title: Mitochondrial energetics is impaired in vivo in aged skeletal muscle.
abstract: With aging, most skeletal muscles undergo a progressive loss of mass and strength, a process termed sarcopenia. Aging-related defects in mitochondrial energetics have been proposed to be causally involved in sarcopenia. However, changes in muscle mitochondrial oxidative phosphorylation with aging remain a highly controversial issue, creating a pressing need for integrative approaches to determine whether mitochondrial bioenergetics are impaired in aged skeletal muscle. To address this issue, mitochondrial bioenergetics was first investigated in vivo in the gastrocnemius muscle of adult (6 months) and aged (21 months) male Wistar rats by combining a modular control analysis approach with (31) P magnetic resonance spectroscopy measurements of energetic metabolites. Using this innovative approach, we revealed that the in vivo responsiveness ('elasticity') of mitochondrial oxidative phosphorylation to contraction-induced increase in ATP demand is significantly reduced in aged skeletal muscle, a reduction especially pronounced under low contractile activities. In line with this in vivo aging-related defect in mitochondrial energetics, we found that the mitochondrial affinity for ADP is significantly decreased in mitochondria isolated from aged skeletal muscle. Collectively, the results of this study demonstrate that mitochondrial bioenergetics are effectively altered in vivo in aged skeletal muscle and provide a novel cellular basis for this phenomenon.
authors.affiliation: Résonance Magnétique des Systèmes Biologiques, UMR 5536 CNRS - Bordeaux Segalen University, Bordeaux, France; Département de Kinanthropologie, Université du Québec à Montréal, Montreal, Quebec, Canada.
authors.forename: Gilles
authors.initials: G
authors.lastname: Gouspillou
authors.forename: Isabelle
authors.initials: I
authors.lastname: Bourdel-Marchasson
authors.forename: Richard
authors.initials: R
authors.lastname: Rouland
authors.forename: Guillaume
authors.initials: G
authors.lastname: Calmettes
authors.forename: Marc
authors.initials: M
authors.lastname: Biran
authors.forename: Véronique
authors.initials: V
authors.lastname: Deschodt-Arsac
authors.forename: Sylvain
authors.initials: S
authors.lastname: Miraux
authors.forename: Eric
authors.initials: E
authors.lastname: Thiaudiere
authors.forename: Philippe
authors.initials: P
authors.lastname: Pasdois
authors.forename: Dominique
authors.initials: D
authors.lastname: Detaille
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Franconi
authors.forename: Marion
authors.initials: M
authors.lastname: Babot
authors.forename: Véronique
authors.initials: V
authors.lastname: Trézéguet
authors.forename: Laurent
authors.initials: L
authors.lastname: Arsac
authors.forename: Philippe
authors.initials: P
authors.lastname: Diolez
mesh_terms: D033741:Adenine Nucleotide Translocator 1 / Q000378:metabolism; D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000375:Aging / Q000378:metabolism*; D000818:Animals; D004734:Energy Metabolism; D006863:Hydrogen-Ion Concentration; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D009119:Muscle Contraction / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism*; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation; D010710:Phosphates / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D033741:Adenine Nucleotide Translocator 1; D010710:Phosphates; D010725:Phosphocreatine; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate
keywords: adenosine nucleotide translocator; affinity for ADP; energetics; in vivo; mitochondria; skeletal muscle aging
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