GLUTATHIONE, OXIDATIVE STRESS AND AGING

The free radical theory of aging proposes that the impairment in physi ological performance associated with aging is caused by the detrimenta l effects of oxygen free radicals. This is interesting because it prov ides us with a theoretical framework to understand aging and because i t suggests a rationale for intervention, i.e., antioxidant administrat ion, Thus, the study of antioxidant systems of the cell may be very im portant in gerontological studies. Glutathione is one of the main nonp rotein antioxidants in the cell which, together with its related enzym es, constitute the ''glutathione system.'' The involvement of glutathi one in aging has been known since the early seventies. Several studies have reported that reduced glutathione is decreased in cells from old animals, whereas oxidized glutathione tends to be increased. Recent e xperiments from our laboratory have underscored the importance of cell ular compartmentation of glutathione. Mitochondrial glutathione plays a key role in the protection against free radical damage associated wi th aging. Oxidative damage to mitochondrial DNA is directly related to an oxidation of mitochondrial glutathione. In fact, aging is associat ed with oxidative damage to proteins, nucleic acids, and lipids. These molecular lesions may be responsible for the low physiological perfor mance of aged cells. Thus, antioxidant supplementation may be a ration al way to partially protect against age-associated impairment in perfo rmance. Apoptosis, a programmed cell death, is an area of research whi ch has seen an explosive growth. Glutathione is involved in apoptosis: apoptotic cells have lower levels of reduced glutathione, and adminis tration of glutathione precursors prevent, or at least delay, apoptosi s. Age-associated diseases constitute a major concern for researchers involved in aging. Free. radicals are involved in many such diseases; for instance, cancer, diabetes or atherosclerosis. The key role of glu tathione and other antioxidants in the pathophysiology of aging and ag e-associated diseases is discussed in this review.