Caloric restriction-induced life extension of rats and mice: a critique of proposed mechanisms.

In 1935, Clive McCay and colleagues reported that decreasing the food intake of rats extends their life. This finding has been confirmed many times using rat and mouse models. The responsible dietary factor in rats is the reduced intake of energy; thus, this phenomenon is frequently referred to as caloric restriction.

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.

The role of hormesis in life extension by dietary restriction.

The level of food restriction that results in life extension and retarded aging in rodents also enhances their ability to cope with intense stressors. Moreover, this level of dietary restriction (DR) leads to a modest increase in the daily peak concentration of plasma free corticosterone, which strongly points to DR as a low-intensity stressor. These findings suggest that hormesis plays a role in the life-extending and anti-aging actions of DR.