Effects of caloric restriction on skeletal muscle mitochondrial proton leak in aging rats.

Long-term caloric restriction (CR) retards aging processes and increases maximum life span. We investigated the influence of CR on mitochondrial proton leaks in rat skeletal muscle. Because CR lowers oxidative damage to mitochondrial membrane lipids and proteins, we hypothesized that leak would be lower in mitochondria from old CR rats than in age-matched controls. Three groups (n = 12) were studied: 4-month-old "young" control rats (body weight: 404 g +/- 7 SEM), 33-month-old CR rats (body weight: 262 g +/- 3), and 33-month-old control rats (body weight: 446 g +/- 5). CR rats received 67% of the energy intake of old control rats, with adequate intakes of all essential nutrients. Maximum leak-dependent O2 consumption (State 4) was 23% lower in CR rats than in age-matched controls, whereas protonmotive force values were similar, supporting our hypothesis. The overall kinetics of leak were similar between the two groups of old rats; in the young, kinetics indicated higher protonmotive force values. The latter indication is consistent with aging-induced alterations in proton leak kinetics that are independent of dietary intervention. There was no influence of age or diet on serum T4 level, whereas T3 was lower in young than in old control rats. These results support and extend the oxidative stress hypothesis of aging.