the processes of degeneration that accompany aging."
But inflammation is also a vital component of healthy biochemistry:
"Considering inflammation as a 'causative agent in aging' belies the underlying mechanisms whereby the acute inflammatory response is necessary for survival, and efforts to reduce and control the inflammatory response leave the host susceptible to infectious agents and improper healing. ... It is more appropriate to target the underlying initiating conditions than the inflammatory process that ensues and treat the basic mechanisms of disease rather than interfere in a very important protective mechanism of the host."
This is a good encapsulation as to why an emphasis on patching problems at the point of urgency has limited utility. When it's all you can do, you do it because it's better than nothing. But turning down inflammation, the goal of a major arm of the drug research community these days, is not reaching deep enough into the chain of cause and effect if the goal is to reverse the contribution of inflammation to aging. It seems likely that the place to look for a better way forward is in attempts to block and reverse the long-term effects of cytomegalovirus (CMV) on the immune system:
Chronic inflammation with age is likely a sign that the immune system is overtaxed by CMV and other lesser herpesviruses, run far past its point of evolutionary optimization. Like the worn thermostat, it can no longer operate at the correct level for the circumstance. Fortunately, humanity is the species that sees any form of limit as a giant red flag to be charged. Limits on the immune system will go the way of many other limits conquered by medical science:
The highlights and headlines from the past week follow below.
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LATEST HEALTHY LIFE EXTENSION HEADLINES
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/
1% For Longevity Research (February 08 2008)
A generous donation by one of the founders of startup company Mediox: "The co-founder and president of Mediox, Inc., Alex Zhavoronkov, today announced a donation of portion of his company stock representing 1% of company total issued shares to the Methuselah Foundation. ... From the inception of Mediox, our team decided to model the company after Google and benchmark their best practices. This 1% donation to the Methuselah Foundation is our way of giving back to society. Helping extend human lifespan indefinitely has been my goal for many years. The Methuselah foundation has a strategy and the tools required to combat aging and we are proud to have them as shareholders of Mediox Inc. ... Over the past several years many prominent businessmen including Peter Thiel, founder of PayPal, Jay Walker, founder of Priceline, William Haseltine, founder of HGS, donated to the Methuselah Foundation to help accelerate anti-aging research."
Still Underestimating (February 08 2008)
Judging by this Gobal Pensions article, the big players in the insurance and risk markets are still betting against even the present rate of increase in healthy longevity: "Nearly half of the FTSE 100 companies amended the mortality assumption of their pension scheme ... They had become increasingly conscious of longevity and investment risk in current markets. ... Research into annual reports showed companies now estimated current pensioners would live an average extra 16 months but those retiring in 15 years time would live an extra 21 months. ... The longevity changes are, by contrast, concrete and in the here and now, and reflect an expectation of increased real cost of benefits due to members living longer, rather than a change in the approach to measurement." At present, medical science is adding one year every five years - and we are in the early years of nothing less than a revolution in the capabilities of biotechnology. That 21 month figure seems a fair way below the mark, and I predict a great deal of money will be lost in these industries in the decades ahead.
Methionine Restriction and Longevity (February 07 2008)
A fair weight of research suggests that lower intake of methionine plays a large role in the effects of calorie restriction: "Available information indicates that long-lived mammals have low rates of reactive oxygen species (ROS) generation and oxidative damage at their mitochondria. On the other hand, many studies have consistently shown that dietary restriction (DR) in rodents also decreases mitochondrial ROS (mtROS) production and oxidative damage to mitochondrial DNA and proteins. It has been observed that protein restriction also decreases mtROS generation and oxidative stress in rat liver, whereas neither carbohydrate nor lipid restriction change these parameters. This is interesting because protein restriction also increases maximum longevity in rodents (although to a lower extent than DR) and is a much more practicable intervention for humans than DR, whereas neither carbohydrate nor lipid restriction seem to change rodent longevity. Moreover, it has been found that isocaloric methionine restriction also decreases mtROS generation and oxidative stress in rodent tissues, and this manipulation also increases maximum longevity in rats and mice. In addition, excessive dietary methionine also increases mtROS generation in rat liver. These studies suggest that the reduced intake of dietary methionine can be responsible for the decrease in mitochondrial ROS generation and the ensuing oxidative damage that occurs during DR, as well as for part of the increase in maximum longevity induced by this dietary manipulation."
Grow Your Own Replacement Parts (February 07 2008)
CBS News looks at the state of tissue engineering: "From blood vessels to muscle tissue, Atala and his team at Wake Forest University believe that in theory anything inside the body can be grown outside the body ... And it's real: They've made 18 different types of tissue so far. ... In a clinical trial at Thomas Jefferson Hospital in Philadelphia, a patient got a bladder transplant - with a new bladder grown from her own cells. ... the company also plans to mass-produce blood vessels and kidneys ... When people ask me 'what do you do,' we grow tissues and organs. We are making body parts that we can implant right back into patients ... Scientists believe every part of the body has cells capable of regeneration - all researchers need to do is isolate those cells and coax them to grow. ... What's coming from this technology is a future of highly personal, mail-order medicine, where in order to cure your disease, your doctor will order you a replacement organ or body part and it will be custom made for you, using your own cells. ... In regenerative medicine, I think it is similar to the semiconductor industry of the 1980s. You don't know where its going to go, but you know its big."
Kirkwood on Longevity and Aging (February 06 2008)
Colin Farrelly notes a Tom Kirkwood piece on longevity and aging: "The increase in human life expectancy over the past ten years has taken both scientists and the population generally by surprise. Until recently, demographers were confidently predicting that once the gains made by reducing mortality in early and middle life had reached completion, growth in longevity would stop and we would see the fixed reality of the ageing process. This has not happened. ... The continuing increase in life expectancy, which in many countries advances by several hours per day, is one of humanity's most astonishing successes. ... Age is by far the biggest risk factor for a wide range of clinical conditions that are prevalent today. One might therefore presume that a major effort is being made to understand the ways in which ageing renders the elderly more vulnerable to pathology. Nothing could be further from the truth. There is a large number of medical research institutes around the world, many with a focus on one or more of the major age-related diseases - cancer, heart disease, arthritis or dementia. Yet only a tiny fraction of these carries out any research on the intrinsic contribution from the ageing process itself."
Bioinformatics and the Ticking Clock (February 06 2008)
A companion post to yesterday's link to GrailSearch expands on the challenge facing biogerontologists - and medical science in general for that matter: "In cellular immunology, for instance, there are about 100 billion peptide sequences to which the immune system can respond, each targeted by a small set of white blood cells, or T lymphocytes - as many types of T cells in one human being as there are stars in our Galaxy. Just a 100 billion eh? These insane types of numbers constantly whack us up-and-coming bioinformaticians in the head like the proverbial cartoon rake-to-forehead smackaroo. You get to the point that you simply shrug your shoulders, tell yourself there will be an indexed database for that dataset someday, and move on. But will there be a comprehensive set of biological databases in our lifetime? ... To really do this requires this being a primary research goal whereas most research efforts are simply focused on one very small task at hand with a limited research budget. The result is thousands of nonstandard databases and datasets being published all over the net with nobody really synthesizing the data. Our thinking needs to change in our approach to informatics and biology otherwise we'll keep doing the same work over and over. From an aging perspective, we just don't have time to let comprehensive aging models evolve from basic research as the data emerges."
The Golden Age of Biology (February 05 2008)
From GrailSearch, an enthusiastic look at the role of bioinformatics in the mainstream approach to tackling aging by manipulating genes and metabolism: "The golden age of biology is upon us. We have broken through what previously seemed like an impenetrable wall of complexity, size and scale by decoding the human genome and are now building the next generation of tools to tackle the subsequent set of challenges. The most significant of these hurdles is that of aging. It also happens to be humanity's most important problem to tackle as most human suffering stems from this unfortunate and unnecessary process. The best tool we have for understanding the complex biological networks of aging is computational theory, particularly machine learning and its application to Systems Biology. Computational horsepower via high-performance computing, machine learning algorithms and biological data are all reaching a point where the intersection of these will soon allow us to use computational systems approaches for developing predictive models that precisely illustrate how we can tweak biological networks to best affect the dreaded aging process."
Common Sense (February 05 2008)
Making the most of your natural, inbuilt capacity for longevity is nothing more than applied common sense. For many people, that common sense will make enough of a difference to healthy life span to live into the era of rejuvenation medicine and the repair of aging. Via CNN Money: "Challenge yourself to learn new things. Learn a language. Take up the violin. Crossword puzzles and computer games aren't going to do the trick. You're retrieving information you've got in memory. Learning, though, seems to change the brain - it seems to improve resiliency. ... Obesity and inactivity will kill you. Aim for 30 minutes of exercise a day, but even just 10 minutes will help. Our bodies will benefit from any exercise at any age. Even frail, bedridden 80-year-olds benefit from regular programs of light weight lifting. After exercising they had fewer complaints of pain or discomfort. ... We've got to rethink retirement. Unless you have health issues, there aren't a lot of good reasons to quit working at 65. Work gives structure and meaning to life, though you may not want to work the same long hours as when you were young." Make use of the capacities you have, or be prepared to see them wither away much faster than you'd like.
It's All About the Autophagy (February 04 2008)
The better known life extension mechanisms in lesser animals are all driven by changes in autophagy - or so say the autophagy specialists. It's true that the various hyperspecialized communities of modern biology are overly cloistered and ignorant of one another's research, but the autophagy researchers are assembling compelling evidence for this position: "Here we show that mutational inactivation of autophagy genes, which are involved in the degradation of aberrant, damaged cytoplasmic constituents accumulating in all aging cells, accelerates the rate at which the tissues age in the nematode Caenorhabditis elegans. According to our results Drosophila flies deficient in autophagy are also short-lived. We further demonstrate that reduced activity of autophagy genes suppresses life span extension in mutant nematodes with inherent dietary restriction, aberrant insulin/IGF-1 or TOR signaling, and lowered mitochondrial respiration. These findings suggest that the autophagy gene cascade functions downstream of and is inhibited by different longevity pathways in C. elegans, therefore, their effects converge on autophagy genes to slow down aging and lengthen life span. Thus, autophagy may act as a central regulatory mechanism of animal aging."
FirstScience Interview With Aubrey de Grey (February 04 2008)
FirstScience interviews biomedical gerontologist and radical life extension advocate Aubrey de Grey: "I always try to be quite forthright and say that the technologies we develop within the next 30 years will probably only give us another thirty or so years of extra life. It's just that that extra thirty years is a hell of a long time for the technology to grow further. It's a little bit counter intuitive to people, because I often make an analogy with simple man-made machines and that we need to perform repair and maintenance on them. As in the case of cars, it's the rare car that gets a level of maintenance which can keep it going for a hundred years. The difference in the case of the human body is that we don't have a plan for this sort of maintenance. And so we don't know what to do quite so well, and we have to boot-strap to that point even though the machine (the human body) already exists. Once people understand this concept, it does help them to be much more sanguine about the possibility that we might be able to go from the point we are at in this moment – being able to do virtually nothing about aging – to effectively indefinite life spans within a few decades, which otherwise, would just make no sense at all." The path to extreme longevity is a bootstrap process of incrementally better repair technologies for the damage of aging. You don't have to fix everything - you have to fix enough to stay in good health for the next, better technology to be developed.