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

http://www.cell.com/cell-reports/abstract/S2211-1247(18)30264-X

Graham P. Holloway, Andrew M. Holwerda, Paula M. Miotto, Marlou L. Dirks, Lex B. Verdijk, and Luc J.C. van Loon

• The authors sought to determine whether there is an age-associated increase in mitochondrial reactive oxygen species (ROS) in vitro, using permeabilized muscle fibres.
• They find that the capacity of mitochondrial H2O2 emission does not increase with ageing
• However, ADP sensitivity does reduce with age. Consequently, H2O2 levels increase with age.
• Increasing muscle mass, strength, and maximal mitochondrial respiration through exercise in older individuals did not alter H2O2 emission rates, the fraction of electron leak to H2O2 or the redox state of muscle.
• In summary, reduction in mitochondrial ADP sensitivity increases mitochondrial H2O2 emission, which cannot be rescued through resistance training in later life (although there were other benefits to health of these individuals).