ABSTRACT
Several lines of experimentation support the view that the genetic, biochemical, and bioenergetic functions of somatic mitochondria deteriorate during normal aging. Deletion mutations of the mitochondrial genome accumulate exponen tially with age in nerve and muscle tissue of humans and several other species. In muscle, a tissue that undergoes age-related atrophy in humans, there is an exponential rise in the number of cytochrome-oxidase-deficient fibers which is first detectable in the fourth decile of age. Most biochemical studies of animal mitochondrial activity indicate a decline in electron transport activity with age, as well as decreased bioenergetic capacity with age, as measured by mito chondrial membrane potential. Mitochondrial mutations may be both the result of mitochondrial oxidative stress and cells bearing pure populations of pathogenic mitochondrial mutations are sensitized to oxidant stress. Oxidant stress to mito chondria is known to induce the mitochondrial permeability transition, which has recently been implicated in the release o f cytochrome c and the initiation of apoptosis. Thus several lines of evidence support a contribution of mitochondrial dysfunction to the phenotypic changes associated with aging.
