Oxidative stress, dietary restriction and aging

Abstract

It is accepted that dietary restriction (DR) feeding regimes will extend life span and even slow the rate of aging in a wide range of invertebrate and vertebrate species. In spite of significant research effort however, the biochemical mechanism underlying this effect still remains to be resolved. Although a body of data supports the interpretation that DR feeding regimes reduce the intensity of oxidative stress and damage in tissues of older animals, direct experimental confirmation is lacking that manipulating oxidative stress will modify the rate of aging. In tissues from rodent species the major cause of reduced exposure to reactive oxygen species (ROS) under DR feeding conditions results from a lower rate of ROS generation at the mitochondria. Recent work has suggested a plausible explanation of how DR feeding induces this adaptive response. What remains unclear is the cellular target in both fully fed and DR fed animals that is sensitive to ROS and thereby determines the rate of aging. Switching rodents between feeding regimes in mid-life or later provides little evidence of a memory effect of the initial feeding regime on ultimate life-time survival. This observation does not therefore support the interpretation that the extended survival induced by DR feeding results from a slower life time rate of accrual of oxidative damage. The use of a small molecular mimetic of the DR effect may provide an alternative experimental approach to identify the mechanism underlying the extended survival observed.