Mitochondrial energetics is impaired in vivo in aged skeletal muscle

Aging Cell

Gilles Gouspillou²  Isabelle Bourdel-Marchasson²  Richard Rouland²  Guillaume Calmettes²  Marc Biran²  Véronique Deschodt-Arsac³  Sylvain Miraux²  Eric Thiaudiere²  Philippe Pasdois³  Dominique Detaille³  Jean-Michel Franconi²  Marion Babot¹  Véronique Trézéguet¹  Laurent Arsac² 

[1] Laboratoire de Physiologie Moléculaire et Cellulaire, Institut de Biochimie et Génétique Cellulaires, UMR 5095, CNRS-Université Bordeaux 2, Bordeaux Cedex, France;Résonance Magnétique des Systèmes Biologiques, UMR 5536 CNRS - Bordeaux Segalen University, Bordeaux, France;INSERM U1045 – Cardio-Thoracic Research Centre – and Rhythmology and Heart Modeling Institute (LIRYC), Bordeaux University, Bordeaux, France

关键词: adenosine nucleotide translocator;    affinity for ADP;    energetics;    in vivo;    mitochondria;    skeletal muscle aging;   

DOI  :  10.1111/acel.12147

来源: Wiley

【 摘 要 】

Summary

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 ³¹P 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.

【 授权许可】

Unknown   
© 2013 the Anatomical Society and John Wiley & Sons Ltd