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Life Extension, Caloric Restriction, and Scientific Philanthropy
by Leonid A. Gavrilov, Ph.D.
As the generation of Baby Boomers approaches retirement age, not all of them are prepared to fade away and die for the sake of Social Security solvency. Some people prefer to stay alive and active, and to enjoy life. But for how long? Well, as long as one can enjoy life without suffering from the ravages of old age and not be suicidal. This requirement brings us to the idea of healthy life extension, or “life extension” for short. Now is the right time for skeptics to jump into the discussion and say that this is not a new idea, and that it was a consistent failure for centuries. Well, the same could be said about human dreams to fly, before this dream eventually came true.
But is it possible to defeat aging? Can we go against the laws of Nature, or would it not be better to be reasonable and to accept the inevitable? Here the skeptics may jump into the discussion again with a quote by George Bernard Shaw (1856-1950):
"The reasonable man adapts himself to the world; the unreasonable one persists in trying to adapt the world to himself."
Well said indeed! Especially his last, inspirational sentence:
"Therefore, all progress depends on the unreasonable man."
In other words, yes, we may fail in most of our attempts to defeat aging, but it is a shame not to keep trying! Because if we don't try we will definitely not succeed!
Now what do we have at hand against aging so far? Some researchers believe that a powerful weapon is a caloric restriction (CR).
Cutting caloric intake by about 30% not only increases the lifespan of laboratory animals (mice, rats etc), but it also delays the onset of many age-related degenerative diseases including cancer and kidney failure. Moreover the CR animals are far more active and maintain their high physical activity for much longer periods of time when compared to control animals allowed to eat as much as they like. Although caloric restriction decreases fertility, it also extends the reproductive lifespan of the CR females, i.e., they maintain their reproductive capacity for longer periods of time. Finally, the CR animals have much more youthful appearance and behavior when compared to control animals. Numerous biochemical and physiological tests also indicate that many age-related changes are indeed delayed in CR animals. All these facts and observations are very important—they indicate that aging is not immutable, but on the contrary it can be postponed by very simple interventions.
It is important to emphasize that CR is not starvation or malnutrition -- the diet is rich in all nutrients including vitamins, minerals, proteins, etc., and it is only the amount of calories, which is decreased (less fat and carbohydrates). Also there is no need to restrict the diet permanently—the same effects could be obtained through intermittent feeding (say CR every other day), which is much easier to tolerate.
So, what about us humans? Should we start practicing CR? This is a topic where emotions run high, and reasonable discussions become difficult.
Some people claim that the usefulness of CR in humans has already been proven by natural experiments in such places as Okinawa (Japan), where CR was a traditional way of life, a place famous for its centenarians.
Others point to serious side effects of caloric restriction: the CR animals get chilled very easily, and they are far more vulnerable to infections. CR leads to the loss of muscles, and it impairs the process of wound healing. It certainly should not be recommended for people serving on active duty in the police or military, but perhaps scientists may try it, particularly if their work is a theoretical one. But even theoreticians may not like the increased irritability and decreased libido associated with CR.
If so, then why should we care about CR at all? Well, the answer to this question is that we can study the mechanisms of anti-aging action of CR, and this information may help us to develop drugs that mimic the positive anti-aging effects of CR, while freeing us of its negative side effects (see above) including feeling hungry most of the time. Also, in this case there will be no need to relay on strong willpower to comply with “this diet.” In other words, CR is not an ultimate solution to the aging problem, but rather a light at the end of a tunnel, which gives us hope and shows us possible avenues to explore.
To develop effective anti-aging CR mimetic drugs we need to know why and how CR works. Historically the following explanations for CR-induced life extension had been suggested and partially tested: retardation of growth (McCay et al.,1935), reduction of body fat (Berg and Simms, 1960), reduction of metabolic rate (Sacher, 1977), improved signal-to-noise ratio (Gavrilov and Gavrilova, 1991), altered glucose-insulin system (Masoro et al., 1992), up-regulation of programmed cell death, apoptosis (Warner et al., 1995), reduction of body temperature (Koizumi et al., 1996), attenuation of oxidative damage (Sohal and Weindruch, 1996), hormesis (Masoro, 1998), altered growth hormone - IGF-1 axis (Sonntag et al., 1999), increased physical activity (McCarter, 2000), increased turnover of body protein (Tavernakis and Driscoll, 2002), reduction of cell loss during aging (Cohen et al., 2004), and reduction of cell proliferation, responsible for DNA copy-errors and cancer promotion (Hsieh et al., 2005).
Some of these hypotheses on mechanisms of anti-aging effects of CR seem to be refuted by now (retardation of growth hypothesis and the reduction of metabolic rate hypothesis) while others are still fiercely debated (reduction of body fat hypothesis). Also, some hypotheses are not mutually exclusive (e.g., the improved signal-to-noise ratio hypothesis linked to reduced cell damage and the reduction of cell loss hypothesis). Recent studies suggest that caloric restriction prevents cell loss presumably through activation of sirtuin deacetylases, and such simple molecules as resveratrol stimulating the deacetylase activity of sirtuin proteins extend lifespan of nematodes and fruit flies. This gives hope that the development of effective anti-aging CR mimetic drugs may not be too far in the future.
If so, then what should we do now in order to survive by the time the genuine anti-aging drugs hit the market?
Recently the new 2005 "Dietary Guidelines for Americans" has been released by the U.S. Department of Agriculture (USDA) and U.S. Department of Health and Human Services (HHS). Based on these recommendations the USDA has developed an interactive website, which advises what amount and kind of food you should eat depending on your age, sex, and level of physical activity:
These new guidelines represent some progress, because they provide personalized recommendations (suggesting one of the 12 New Food Pyramids), and because they are more specific on the types of recommended food. The earlier guidelines failed to distinguish between a doughnut and a whole-grain roll, or a hamburger and a skinless chicken breast, and it did not make clear exactly how much of each type of food to eat. More detailed analysis of the suggested changes in new dietary recommendations is provided in the article "The 2005 Dietary Guidelines for Americans: What’s New?" at:
These new dietary recommendations have already received an endorsement from the American Cancer Society, American Diabetes Association, and American Heart Association, particularly for recommending increased consumption of fruits, vegetables and whole grains, and decreased consumption of saturated fats and trans fatty acids.
Yet, the enthusiasts of CR will be disappointed by these new guidelines, because they do not embrace the idea of 30% caloric restriction. This decision is of course perfectly understandable given the appetites of the American public and the food industry. What would be the point in suggesting the drastic, if not Draconian, measures when almost nobody would follow them? However even a conservative nutrition professor at New York University, Marion Nestle, who is not a CR enthusiast, is still critical of these new nutrition recommendations because "there's no 'eat less' message here."
However this criticism may become unsubstantiated now in view of the recent paradoxical findings that the lowest risk of death is observed among moderately overweight people, while being lean seems to be as bad as being obese. These new findings published in the April 20 issue of the Journal of the American Medical Association by Katherine Flegal and her colleagues at the Centers for Disease Control suggest that the detrimental effects of being overweight were grossly overstated in all previous studies. So, perhaps the new dietary guidelines are not as bad as the enthusiasts of CR could think.
Another group of people who may be disappointed by new dietary recommendations is the rapidly growing group of supercentenarians (people aged 110 years and above). These people seeking advice at the interactive USDA website will receive a note "Age must be 110 or younger" instead of any dietary recommendations for them. Is it assumed that people living that long do not need any further guidance?
One thing is for sure: The dietary guidelines alone will not allow us to defeat aging and to extend healthy lifespan beyond current longevity records. To achieve these goals we need concentration of the best minds and resources (a la the Manhattan project). These resources are unlikely to come from federal funding overstretched by war efforts, but perhaps they might come from wealthy visionaries like Larry Ellison, Bill Gates, Pierre Omidyar and George Soros, who could make a difference.
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Dr. Leonid Gavrilov has a Ph.D. in genetics and M. Sc. in chemistry, both from the Moscow State University, Russia. He is the founder of a new reliability theory of aging and longevity.He is a Principal Investigator on the scientific project "Biodemography of Human Longevity", funded by the National Institute on Aging (USA), and the author of over a hundred scientific publications on this topic.
To read more about Dr. Gavrilov please visit his Science Advisory Board profile,
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