title: Alterations in intrinsic mitochondrial function with aging are fiber type-specific and do not explain differential atrophy between muscles.
abstract: To determine whether mitochondrial dysfunction is causally related to muscle atrophy with aging, we examined respiratory capacity, H(2) O(2)  emission, and function of the mitochondrial permeability transition pore (mPTP) in permeabilized myofibers prepared from four rat muscles that span a range of fiber type and degree of age-related atrophy. Muscle atrophy with aging was greatest in fast-twitch gastrocnemius (Gas) muscle (-38%), intermediate in both the fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus (Sol) muscles (-21%), and non-existent in adductor longus (AL) muscle (+47%). In contrast, indices of mitochondrial dysfunction did not correspond to this differential degree of atrophy. Specifically, despite higher protein expression for oxidative phosphorylation (oxphos) system in fast Gas and EDL, state III respiratory capacity per myofiber wet weight was unchanged with aging, whereas the slow Sol showed proportional decreases in oxphos protein, citrate synthase activity, and state III respiration. Free radical leak (H(2) O(2)  emission per O(2)  flux) under state III respiration was higher with aging in the fast Gas, whereas state II free radical leak was higher in the slow AL. Only the fast muscles had impaired mPTP function with aging, with lower mitochondrial calcium retention capacity in EDL and shorter time to mPTP opening in Gas and EDL. Collectively, our results underscore that the age-related changes in muscle mitochondrial function depend largely upon fiber type and are unrelated to the severity of muscle atrophy, suggesting that intrinsic changes in mitochondrial function are unlikely to be causally involved in aging muscle atrophy.
authors.affiliation: Department of Kinesiology, McGill University, Montreal, Quebec, Canada.
authors.forename: Martin
authors.initials: M
authors.lastname: Picard
authors.forename: Darmyn
authors.initials: D
authors.lastname: Ritchie
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Thomas
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Wright
authors.forename: Russell T
authors.initials: RT
authors.lastname: Hepple
mesh_terms: D000375:Aging; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002950:Citrate (si)-Synthase / Q000235:genetics / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D000083162:Mitochondrial Permeability Transition Pore; D009119:Muscle Contraction / Q000502:physiology; D018656:Muscle Fibers, Fast-Twitch / Q000378:metabolism* / Q000473:pathology; D018657:Muscle Fibers, Slow-Twitch / Q000378:metabolism* / Q000473:pathology; D009133:Muscular Atrophy / Q000378:metabolism* / Q000473:pathology; D009928:Organ Specificity; D010539:Permeability; D051381:Rats; D012503:Saponins / Q000737:chemistry
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D012503:Saponins; D006861:Hydrogen Peroxide; D003576:Electron Transport Complex IV; D002950:Citrate (si)-Synthase; D002118:Calcium