title: Mitochondrial functional impairment with aging is exaggerated in isolated mitochondria compared to permeabilized myofibers.
abstract: Mitochondria regulate cellular bioenergetics and apoptosis and have been implicated in aging. However, it remains unclear whether age-related loss of muscle mass, known as sarcopenia, is associated with abnormal mitochondrial function. Two technically different approaches have mainly been used to measure mitochondrial function: isolated mitochondria and permeabilized myofiber bundles, but the reliability of these measures in the context of sarcopenia has not been systematically assessed before. A key difference between these approaches is that contrary to isolated mitochondria, permeabilized bundles contain the totality of fiber mitochondria where normal mitochondrial morphology and intracellular interactions are preserved. Using the gastrocnemius muscle from young adult and senescent rats, we show marked effects of aging on three primary indices of mitochondrial function (respiration, H(2) O(2) emission, sensitivity of permeability transition pore to Ca(2+) ) when measured in isolated mitochondria, but to a much lesser degree when measured in permeabilized bundles. Our results clearly demonstrate that mitochondrial isolation procedures typically employed to study aged muscles expose functional impairments not seen in situ. We conclude that aging is associated with more modest changes in mitochondrial function in sarcopenic muscle than suggested previously from isolated organelle studies.
authors.affiliation: Department of Kinesiology, McGill University, Montreal, QC H2W 1S4, Canada.
authors.forename: Martin
authors.initials: M
authors.lastname: Picard
authors.forename: Darmyn
authors.initials: D
authors.lastname: Ritchie
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Wright
authors.forename: Caroline
authors.initials: C
authors.lastname: Romestaing
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Thomas
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Rowan
authors.forename: Tanja
authors.initials: T
authors.lastname: Taivassalo
authors.forename: Russell T
authors.initials: RT
authors.lastname: Hepple
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000502:physiology*; D008931:Mitochondria, Muscle / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D010539:Permeability; D051381:Rats; D011916:Rats, Inbred F344; D011919:Rats, Inbred Strains; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D002118:Calcium