title: Autophagic response to exercise training in skeletal muscle with age.
abstract: Autophagy, a highly conserved quality control mechanism, is essential for the maintenance of cellular homeostasis and for the orchestration of an efficient cellular response to stress. During aging, the efficiency of autophagic degradation declines, and intracellular waste products accumulate. Therefore, in this study, we tested the hypothesis that skeletal muscle from old mice would have decreased autophagosome formation when compared to the muscle from young mice. We also examined whether autophagic regulatory events differ between muscle fiber types and in response to exercise in aged male mice. The extensor digitorum longus (EDL) and gastrocnemius muscles were studied in young and old ICR mice. Exercise was performed by allowing the mice to run on a treadmill with a 5° incline at 16.4 m/min for 40 min/day, 5 days/week for 8 weeks after a 1-week adaptation period. Our results indicated that the levels of microtubule-associated protein 1b light chain 3, a marker of autophagosome formation, were lower in both the EDL and the gastrocnemius muscle of old mice compared to those young mice. To identify the factors related to the changes observed, the expression of autophagy regulatory proteins was examined in the EDL and gastrocnemius muscles. Beclin-1, autophagy-related gene 7 (ATG7), and lysosome-associated membrane protein were found to be lower in the EDL and gastrocnemius muscles of old mice compared to those in the young mice, then Beclin-1, ATG7, and muscle-specific RING finger protein-1 upregulated after regular exercise. Moreover, the muscle weight/body weight was significantly increased only in the gastrocnemius muscle of the old trained mice. These data suggest that autophagy regulatory events are attenuated in old skeletal muscle. However, this effect is upregulated when animals are subjected to exercise training.
authors.affiliation: Institute of Biotechnology, Chungnam National University, Daejeon, Korea.
authors.forename: Yong An
authors.initials: YA
authors.lastname: Kim
authors.forename: Young Sang
authors.initials: YS
authors.lastname: Kim
authors.forename: Seung Lyul
authors.initials: SL
authors.lastname: Oh
authors.forename: Hee-Jae
authors.initials: HJ
authors.lastname: Kim
authors.forename: Wook
authors.initials: W
authors.lastname: Song
mesh_terms: D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001343:Autophagy / Q000235:genetics*; D000071193:Autophagy-Related Protein 7; D000071186:Beclin-1; D015415:Biomarkers / Q000378:metabolism; D001835:Body Weight; D015870:Gene Expression; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009929:Organ Size; D010805:Physical Conditioning, Animal / Q000502:physiology*; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C502661:Atg7 protein, mouse; D000071186:Beclin-1; C115010:Becn1 protein, mouse; D015415:Biomarkers; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D009124:Muscle Proteins; D000070584:Tripartite Motif Proteins; C499084:Trim63 protein, mouse; D044767:Ubiquitin-Protein Ligases; D000071193:Autophagy-Related Protein 7