Mitochondrial function and apoptotic susceptibility in aging skeletal muscle

• Published in: Aging cell Vol. 7; no. 1; pp. 2 - 12
• Main Authors: Chabi, Béatrice, Ljubicic, Vladimir, Menzies, Keir J., Huang, Julianna H., Saleem, Ayesha, Hood, David A.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-02-2008; Wiley Open Access
• Subjects: Aging; Animals; Apoptosis; Citrate (si)-Synthase - analysis; contractile activity; Cytochromes c - metabolism; Electron Transport Complex IV - metabolism; Endodeoxyribonucleases - metabolism; Human health and pathology; Kinetics; Life Sciences; Male; Membrane Potential, Mitochondrial; Mitochondria, Muscle - enzymology; Mitochondria, Muscle - physiology; mitochondrial biogenesis; Mitochondrial Membrane Transport Proteins - metabolism; Mitochondrial Proteins - metabolism; Muscle, Skeletal - cytology; Muscle, Skeletal - enzymology; Muscle, Skeletal - physiology; Myofibrils - physiology; oxidative stress; Oxygen Consumption; permeability transition pore; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Rats; Rats, Inbred F344; Reactive Oxygen Species - metabolism; RNA-Binding Proteins - metabolism; Sarcolemma - physiology; sarcopenia; subsarcolemmal and intermyofibrillar mitochondria; Tissues and Organs; Transcription Factors - metabolism; permeability transition pore; contractile activity; subsarcolemmal and intermyofibrillar mitochondria; mitochondrial biogenesis; oxidative stress; sarcopenia
• ISSN: 1474-9718; 1474-9726; 1474-9728
• DOI: 10.1111/j.1474-9726.2007.00347.x

Summary
During aging, skeletal muscle undergoes sarcopenia, a condition characterized by a loss of muscle cell mass and alterations in contractile function. The origin of these decrements is unknown, but evidence suggests that they can be partly attributed to mitochondrial dysfunction. To characterize the nature of this dysfunction, we investigated skeletal muscle contractile properties, subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondrial biogenesis and function, as well as apoptotic susceptibility in young (6 months old) and senescent (36 months old) Fischer 344 Brown Norway rats. Muscle mass and maximal force production were significantly lower in the 36‐month group, which is indicative of a sarcopenic phenotype. Furthermore, contractile activity in situ revealed greater fatigability in the 36‐month compared to the 6‐month animals. This decrement could be partially accounted for by a 30% lower mitochondrial content in fast‐twitch muscle from 36‐month animals, as well as lower protein levels of the transcriptional coactivator peroxisome proliferator‐activated receptor γ coactivator‐1α. Enzyme activities and glutamate‐induced oxygen consumption rates in isolated SS and IMF mitochondria were similar between age groups. However, mitochondrial reactive oxygen species (ROS) production during state 3 respiration was ~1.7‐fold greater in mitochondria isolated from 36‐month compared to 6‐month animals, and was accompanied by a 1.8‐fold increase in the DNA repair enzyme 8‐oxoguanine glycosylase 1 in fast‐twitch muscle. Basal rates of release of cytochrome c and endonuclease G in SS mitochondria were 3.5‐ to 7‐fold higher from senescent animals. These data suggest that the age‐related sarcopenia and muscle fatigability are associated with enhanced ROS production, increased mitochondrial apoptotic susceptibility and reduced transcriptional drive for mitochondrial biogenesis.