Dietary restriction and aging.

The diet-restricted rodent model has been and is a major tool in experimental biogerontology. A spectrum of findings indicates that dietary restriction retards the aging processes of mice and rats, the most salient of which is the increase in mortality rate doubling time. It also maintains many physiological processes in a youthful state and, most strikingly, retards or prevents almost all age-associated disease processes. Current emphasis is on the mechanisms underlying the anti-aging actions of dietary restriction. The major effort for determining mechanism has focused on putative primary aging processes. A clue has emerged from the findings that it is the restriction of energy intake that is the dietary factor responsible for the anti-aging actions. However, reducing the metabolic rate is not involved. The challenge is to learn how the reduction of energy intake per animal (not per unit of body mass) is coupled to the retardation of aging processes. One of our working hypotheses is that dietary restriction alters nervous and/or endocrine functions that influence the characteristics (not the rate) of fuel use; this modulation in fuel-use characteristics is proposed to retard the aging processes. Our findings on carbohydrate metabolism are in accord with this view. Diet-restricted rats can use carbohydrate fuel as effectively as ad libitum fed rats while maintaining lower plasma glucose and insulin level. Maintenance of these low levels may protect against long-term damaging actions of these substances. Dietary restriction also protects against oxidative damage and, of course, oxidative damage is probably an inevitable component of fuel use.(ABSTRACT TRUNCATED AT 250 WORDS)