Global Food Restriction

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Abstract

The use of restricted feeding paradigms to understand mechanisms of aging in rodent models is discussed. The phrase global food restriction is defined so as to avoid ambiguities that have arisen with the use of the phrase dietary restriction. Evidence is evaluated regarding the claim that such procedures not only extend longevity but also retard aging processes. Several hypotheses that have been advanced to explain this action (such as growth retardation, reduction of body fat, decreased metabolic rate, decreased plasma levels of various metabolites, and decreased levels of oxidative damage) are assessed and found wanting. Evidence is described in support of an overall mechanism in which hormesis plays an important role. It is suggested that moderate reduction of energy intake constitutes a low-intensity stressor that results in the mobilization of cellular defense mechanisms. These defense mechanisms decrease the accumulation of the cellular molecular damage that underlies senescence. It seems likely that the energy-restricted animal now exists in a new metabolic state in which many, rather than few, metabolic characteristics are altered. Many or all of these altered metabolic characteristics may play a role in the beneficial effects of caloric restriction.