Skeletal muscle proteolysis in aging.
OBJECTIVE
To understand age-related changes in proteolysis and apoptosis in skeletal muscle in relation to oxidative stress and mitochondrial alterations.


RESULTS
During aging, a progressive loss of muscle mass (sarcopenia) has been described in both human and rodents. Sarcopenia is attributable to an imbalance between protein synthesis and degradation or between apoptosis and regeneration processes or both. Major age-dependent alterations in muscle proteolysis are a lack of responsiveness of the ubiquitin-proteasome-dependent proteolytic pathway to anabolic and catabolic stimuli and alterations in the regulation of autophagy. In addition, increased oxidative stress leads to the accumulation of damaged proteins, which are not properly eliminated, aggregate, and in turn impair proteolytic activities. Finally, the mitochondria-associated apoptotic pathway may be activated. These age-induced changes may contribute to sarcopenia and decreased ability of old individuals to recover from stress.


CONCLUSIONS
Alterations in proteasome-dependent or lysosomal proteolysis, increased oxidative stress, mitochondrial dysfunction, and apoptosis presumably contribute to the development of sarcopenia.
Combaret
Lydie
L
INRA, Centre Clermont-Ferrand-Theix, UMR1019, Unité Nutrition Humaine, St. Genès Champanelle, France. combaret@clermont.inra.fr
Dardevet
Dominique
D
Béchet
Daniel
D
Taillandier
Daniel
D
Mosoni
Laurent
L
Attaix
Didier
D
D000368:Aged; D000375:Aging / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D008247:Lysosomes / Q000378:metabolism; D053858:Metabolic Networks and Pathways; D008928:Mitochondria / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009133:Muscular Atrophy / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism
D009124:Muscle Proteins; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex; D002118:Calcium