The free radical theory of frailty: Mechanisms and opportunities for interventions to promote successful aging.

The free radical theory of ageing has provided a framework of research into ageing based on Harman's idea that ageing was caused by damage produced by free radicals. However, several experiments have cast doubts on the general validity of the theory. The postulation of the free radical theory of frailty came from two basic facts: first that radicals not only act as damaging molecules, but also as signals to control cell function and second that on many occasions oxidative damage does not correlate with chronological but rather with unsuccessful ageing. Frailty is a geriatric concept by which an older person shows a lack of the feeling of wellbeing, unintentional weight loss, a relatively low grip strength, lowering the speed of walking, and difficulties to stand. If left untreated, frailty progresses to disability. Many interventions that prevent oxidative damage to cells do not affect longevity but have a clear effect on the prevention of frailty and its transition to disability. Clinical trials have shown that exercise programmes do not promote longevity but delay the onset of frailty. Experiments and mechanisms to support this idea are described.