Molecular basis for an attenuated mitochondrial adaptive plasticity in aged skeletal muscle.
Our intent was to investigate the mechanisms driving the adaptive potential of subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria in young (6 mo) and senescent (36 mo) animals in response to a potent stimulus for organelle biogenesis. We employed chronic electrical stimulation (10 Hz, 3 h/day, 7 days) to induce contractile activity of skeletal muscle in 6 and 36 mo F344XBN rats. Subsequent to chronic activity, acute stimulation (1 Hz, 5 min) in situ revealed greater fatigue resistance in both age groups. However, the improvement in endurance was significantly greater in the young, compared to the old animals. Chronic muscle use also augmented SS and IMF mitochondrial volume to a greater extent in young muscle. The molecular basis for the diminished organelle expansion in aged muscle was due, in part, to the collective attenuation of the chronic stimulation-evoked increase in regulatory proteins involved in mediating mitochondrial protein import and biogenesis. Furthermore, adaptations in mitochondrial function were also blunted in old animals. However, chronic contractile activity evoked greater reductions in mitochondrially-mediated proapoptotic signaling in aged muscle. Thus, mitochondrial plasticity is retained in aged animals, however the magnitude of the changes are less compared to young animals due to attenuated molecular processes regulating organelle biogenesis.
School of Kinesiology and Health Science, York University, Toronto, Ontario, M3J 1P3, Canada.
Vladimir
V
Ljubicic
Anna-Maria
AM
Joseph
Peter J
PJ
Adhihetty
Julianna H
JH
Huang
Ayesha
A
Saleem
Giulia
G
Uguccioni
David A
DA
Hood
D000223:Adaptation, Psychological / Q000502:physiology*; D000375:Aging / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D053938:DNA Fragmentation; D004558:Electric Stimulation; D003576:Electron Transport Complex IV / Q000378:metabolism; D008297:Male; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D053142:Mitochondrial Size / Q000502:physiology; D009119:Muscle Contraction / Q000502:physiology; D018763:Muscle Fatigue / Q000502:physiology; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000033:anatomy & histology / Q000502:physiology*; D009954:Ornithine Carbamoyltransferase / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D017382:Reactive Oxygen Species / Q000378:metabolism; D019802:Succinic Acid / Q000378:metabolism / Q000494:pharmacology
D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; D009124:Muscle Proteins; D017382:Reactive Oxygen Species; D019802:Succinic Acid; D003576:Electron Transport Complex IV; D009954:Ornithine Carbamoyltransferase