Longevity Meme Newsletter, July 13 2009

July 13 2009

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.



- Calorie Restriction in Monkeys
- Rapamycin in Mice
- Another Look at Attitudes to Aging
- Discussion
- Latest Healthy Life Extension Headlines


Both of the research results that caught the eye of the press this past week involved the biochemistry of calorie restriction, eating fewer calories whilst still obtaining all the necessary nutrients. It extends the healthy lifespan and maximum lifespan of almost every species tested to date, and it looks like we can more confidently add a primate to that list:


"Studying aging in monkeys takes patience. Mice and rats only live for a couple of years, while these monkeys can live to 40, and the average life span is 27 years. Now that the surviving monkeys have reached their mid- to late 20s, the Wisconsin group could glean how calorie restriction was affecting their life span. Sixty-three percent of the calorie-restricted animals are still alive compared to only 45% of their free-feeding counterparts. For age-related deaths caused by illnesses such as cardiovascular disease and cancer, the voracious eaters died at three times the rate of restricted monkeys: 14 versus five monkeys, respectively."

The effects on the biochemistry of monkeys measured across the years look very much like the effects seen in humans in the CALERIE and other studies of human calorie restriction. The pile of evidence for noteworthy benefits for healthy humans practicing calorie restriction continues to grow:



The TOR (Target of Rapamycin) gene is of many components in the biological sensing, feedback, and control systems that determine how calorie restriction shifts the operation of metabolic processes into a healthier state. Researchers in recent years have been looking at sirtuin genes for the same reasons, but triggering TOR has produced greater benefits in a mouse study:


"Problems formulating the feed meant that the teams couldn't start the treatment until the mice were rather older than they had planned - 20 months of age, or the equivalent of about 60 years in human terms. As it happened, this delay was a fortuitous accident. Compared with the non-drug-taking group, the lifespans of the mice given rapamycin increased by up to 14%, even though they were middle-aged when treatment began. Their life expectancy at 20 months shot up by 28% for the males and 38% for the females.

"This is actually good enough to be worth running in the Rejuvenation Prize component of the MPrize for longevity science - it's about the same as the record for late onset calorie restriction started at that age. It has to be said that I'm surprised to see a presently available drug capture a similar level of additional longevity given the past few years of less stellar results from sirtuin-manipulating drugs."

Rapamycin isn't something you'd want to take, all things being equal - it's a strong immune suppressant, used in transplant surgery, and its recipients require constant medical supervision. The chief value here, I think, will be to focus more attention on the TOR gene as a point of manipulation for future designs of calorie restriction mimetic drugs.


The Speculist recently penned a good piece on why we still need to spend time convincing people that aging is a bad thing, and that alleviating the suffering and death caused by aging is no different from working to cure other diseases:


"Those who think taking on aging is a 'misuse' of medicine simply baffle me. If medical research came up with ways to eliminate cancer, heart disease, and diabetes, would anyone argue that those treatments represent a 'misuse' of medicine? Why is it bad for people to die from those things but okay for them to die from something else? Imagine somebody asks you to make a donation to the Juvenile Diabetes Research Foundation. Would you respond to that by saying, 'Why? So those diabetes sufferers can continue their lives of self-serving hedonism?'

"No, you would never say anything like that, because only a moral cretin of truly world-class proportions would even think anything like that. But turn those cancer or diabetes victims into old people, and they become fair game - people whose continued existence is just too inconvenient to bear - people who need to die already, who it would be a misuse of medicine to help."


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!




Modifying Mouse Metabolism (July 10 2009)
For all that I see modifying metabolism for the better to be harder and less beneficial than reversing damage caused by our existing metabolism, early technology demonstrations of modified metabolisms in mice are taking place. Here, h+ Magazine looks at one example: "We know plants and bacteria digest fats differently from humans, from mammals. Plant seeds usually store a lot of fat. When they germinate, they convert the fat to sugar to grow. The reason they can digest fat this way is because they have a set of enzymes that's uniquely present in plants and bacteria. These enzymes are called the 'glyoxylate shunt' and are missing in mammals. ... the researchers introduced genes for these enzymes from E. coli bacteria into cultured human cells and found that they increased the metabolism of fats in the cells. Rather than converting the fat into sugar as bacteria do, the cells converted the fat completely into carbon dioxide. ... The research team then introduced the genes into the livers of mice. While normal mice gain weight when put on a high-fat diet, [the] engineered mice 'remained skinny despite the fact that they ate about the same and produced the same waste' and were as active as their normal counterparts. They also had lower fat levels in the liver and lower cholesterol levels."

More On Methionine as the Crucial Amino Acid in CR (July 10 2009)
When will we see a very-low-methionine diet food range akin to those that exist for brand-name diet fads? The fact that such a thing doesn't exist and isn't being promoted to the hilt is yet another indication that the "anti-aging" marketplace cares little for science. Here's yet more evidence for methionine levels as one of the lynchpins of beneficial changes in metabolism caused by calorie restriction: "Protein or methionine restriction in the diet is known to decrease reactive oxygen species (ROS) production and mitochondrial oxidative stress and to increase maximum longevity in rodents, which could explain how these changes also take place in dietary restriction. However, it is not known whether restriction of other amino acids is also involved. To clarify this question, we studied the effect of restricting all the amino acids, except methionine ... the results obtained in the present study clearly show that the decrease in ingestion of only one molecule, methionine, causes the decrease in ROS production and oxidative damage to mitochondrial DNA that is observed in dietary restriction in relation to the decrease in the rate of aging."

Mass Manufacture of Immune Cells to Order (July 09 2009)
A mass infusion of immune cells is one strategy for dealing with a range of medical conditions - either by overwhelming the cause of the problem or by causing a specific response in existing immune system cells. But for this to become a reality, there must be a cost-effective way of manufacturing large numbers of immune cells: "Geron reports that dendritic cells (DCs) scalably manufactured from human embryonic stem cells (hESCs) exhibit normal functions of naturally occurring human DCs found in the bloodstream. These findings support the use of hESC-derived DCs in therapeutic vaccine applications for cancer and other infectious diseases ... When a dendritic cell presents an antigen to a T cell in vivo, it stimulates the T cell to produce inflammatory cytokines and causes antigen-specific T-cell proliferation. ... Geron was able to show that immature hESC-derived DCs could take up, process, and present antigens. Following maturation in the manufacturing process, the DCs were also able to migrate, produce proinflammatory cytokines, and induce specific immune responses to both tumor and viral antigens in vitro."

New Mprize Competitors Announced (July 09 2009)
The Methuselah Foundation gathers more competitors for the Mprize: "The Mprize offers researchers significant cash incentives in two categories: Longevity and Rejuvenation. Prizes are awarded for breaking the world record for the oldest-ever mouse and the most successful late-onset rejuvenation. The amount won is in proportion to the size of the fund and to the margin by which the previous record is broken. World class research teams from leading universities, including Harvard and MIT, are currently in competition for the prize. ... Tom Johnson, University of Colorado at Boulder is working with genetically diverse mice to identify variants and isolate the genes that contribute to a longer life to 'build' a mouse with a greater lifespan. The mice will live with environmental conditions and dietary restrictions conducive to longer life. Michal Masternak is expanding on the work of Andrzej Bartke (previous Mprize winner) also of the Southern Illinois University School of Medicine, breeding mice lacking both growth hormone and growth hormone receptor. They are observing increased insulin sensitivity, another factor related to sustained health and longevity."

The Dreaded Gothenburg Syndrome (July 08 2009)
From green light go: "What makes a disease a disease? Why isn't aging, a condition which results in the slow decline of the body, considered a disease? It seems so obvious. ... Another reason why people don’t recognize aging as a disease is because 100% of the population suffers from it. We just need one person with perpetual youth to ignite a massive outcry for an aging cure. Finally, we need a new word for the disease. 'Aging' is too confusing. People associate it with children growing, or with becoming wise and experienced. One could then use 'senescence' but that is a biological term. So what then can we use? Senectitudeitis? Enter Senectitudeitis, a disease characterized by: 1) Somatic degeneration, 2) Wrinkling of the skin, 3) Macular degeneration, 4) Muscular degeneration, 5) Sexual decline, 6) Increased risk of Cancer, and 7) the dreaded Gothenburg Syndrome where people come to identify with the disease as being a normal part of life." It wouldn't much matter whether we called aging a disease if not for the FDA, whose unelected and unaccountable bureaucrats will only approve treatments for diseases (when they're willing to take the political risk to approve anything at all, that is), and who do not recognize aging as a disease. In a world without the FDA standing athwart progress to cry "halt!", who would care what we called aging?

More on Alzheimer's Immunotherapy (July 08 2009)
An illustrative release via ScienceDaily shows how rapid advances in biotechnology are leading to a flood of new information on our biochemistry, here on the interaction of Alzheimer's disease and the immune system: "Alzheimer's disease is characterized by the build-up of amyloid plaques in the brain. These are large aggregations of a protein breakdown product, or peptide, called A-beta. Many experiments have shown that immunization with A-beta can reduce the formation of amyloid plaques. Clinical trials now underway are exploring whether this can safely produce cognitive benefits in Alzheimer's patients, while other trials are treating patients directly with antibodies to A-beta. ... Other studies have found antibodies against A-beta, but nobody has ever done a large-scale analysis using hundreds of different samples and almost a hundred different peptides to look for what's already in people's bodies ... investigators customized microarrays containing close to 100 different peptides apiece, including A-beta and several of its metabolized, modified, and mutant forms. ... They observed antibodies targeting many forms and aggregation-states of A-beta in both healthy and diseased subjects' blood ... They then showed that overall levels of these antibodies decline with age and, in those with Alzheimer's, with advancing stages of the disease."

An Advance in Controlling Neurons (July 07 2009)
Medicine is as much the quest to control our cells (and their signalling mechanisms) as anything else. Here is a small step on the way to both controlling errant cells in our brains, and ultimately learning how to replace them with something more durable: "The methods that are currently used to stimulate nerve signals in the nervous system are based on electrical stimulation. Examples of this are cochlear implants, which are surgically inserted into the cochlea in the inner ear, and electrodes that are used directly in the brain. One problem with this method is that all cell types in the vicinity of the electrode are activated, which gives undesired effects. Scientists have now used an electrically conducting plastic to create a new type of 'delivery electrode' that instead releases the neurotransmitters that brain cells use to communicate naturally. The advantage of this is that only neighbouring cells that have receptors for the specific neurotransmitter, and that are thus sensitive to this substance, will be activated. ... The ability to deliver exact doses of neurotransmitters opens completely new possibilities for correcting the signalling systems that are faulty in a number of neurological disease conditions."

Kurzweil on Engineering Away Aging (July 07 2009)
Here Ray Kurzweil responds to views expressed recently by aging researcher Leonard Hayflick: "Entropy is not the most fruitful perspective from which to view aging. There are varying error rates in biological information processes depending on the cell type and this is part of biology's paradigm. We have means already of determining error-free DNA sequences even though specific cells will contain DNA errors, and we will be in a position to correct those errors that matter. The most important perspective in my view is that health, medicine, and biology is now an information technology whereas it used to be hit or miss. We not only have the (outdated) software that biology runs on (our genome) but we have the means of changing that software (our genes) in a mature individual ... Our intuition is linear so many scientists, such as Hayflick, think in linear terms and expect that the slow pace of the past will characterize the future. But the reality of progress in information technology is exponential not linear. My cell phone is a billion times more powerful per dollar than the computer we all shared when I was an undergrad at MIT. And we will do it again in 25 years. What used to take up a building now fits in my pocket, and what now fits in my pocket will fit inside a blood cell in 25 years."

Atheletes Live Longer, Probably the Exercise (July 06 2009)
An observation from the demographics of one of the groups most likely to be found exercising: "The health benefits of leisure-time physical activity are well known, however the effects of engaging in competitive sports on health are uncertain. This literature review examines mortality and longevity of elite athletes and attempts to understand the association between long-term vigorous exercise training and survival rates. Fourteen articles of epidemiological studies were identified and classified by type of sport. Life expectancy, standardised mortality ratio, standardised proportionate mortality ratio, mortality rate, and mortality odds ratio for all causes of death were used to analyse mortality and longevity of elite athletes. It appears that elite endurance (aerobic) athletes and mixed-sports (aerobic and anaerobic) athletes survive longer than the general population, as indicated by lower mortality and higher longevity. Lower cardiovascular disease mortality is likely the primary reason for their better survival rates. On the other hand, there are inconsistent results among studies of power (anaerobic) athletes. When elite athletes engaging in various sports are analysed together, their mortality is lower than that of the general population. In conclusion, long-term vigorous exercise training is associated with increased survival rates of specific groups of athletes."

The Challenges of Testing Calorie Restriction in Flies (July 06 2009)
Never work with children and animals, or so they say. Even simple concepts such as calorie restriction (CR) can produce all sorts of challenges when it comes to designing experiments. Here, a researcher uses more rigor to show that protein restriction works to extend fly life while calorie restriction doesn't. "recent studies investigating the role of nutrients have challenged the role of CR in extending longevity. Fuelling this debate is the difficulty in experimentally disentangling CR and nutrient effects due to compensatory feeding behaviour. We quantified compensatory feeding by measuring the volume of solution imbibed [in the] Queensland fruit fly ... We restricted flies to one of 28 diets varying in carbohydrate:protein (C:P) ratios and concentrations. On imbalanced diets, flies overcame dietary dilutions, consuming similar caloric intakes for most dilutions. The response surface for lifespan revealed that increasing C:P ratio while keeping calories constant extended lifespan, with the maximum lifespan along C:P ratio of 21:1. In general, lifespan was reduced as caloric intake decreased. ... Our results 1) demonstrate that compensatory feeding can overcome dietary dilutions, 2) reveal difficulties with methods presenting fixed amounts of liquid diet, 3) illustrate the need to measure intake to account for compensatory feeding in DR studies, and 4) highlight nutrients rather than CR as a dominant influence on lifespan." I'd wait for further confirmatory studies before taking this as read.



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