The impact of aging on mitochondrial proton leaks in human skeletal muscle (1159.9)

Abstract

Proton leaks are thought to account for 20‐25% of mitochondrial oxygen consumption. It has been postulated that mitochondrial proton cycling in senescent tissue may reduce free radical production. Here, we determined mitochondrial respiratory control in skeletal muscle biopsies obtained from young and older individuals. 6 young (31±3 yrs) and 10 older (58±7 yrs) subjects participated in this study. Mitochondrial respiration was determined in permeabilized myofibers after the addition of substrates, ADP and oligomycin. Thereafter, coupling control ratios were calculated. Coupled mitochondrial respiration tended to be higher in muscle from young vs. older subjects (38.0±3.1 vs. 31.7±2.8 pmol/mg/sec, P=0.16). ADP sensitivity was similar between groups, whereas oligomycin sensitivity was significantly lower in the older vs. young group (P<0.05). Mitochondrial ADP sensitivity is preserved in skeletal muscle of older individuals. However, mitochondria of older individuals are less sensitive to the ATP synthase inhibitor oligomycin. These data suggest that inner membrane proton conductance is elevated in skeletal muscle mitochondria with aging.Grant Funding Source: Supported by NIH (1R01 AG033761, P30 AG024832, 1 U54RR026141) and NIDRR (H133P110012) grants.