Mitochondria in organismal aging and degeneration

Several lines of experimentation support the view that the genetic, biochem ical and bioenergetic functions of somatic mitochondria deteriorate during normal aging. Deletion mutations of the mitochondrial genome accumulate exp onentially with age in nerve and muscle tissue of humans and multiple other species. In muscle, a tissue that undergoes age-related fiber loss and atr ophy in humans, there is an exponential rise in the number of cytochrome-ox idase-deficient fibers, which is first detectable in the fourth decile of a ge. Most biochemical studies of animal mitochondrial activity indicate a de cline in electron transport activity with age, as well as decreased bioener getic capacity with age, as measured by mitochondrial membrane potential. M itochondrial mutations may be both the result of mitochondrial oxidative st ress, and cells bearing pure populations of pathogenic mitochondrial mutati ons are sensitized to oxidant stress. Oxidant stress to mitochondria is kno wn to induce the mitochondrial permeability transition, which has recently been implicated in the release of cytochrome c and the initiation of apopto sis. Thus several lines of evidence support a contribution of mitochondrial dysfunction to the phenotypic changes associated with aging. (C) 1999 Else vier Science B.V. All rights reserved.