Hyperthermia-Induced Mitochondrial Damage Is Exacerbated With Aging

Heat stress produces exaggerated oxidative damage with aging, and recent studies implicate mitochondria, a primary source of prooxidant production, as a key contributor to this response. In the current study, liver mitochondria isolated from either control or heat‐stressed young (6 mo) and old (24 mo) Fischer 344 rats (n=6/group) were assessed for structural and functional damage as well as endpoints indicative of oxidative stress. Electron microscopy revealed structural damage to mitochondria from both young and, to a greater extent, old heat stressed rats. Consistent with increased lipid peroxidation, 4‐hydroxynonenal‐modified protein was increased above control levels in mitochondria from both young and, again, to a greater extent in old rats exposed to hyperthermia. ATP and immunoreactive cytochrome c protein levels were significantly decreased in mitochondria from old but not young rats exposed to heat stress, suggesting that hyperthermia notably compromised mitochondrial function in aged animals. Taken together, the data indicate that, relative to young animals, mitochondria from aged rats are more vulnerable to oxidative damage caused by heat stress. These results support the speculation that mitochondrial damage and dysfunction could cause amplified prooxidant production that contributes to the increased susceptibility of aged organisms to physiological stressors. (NIH AG12350)