CALORIC RESTRICTION AS A MECHANISM MEDIATING RESISTANCE TO ENVIRONMENTAL DISEASE

It has been observed that susceptibility to many degenerative diseases increases concurrently with industrialization and rising living stand ards. Although epidemiologic studies suggest that specific environment al and dietary factors may be important, caloric intake alone (as refl ected in body size) may account for much of the differential risk obse rved among diverse human populations. it has been suggested from anima l studies that caloric intake may be the primary effector for many hor monal, metabolic, physiologic, and behavioral responses that coordinat e reproductive strategy to apparent availability of food. When caloric intake is excessive, particularly at critical developmental stages, p hysiologic priorities are set for body growth and fecundity rather tha n for endurance and longevity. The converse occurs during periods of f amine, thus increasing the probability that sufficient individuals sur vive to restore the population when conditions improve. Calorically re stricted rodents have significantly longer reproductive and total life spans than their ad libitum-fed controls and exhibit a spectrum of bi ochemical and physiologic alterations that characterize their adaptati on to reduced caloric intake. These include reduced stature, hypercort icism in the absence of elevated adrenocorticotropic hormone levels, i ncreased metabolic efficiency, decreased mitogenic response coupled wi th increased rates of apoptosis, reduced inflammatory response, induct ion of stress proteins and DNA repair enzymes, altered drug-metabolizi ng enzyme expression, and modified cell-mediated immune function. The overall profile of these changes is one of improved defense against en vironmental stress. This has been suggested as the mechanistic basis f or the protective effects of low body weight on radiation-and chemical ly induced cancers in experimental animals. It may also explain the si gnificantly higher thresholds of acute toxicity observed when calorica lly restricted rodents are exposed to certain lest compounds.