Dietary restriction and aging: historical phases, mechanisms and current directions.

Energy intake restriction (ER) without essential nutrient deficiency retards aging and extends life span in all species tested so far, and across wide phylogenetic differences. Historical phases of this model system for studying aging have included modulation of the survival curve, effects on disease susceptibility and effects on physiological indices of aging; the current phase focuses upon possible mechanisms whereby ER influences such widely diverse phenomena. Mechanistic possibilities include effects on the immune system, on basal state and proliferation potential, metabolic rate, DNA repair, levels of free radical scavengers, chromatin structure and protein synthesis and turnover. The ER model may also be useful in analyzing unifactorial versus multifactorial theories of aging, and in clarifying the possible significance of physiological markers that correlate with differences in maximum life spans between species.