Monday, February 11, 2008

Aging is slowed by calorie or protein restriction

In rodents a calorie restricted diet, significantly increases lifespan, decreases reproduction, and markedly decreases cancer rates.

It has been suggested that Darwinian fitness in animals is increased by the delay of reproductive function during periods of low food availability and that the saved resources are invested in maintenance of the body until food resources are available for successful reproduction.

Protein restriction appears to have the same effects on rodents as calorie restriction, though it is less well-studied. An understanding of mechanisms for this marked effect on aging and cancer is becoming clearer and may in good part be due to reduced oxidative damage.

The suggestion that maintenance functions are enhanced in calorie-restricted rats thus resulting in less oxidative damage is supported by the findings of more efficient DNA repair, better coupled mitochondrial respiration and a delay in the age-dependent decline of antioxidant defenses.

The higher level of antioxidant defenses could also account for the enhanced immune response in restricted animals. We have recently shown that either calorie or protein restriction decreases the rate of accumulation of oxidized protein that accompanies aging in rats and preliminary results suggest a decrease in preneoplastic foci and oxidative lesions in DNA as well.

Thus, the overall effect of these enhanced maintenance activities appears to be a reduction in oxidative damage to DNA and protein, a decrease in DNA and protein lesions, and a decrease in somatic mutations. Markedly lower mitotic rates are observed in a variety of tissues in calorie restricted compared to ad libitum fed rodent, which may also contribute to the decrease in tumor incidence.

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*Dietary restriction activates the pituitary adrenocorticotropic axis resulting in a decrease in the release of reproductive and mitogenic hormones. Decreases in mitogenic hormones such as insulin, TSH, growth hormone, estrogen, and prolactin decrease the likelihood of hormone-induced cancers, as has been shown in various animal studies. This is consistent with suppression of mitogenic hormones and decreased proto-oncogene expression. The lowered incidence of mammary tumors observed in calorie-restricted rats has been attributed to reduced circulating levels of the mammotropic hormones estrogen and prolactin.

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