Calorie restriction molecular mechanism found

June 03, 2004
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Calorie restriction molecular mechanism found


Fasting and Calorie Restriction

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Calorie restriction molecular mechanism found
Research in mouse tissue conducted by MIT professor of biology Leonard Guarente and colleagues, published in the online version of Nature ( on June 2 2004, found that calorie restriction effects a protein that controls whether fat is stored or released. Calorie restriction has been found to extend the lifespan of every species in which it has been tested, and many humans have adopted the diet in hope of extending their own lives. The protein is the product of the mammalian gene sirtuin 1 (Sirt1), similar to the SIR2 gene that has been found to mediate the effects of calorie restriction in yeast. When Sirt1 senses short-term famine, such as is mimicked by calorie restriction, it turns off the receptors that keep fat in fat cells, and fat is released or metabolized rather than stored. The authors explain that the “Sirt1 protein activates a critical component of calorie restriction in mammals; that is, fat mobilization in white adipocytes. Upon food withdrawal the Sirt1 protein binds to and represses the genes that are controlled by PPAR-gamma, the fat regulator.”

Dr Guarante elaborated, “The ability of fat cells to sense famine and release the fat is regulated by this gene. We like to think this applies to people as well as mice, but we don’t know for sure. If we could make this happen in people, it wouldn’t just make them live longer; it might also help prevent diseases of aging, like cancer, diabetes and heart disease . . . If we could make a drug that would bind to Sirt1 and fool the body into thinking that it needed to release that fat, then maybe people could get the benefits of calorie restriction without the side effects.”

Because white adipose tissue makes hormones, including leptin which controls satiety, Guarente speculates that fat cells also tell the body how fast to age. He added, “Conversely, fewer fat cells tell the body that it’s time to hunker down for survival. This means that evolutionarily speaking, fat plays a very important role.”


Fasting and calorie restriction
Claims that various nutritional interventions can extend life span are manifold, but some are grounded in greater credibility than others. Among regimens debated, gerontologists often agree that Caloric Restriction with Optimal Nutrition (CRON) offers the greatest likelihood of succeeding.

According to Ben Best, a CRON advocate, "From an evolutionary or survivalist point of view, many of the observed effects of CRON make a great deal of sense." When food is abundant an animal grows large, matures quickly, and reproduces. When food is scarce, less energy is devoted to growth, basal metabolism, or reproductive capacity. Energy is maintained for muscular action, which is most important for survival.

According to the Harvard Medical School, calorie restriction has been shown to increase longevity in organisms ranging from yeast to mammals (Bluher et al. 2003). Researchers at the University of Texas Health Science Center (San Antonio) explain that the remarkable effects of restricting food intake to 50 to 70% of that eaten by ad lib-fed rodents appears to occur through three biological mechanisms: (1) reduction in oxidative damage; (2) modulation of glycemia and insulinemia; and (3) hormesis (a beneficial biological action from a factor or agent that is generally perceived as detrimental; life span extension by dietary restriction is an example of hormesis) (Masoro 1998, 2000).

Unfortunately, at least a 30% reduction in calories appears necessary to realize a significant health advantage from dietary restrictions. According to Richard Miller, associate director for research at the University of Michigan Geriatrics Center, such austerity requires a psychological profile that only one person in 1,000 possesses. Thus, according to Miller, "The best objective may not be to develop another diet that people will not follow but rather to concoct a pill or potion that mimics the beneficial effects of calorie restriction" (Taubes 2000). For example, a new agent, which mimics the function of a compound called PPAR-delta, seems to provide similar benefits to calorie restriction (at least in monkeys).

The classic American daily diet contains about 3,000 calories (men) and 2,000 calories (women). It is subsequently difficult to obtain sufficient nutrients when receiving only 1,500 calories per day. Nutrients often in short supply (in order of scarcity) are: zinc, vitamin E, copper, magnesium, iron, niacin, vitamin B12, pantothenic acid, calcium, riboflavin, folacin, vitamin A, vitamin B6, thiamine, and vitamin C (Best 1995). Thus, a number of supplements may work synergistically with calorie restriction to further tip the odds in favor of longevity.

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For longer life,

Dayna Dye
Editor, Life Extension Update
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