The free radical hypothesis of aging: an appraisal of the current status.

The objective of this review article is to assess the current status of the predictions of the free radical hypothesis of aging, highlighting some of the controversies surrounding the previous assumptions. Topics for discussion include: metabolic rate and aging, oxidative stress and molecular damage during aging, antioxidants and aging, antioxidant defenses and life spans of different species, and pro-oxidant generation and aging. On the basis of currently available evidence, it is concluded that the free radical hypothesis has neither been proven nor disproven. Some of the earlier assumptions such as that antioxidant intake increases life span, or antioxidant defenses decline with age, or antioxidant defenses are positively correlated with life spans of different species, or that longer life spans are associated with lower autoxidizability, are not clearly supportable. Similarly, the assumption that oxygen free radicals govern the rate of aging via the infliction of molecular damage lacks compelling support. Enough information to lift the free radical hypothesis above the level of speculation has not yet been amassed. Clearly, further studies, some of which specifically focus on disproving this hypothesis, are needed to confirm its veracity.