Role of hormesis in life extension by caloric restriction.

Caloric restriction (CR) markedly extends the life of rats, mice and several other species, and it also modulates age-associated physiological deterioration and delays the occurrence and/or slows progression of age-associated diseases. The level of CR that retards the aging processes is a low-intensity stressor, which enhances the ability of rats and mice of all ages to cope with intense stressors. CR thus exhibits a hormetic action in these species, and therefore it is hypothesized that hormesis plays a role in the life-extending and anti-aging actions of CR. Both the findings in support of this hypothesis and those opposing it are critically considered. However, it is likely that hormesis is not the only process contributing to CR-induced life extension. It is proposed that two general processes are involved in CR-induced life extension. One is the reduced endogenous generation of damaging agents, such as reactive oxygen species. The second is hormesis, which enhances processes that protect against the action of damaging agents and also promotes processes that repair the damage once it occurs.