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RESEARCH PRODUCT

FREE RADICAL THEORY OF FRAILTY: MOLECULAR MECHANISMS OF FRAILTY RESULTING FROM OXIDATIVE STRESS

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description

The free radical theory of ageing provided an intellectual framework for many laboratories working on ageing. However, experimental and clinical evidence showing that high doses of antioxidants did not have an effect on ageing or on age-associated diseases, cast doubts on the validity of this theory. Data from our own laboratory showed that oxidative stress does not correlate with age, especially in the geriatric population, but rather with the frailty state. This has led us to postulate the free radical theory of frailty in which frailty is associated with oxidative stress, but age itself is not. Superoxide dismutase deficient mice are more frail than controls. But more importantly, we observed that animals overexpressing glucose-6-phosphate dehydrogenase that are protected against oxidative stress, delay frailty and are more vigorous than controls. We will describe experiments from both experimental animals and human cohorts that provide support to the free radical theory of frailty.