Present address: INRA – UMR 866 Differenciation Cellulaire et Croissance, Bât 22–2 place Pierre Viala, 34060 Montpellier Cedex 1, France.
Mitochondrial function and apoptotic susceptibility in aging skeletal muscle
Article first published online: 11 OCT 2007
© 2007 The Authors
Volume 7, Issue 1, pages 2–12, February 2008
How to Cite
Chabi, B., Ljubicic, V., Menzies, K. J., Huang, J. H., Saleem, A. and Hood, D. A. (2008), Mitochondrial function and apoptotic susceptibility in aging skeletal muscle. Aging Cell, 7: 2–12. doi: 10.1111/j.1474-9726.2007.00347.x
- Issue published online: 11 OCT 2007
- Article first published online: 11 OCT 2007
- Accepted for publication 21 September 2007
- contractile activity;
- mitochondrial biogenesis;
- oxidative stress;
- permeability transition pore;
- subsarcolemmal and intermyofibrillar mitochondria
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.