Lack of muscle recovery after immobilization in old rats does not result from a defect in normalization of the ubiquitin-proteasome and the caspase-dependent apoptotic pathways.
Immobilization periods increase with age because of decreased mobility and/or because of increased pathological episodes that require bed-rest. Then, sarcopaenia might be partially explained by an impaired recovery of skeletal muscle mass after a catabolic state due to an imbalance of muscle protein metabolism, apoptosis and cellular regeneration. Mechanisms involved during muscle recovery have been little studied and in elderly they remain almost unknown. We show, in rats, that a short immobilization period during ageing initiated muscle atrophy that was indeed not recovered after 40 days. Immobilization was associated with an activation of both the ubiquitin-proteasome and the mitochondria-associated apoptotic pathways and the inflammatory and redox processes, and a decrease of cellular regeneration. We show that the lack of muscle recovery during ageing is not due to a defect in proteolysis or apoptosis down-regulation. These observations lead us to hypothesize that muscle protein synthesis activation after immobilization was altered during ageing.
INRA, UMR 1019 Unité de Nutrition Humaine, 63122 Saint Genès Champanelle, France. hugues.magne@clermont.inra.fr
Hugues
H
Magne
Isabelle
I
Savary-Auzeloux
Emilie
E
Vazeille
Agnès
A
Claustre
Didier
D
Attaix
Listrat
L
Anne
Santé-Lhoutellier
SL
Véronique
Gatellier
G
Philippe
Dominique
D
Dardevet
Lydie
L
Combaret
D000375:Aging / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D001835:Body Weight / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism; D020169:Caspases / Q000378:metabolism*; D018932:Chemokine CCL2 / Q000378:metabolism; D004435:Eating / Q000502:physiology; D005978:Glutathione / Q000378:metabolism; D019417:Hindlimb Suspension / Q000009:adverse effects*; D007249:Inflammation / Q000378:metabolism; D008297:Male; D024101:Mitochondrial Proteins / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D009133:Muscular Atrophy / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D051787:Myogenic Regulatory Factor 5 / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D025821:Polyubiquitin / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D050050:Protein Carbonylation / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration / Q000502:physiology*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; C489013:DIABLO protein, rat; D024101:Mitochondrial Proteins; D009124:Muscle Proteins; D051787:Myogenic Regulatory Factor 5; D017392:Thiobarbituric Acid Reactive Substances; D051636:X-Linked Inhibitor of Apoptosis Protein; D025821:Polyubiquitin; D020169:Caspases; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; D005978:Glutathione