Aging: a shift from redox regulation to oxidative damage

Proteins, nucleic acids, and lipids can undergo various forms of oxidative modification. In numerous instances, these modifications result in irreversible loss of function. The age-dependent accumulation of oxidatively modified and dysfunctional macromolecules provides the basis for the free radical theory of aging. Pro-oxidants, however, are also capable of catalyzing fully reversible modifications to protein. It is increasingly apparent that these reactions participate in redox-dependent regulation of cell metabolism and response to stress. The adventitious use of free radical species adds complexity to the experimental and theoretical manner in which the free radical theory is to be tested and considered. Elucidation of mechanisms by which reversible oxidative processes are controlled, the components involved, and the metabolic consequences and how they are altered with age will provide new insight on the aging process and attempts to delay the inevitable.