Calorie restriction started at any age may prolong life In research funded by BioMarker Pharmaceuticals and the Life Extension Foundation, published in the March 22 2004 online early edition of The Proceedings of the National Academy of Sciences, Steven Spindler PhD and colleagues from the University of California at Riverside found that caloric restriction started late in life prolongs life span in mice. It had previously been believed that calorie restriction, a proven life-extending therapy that involves lowering calories without inducing malnutrition, must be started in youth to be effective. In the current research, the team found that mice, like fruit flies, that began calorie restriction in late middle-age benefited from it almost immediately.
In the first study, a long-lived strain of mice were fed a control diet or a diet restricted in calories by 40 percent less than normally required by typical mice. The diets were started at nineteen months of age, which is a few months before the onset of age-accelerated death for this species. Mice were checked daily, and autopsies performed upon their deaths. A second experiment fed mice control or calorie restricted diets beginning at seven months of age. At the approximate age of 34 months, gene expression studies of the liver were conducted.
The first study found that within two months of the initiation of the diets, the rate of age-associated mortality decreased three-fold in the restricted group, with the average time to death increasing 42 percent. Maximum lifespan was extended from 37.6 to 43.6 months. The cause of death for both groups of mice was mainly tumors, however the onset and growth of tumors was delayed in the calorie restricted mice.
At the conclusion of the gene expression study, calorie restricted mice showed the same patterns of liver gene expression as mice that began calorie restriction at young ages. In a group of mice that were taken off the restricted diets, 90 percent of this gene expression returned to previous patterns within eight weeks.
Dr Spindler told Life Extension that the findings in this mouse study may be true for humans as well, suggested by this and other studies. He added, “We found that the gene expression changes produced by caloric restriction occur rapidly, and are closely linked with its health benefits. This means we can relatively rapidly screen for pharmaceuticals which reproduce the gene expression effects of caloric restriction in animals, and have a reasonable expectation that these same pharmaceuticals may induce some or all of the beneficial physiological effects of caloric restriction (the delay in cancer mortality, for example), perhaps in humans.”
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.
A tremendous breakthrough occurred when scientists at the University of Wisconsin used high-density DNA microarrays (gene chips), a technology developed by Affymetrix (Santa Clara, California) to rapidly detect expression in up to 6,347 genes at one time. When researchers (Richard Weindruch and Tomas Prolla) compared gene activity in normally aging mice with gene expression in calorie-restricted mice, they found that many of the genetic changes of aging were reversible by calorie restriction (Lee et al. 1999).
Scientists at Biomarker Pharmaceuticals, a company funded (to date) exclusively by The Life Extension Foundation, dramatically advanced the model when (after studying 1200 genes) it was determined that the positive response of an animal to calorie restriction is much quicker than once theorized. It was previously thought that calorie restriction would have to be applied over the lifetime of the animal to be of significant advantage. Instead, it was determined that 70% of the changes in gene expression (caused by over a two-year calorie restricted regimen) occurred in only two to four weeks after placing mice on a calorie restricted diet. As Biomarker scientists established that even "senior" rodents realized about a 40% extension of life span when undergoing a calorie-restricted diet, rodents of all ages became candidates for life extension through caloric restriction.
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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Aging causes damage to proteins such as carbonylation (protein oxidation) and glycation (protein-sugar cross-linking). Mitochondrial energy diminishes and a cascade of events ensues causing increases in cytokines such as tumor necrosis factor alpha (TNF-a), interleukin-1B (IL-1B), and interleukin-6 (IL-6). In addition, aging can cause elevated levels of blood glucose, resulting in events associated with less well-being.
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