Prevention And Treatment Of Sarcopenia During Exercise Intervention Through Regulating Protein Degradation Pathway

Objective:In the present study,we constructed the model of sarcopenia using natural feeding of SD rats until 21 month of ages to evaluate the effect of two moderate-intensity exercise modes including voluntary wheeling running and ladder climbing during 8-week exercise period on the alleviation of sarcopenia via the regulation of protein degradation pathway.The aim of this study is to provide a theoretical basis and1 intervention guidance on the prevention and rehabilitation of sarcopenia.Methods: Totally 19 male rats were involved in a 21-month-feeding program to establish an animal model of sacopenia.The aged rats were randomly divided into three groups including senior control group(SC,n = 6),senior voluntary wheel running group(SW,n = 6),and senior ladder-climbing group(SL,n = 7),as well as 3-month old rats as the youth control group(YC,n = 10).After 8 weeks exercise intervention,the body weights of rats were determined,and blood and gastrocnemius samples were collected within 24 hours.The degree of muscular atrophy was evaluated by the ratio of gastrocnemius muscle weight to body weight.Antioxidant capacity was measured by the detection of serum SOD and MDA levels.The apoptosis rates in gastrocnemius tissues were measured by TUNEL assay.The expression of proteins related to energy metabolism,protein degradation and protein synthesis signaling pathways were detected by Western Blot assay.Results:1)The gastrocnemius weight of the rats from SC group was significantly lower than that of YC group(p < 0.001);while the gastrocnemius weights of SW and SL groups were significantly higher than that of SC group(p < 0.05).2)The serum SOD level of the rats from SC group was significantly lower(p < 0.001),while the content of MDA was significantly higher than that from YC group(p < 0.01).After exercise intervention,the serum SOD level of the rats from SW group was significantly increased(p < 0.05),while the serum SOD level of the rats from SL group showed an upward trend when compared with SC group.The serum MDA content of the rats from both SW and SL groups were decreased significantly.3)The gastrocnemius muscle fibers from SC group exhibited noticeable muscle atrophy and the phenomenon of central-nucleated myofibres when compared with those from YC group.After exercise intervention,the atrophy was improved obviously.Similarly,both SW and SL groups could reduce the damage on muscle fibers after exercise intervention,while the morphology of muscle fibers from SL group was significantly better than that from SC group.4)The apoptotic rate of gastrocnemius muscle in SC group was significantly higher than that in YC group(p < 0.001).After exercise intervention,the apoptotic rate was significantly decreased(p < 0.01).5)The expression of energy metabolism-related proteins such as AMPK,Sirt1 and PGC-1? was decreased significantly(p < 0.01)in SC group.After exercise intervention,the expression of these proteins in SL and SW groups was improved significantly(p < 0.01).6)Through the detection of protein degradation pathway in gastrocnemius muscle from each group,we found that the level of autophagy in SC group was significantly decreased,while the expression of proteins-related to ubiquitin protease was increased significantly.After exercise intervention,the autophagic signal pathway was activated and the expression of ubiquitin-related proteins was decreased.Conclusion:1.Aging process is accompanied by the loss of muscle mass.The exercise intervention at moderate intensity can play a certain role in the rehabilitation of sarcopenia.2.Aged rat displayed more serious skeletal muscle atrophy with a nuclear migration phenomenon.3.The level of antioxidant enzymes was decreased,while the oxidative damage was increased in aged rats.After exercise intervention,the antioxidant capacity can be improved significantly.4.The apoptosis rate of skeletal muscle cells in aged rats was increased,and exercise intervention could reduce the excessive myocyte apoptosis significantly in aged rats.5.Exercise intervention could enhance energy metabolism,autophagic signal and protein synthesis of skeletal muscle,and reduce protein degradation regulated by ubiquitin proteasome.In summary,exercise intervention could improve the imbalance on protein metabolism in sarcopenia,and regulate protein degradation pathways including ubiquitin proteasome and autophagy pathway.In this study,both exercise intervention modes at moderate intensity could alleviate or rescue the muscle atrophy in aged rats,which will provide a economical therapy for sarcopenia.