Mitochondria in organismal aging and degeneration

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 exponentially with age in nerve and muscle tissue of humans and multiple other species. In muscle, a tissue that undergoes age-related fiber loss and 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 mitochondrial 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 mitochondria is known to induce the mitochondrial permeability transition, which has recently been implicated in the release of 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.

Changes in Mitochondrial Status Associated with Altered Ca2+Homeostasis in Aged Cerebellar Granule Neurons in Brain Slices

“…In the brain, the activity of the complex III of the respiratory chain, considered crucial for the activity of the entire oxidative phosphorylation system, was significantly decreased in old mice (Kwong and Sohal, 2000); measurements in hepatocytes showed a marked degree of age-related decline of the average mitochondrial membrane potential (Hagen et al, 1997). The observations presented here tell a similar story, but f uture experiments are required to determine whether the changes observed in aged neurons are attributable to mitochondrial DNA lesions/mutations (Cortopasi and Wong, 1999) or to other structural or f unctional changes .…”

“…Several lines of evidence suggest that mitochondria are affected by aging, becoming progressively more damaged in senescent tissue (Lenaz, 1998;Cortopasi and Wong, 1999). Aged mitochondria display a significant reduction in the activity of the various electron-transport complexes and an age-associated alteration in the mitochondrial membrane potential (Hagen et al, 1997;Kwong and Sohal, 2000).…”

Reduced Mitochondrial Adenosine Triphosphate Synthesis in Skeletal Muscle in Patients With Child–Pugh Class B and C Cirrhosis

“…At the same time it is well known that the concentration and size of mitochondria and activity of mitochondrial enzymes in skeletal muscle is reduced with aging and sedentary lifestyle. [59][60][61] These changes can, to some extent, be reversed with endurance training, and even light physical activity has a positive effect on mitochondrial enzyme activity. 61,62 Our patients and controls were well matched according to age but despite the fact that the controls were chosen by their sedentary lifestyle there may still be differences.…”

The impact of advancing donor age on histologic recurrence of hepatitis C infection: The perils of ignored maternal advice

“…There is good evidence that the genetic, biochemical, and bioenergetic functions of somatic mitochondria deteriorate during normal aging. 12,13 Mitochondrial mutations accumulate with aging, increasing susceptibility to oxidative stress, a hallmark of chronic HCV infection. Oxidative stress is known to induce mitochondrial permeability transition, a process recently implicated in the release of cytochrome c and the initiation of apoptosis.…”

“…Oxidative stress is known to induce mitochondrial permeability transition, a process recently implicated in the release of cytochrome c and the initiation of apoptosis. 12,13 Perhaps the most likely explanation is that the aging hepatocyte's clock is simply running out. Hepatocyte telomere length is shortened during each cell division, a process that limits the lifespan of primary human cells in vitro.…”