Mitochondrial respiratory capacity and coupling control decline with age in human skeletal muscle

• Published in: American journal of physiology: endocrinology and metabolism Vol. 309; no. 3; pp. E224 - E232
• Main Authors: Porter, Craig, Hurren, Nicholas M., Cotter, Matthew V., Bhattarai, Nisha, Reidy, Paul T., Dillon, Edgar L., Durham, William J., Tuvdendorj, Demidmaa, Sheffield-Moore, Melinda, Volpi, Elena, Sidossis, Labros S., Rasmussen, Blake B., Børsheim, Elisabet
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.08.2015
• Series: Endocrine and Metabolic Dysfunction during Aging and Senescence
• Subjects: Adenosine triphosphatase; Adult; Age differences; Aged; Aged, 80 and over; Aging; ATP; Biopsy; Call for Papers; Carbonyl Cyanide m-Chlorophenyl Hydrazone - pharmacology; Cohort Studies; Down-Regulation - drug effects; Electron Transport Complex I - antagonists & inhibitors; Electron Transport Complex I - metabolism; Electron Transport Complex II - antagonists & inhibitors; Electron Transport Complex II - metabolism; Female; Humans; Male; Middle Aged; Mitochondria; Mitochondria, Muscle - drug effects; Mitochondria, Muscle - enzymology; Mitochondria, Muscle - metabolism; Muscle, Skeletal - drug effects; Muscle, Skeletal - growth & development; Muscle, Skeletal - metabolism; Musculoskeletal system; Myofibrils - drug effects; Myofibrils - enzymology; Myofibrils - metabolism; Older people; Oligomycins - pharmacology; Oxidative Phosphorylation - drug effects; Phosphorylation; Physiology; Proton Ionophores - pharmacology; Quadriceps Muscle - drug effects; Quadriceps Muscle - growth & development; Quadriceps Muscle - metabolism; Respiration; Respiratory function; Uncoupling Agents - pharmacology; Young Adult
• ISSN: 0193-1849; 1522-1555; 1522-1555
• DOI: 10.1152/ajpendo.00125.2015

Mitochondrial health is critical to physiological function, particularly in tissues with high ATP turnover, such as striated muscle. It has been postulated that derangements in skeletal muscle mitochondrial function contribute to impaired physical function in older adults. Here, we determined mitochondrial respiratory capacity and coupling control in skeletal muscle biopsies obtained from young and older adults. Twenty-four young (28 ± 7 yr) and thirty-one older (62 ± 8 yr) adults were studied. Mitochondrial respiration was determined in permeabilized myofibers from the vastus lateralis after the addition of substrates oligomycin and CCCP. Thereafter, mitochondrial coupling control was calculated. Maximal coupled respiration (respiration linked to ATP production) was lower in muscle from older vs. young subjects ( P < 0.01), as was maximal uncoupled respiration ( P = 0.06). Coupling control in response to the ATP synthase inhibitor oligomycin was lower in older adults ( P < 0.05), as was the mitochondria flux control ratio, coupled respiration normalized to maximal uncoupled respiration ( P < 0.05). Calculation of respiratory function revealed lower respiration linked to ATP production ( P < 0.001) and greater reserve respiration ( P < 0.01); i.e., respiratory capacity not used for phosphorylation in muscle from older adults. We conclude that skeletal muscle mitochondrial respiratory capacity and coupling control decline with age. Lower respiratory capacity and coupling efficiency result in a reduced capacity for ATP production in skeletal muscle of older adults.