title: Caloric restriction and the aging process: a critique.
abstract: The main objective of this review is to provide an appraisal of the current status of the relationship between energy intake and the life span of animals. The concept that a reduction in food intake, or caloric restriction (CR), retards the aging process, delays the age-associated decline in physiological fitness, and extends the life span of organisms of diverse phylogenetic groups is one of the leading paradigms in gerontology. However, emerging evidence disputes some of the primary tenets of this conception. One disparity is that the CR-related increase in longevity is not universal and may not even be shared among different strains of the same species. A further misgiving is that the control animals, fed ad libitum (AL), become overweight and prone to early onset of diseases and death, and thus may not be the ideal control animals for studies concerned with comparisons of longevity. Reexamination of body weight and longevity data from a study involving over 60,000 mice and rats, conducted by a National Institute on Aging-sponsored project, suggests that CR-related increase in life span of specific genotypes is directly related to the gain in body weight under the AL feeding regimen. Additionally, CR in mammals and "dietary restriction" in organisms such as Drosophila are dissimilar phenomena, albeit they are often presented to be the very same. The latter involves a reduction in yeast rather than caloric intake, which is inconsistent with the notion of a common, conserved mechanism of CR action in different species. Although specific mechanisms by which CR affects longevity are not well understood, existing evidence supports the view that CR increases the life span of those particular genotypes that develop energy imbalance owing to AL feeding. In such groups, CR lowers body temperature, rate of metabolism, and oxidant production and retards the age-related pro-oxidizing shift in the redox state.
authors.affiliation: Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90089, USA. Electronic address: sohal@usc.edu.
authors.forename: Rajindar S
authors.initials: RS
authors.lastname: Sohal
authors.affiliation: Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Forster
mesh_terms: D000375:Aging; D000818:Animals; D001831:Body Temperature; D001835:Body Weight / Q000502:physiology*; D031204:Caloric Restriction; D004435:Eating; D002149:Energy Intake / Q000502:physiology; D004734:Energy Metabolism; D008017:Life Expectancy; D008136:Longevity; D051379:Mice; D016877:Oxidants / Q000096:biosynthesis; D051381:Rats
chemical_list: D016877:Oxidants
keywords: Aging; Caloric restriction; Dietary restriction; Energy restriction; Free radicals; Life span; Mechanisms of aging; Oxidative stress; Redox state; Redox stress hypothesis of aging