Resistance exercise activates skeletal muscle satellite cells in aged rats:role of adiponectin receptor 1 pathway

Pan Dong; Yang Jialing; Tian Wei; Wang Dongji; Zhu Zheng; Ma Wenchao; Liu Na; Fu Changxi

doi:10.12307/2026.061

Abstract：BACKGROUND:Muscle atrophy(sarcopenia)and muscle weakness caused by aging are becoming increasingly serious health problems,and there is currently a lack of effective drug treatments.Exercise training,especially resistance exercise,plays an important role in preventing muscle atrophy;however,its molecular mechanism is not yet fully understood. OBJECTIVE:To explore the effects of regular resistance exercise on skeletal muscle satellite cells in aging rats and the possible mechanism. METHODS:Forty-five 20-month-old male SD rats were randomly divided into old sedentary,old exercise,or old exercise inhibitor groups,and ten 6-month-old male SD rats were selected as young sedentary group.Rats in young sedentary and old sedentary groups were kept quietly in mouse cage,while those of old exercise group performed weight-bearing ladder training and old exercise inhibitor group was given administration with adiponectin receptor 1 inhibitor while exercising,in which the intervention period was lasting for 12 weeks.After the intervention,the endurance and strength levels were determined by grated treadmill exercise test and progressive tail-loaded ladder exercise test,respectively.The gastrocnemius was isolated,and the adiponectin content was detected by enzyme-linked immunosorbent assay.The cell cross-sectional area was measured by hematoxylin-eosin staining.The mitochondrial DNA copy number was examined by real-time fluorescence quantitative PCR.Cell proliferation was detected by proliferating cell nuclear antigen immunohistochemical staining.The number of activated skeletal muscle satellite cells was measured by paired box gene 7/myogenic differentiation antigen immunofluorescence staining.Immunoblotting was used to detect the expression of related proteins in skeletal muscle.Adiponectin receptor 1 agonist AdiopRon was co-incubated with satellite cells cultured in vitro for 24 hours.Paired box gene 7/myogenic differentiation antigen immunofluorescence staining was used to detect the number of activated satellite cells.Western blotting was used to detect the expression of AMP-activated protein kinase protein in satellite cells. RESULTS AND CONCLUSION:(1)Compared with old sedentary group,endurance and strength level,gastrocnemius mass index,adiponectin content,cell cross-sectional area,mitochondrial DNA copy number,cell proliferation by proliferating cell nuclear antigen+cell counts,and paired box gene 7+/myogenic differentiation antigen+cell counts were increased(P<0.05);total protein content and protein expression of adiponectin receptor 1,peroxisome proliferator-activated receptor γ coactivator 1-alpha,nuclear respiratory factor 1,mitochondrial transcription factor A,protein kinase B,mammalian target of rapamycin,P70 Ribosomal protein S6 kinase,paired box gene 7,myogenic differentiation antigen,myogenin,and myogenic factor 5 were upregulated(P<0.05)in the old exercise group.(2)The above benefits of exercise on aging skeletal muscle were diminished after administration with adiponectin receptor 1 inhibitor(P<0.05).(3)Cell culture experiments found that AdiopRon could increase the number of paired box gene 7+/myogenic differentiation antigen+cells and the expression of AMP-activated protein kinase protein in satellite cells.These findings indicate that regular resistance exercise activates satellite cells through adiponectin receptor 1 pathway,thereby promoting muscle cell proliferation and restoring skeletal muscle quality and function in aged rats.Adiponectin receptor 1 is a key target for regular exercise to protect against muscle mass loss and strength decline during aging.