Age-Associated Impairments in Mitochondrial ADP Sensitivity Contribute to Redox Stress in Senescent Human Skeletal Muscle

Abstract

It remains unknown if mitochondrial bioenergetics are altered with aging in humans. We established an in vitro method to simultaneously determine mitochondrial respiration and H₂O₂ emission in skeletal muscle tissue across a range of biologically relevant ADP concentrations. Using this approach, we provide evidence that, although the capacity for mitochondrial H₂O₂ emission is not increased with aging, mitochondrial ADP sensitivity is impaired. This resulted in an increase in mitochondrial H₂O₂ and the fraction of electron leak to H₂O₂, in the presence of virtually all ADP concentrations examined. Moreover, although prolonged resistance training in older individuals increased muscle mass, strength, and maximal mitochondrial respiration, exercise training did not alter H₂O₂ emission rates in the presence of ADP, the fraction of electron leak to H₂O₂, or the redox state of the muscle. These data establish that a reduction in mitochondrial ADP sensitivity increases mitochondrial H₂O₂ emission and contributes to age-associated redox stress.

Keywords: ADP; H(2)O(2); ROS; aging; bioenergetics; exercise; mitochondria; muscle; resistance training; respiration.