Effect Of Caloric Restriction On The Proliferation Of Skeletal Muscle Satellite Cells In Aged Mice And Its Mechanism

Objective To explore the effect of calorie restriction on the proliferation of satellite cell in aged rat skeletal muscles and its mechanism.Methods C57 BL mice were divided into three groups according to age: neonatal mice(less than 1 week),adult mice(3-4 months)and aged mice(15-16 months).The muscle satellite cell were sorted by fluorescence-activated cell sorting from limb muscles after digesting,and cell-cycle were analyzed.Western blot were used to assess Cyclin A,Cyclin E,Cyclin D1 expression of lamb muscles.12 of male elder mice were randomly divided into the old calorie restriction group(60% food of the control group)and the old ad libitum group.Fifteen weeks later,skeletal muscle index was obtained and the muscle satellite cell were sorted by fluorescence-activated cell sorting from limb muscles after digesting,and cell-cycle were analyzed.Western blot were used to assess Cyclin A,Cyclin E,Cyclin D1,AMPKα,p-AMPKα,SIRT1 expression of lamb muscles.Results Compare with the adult mice group(G0/G1 Phase 78.25±0.38;S+G2/M Phase 19.99±1.50),the satellite cell in neonatal mice group decreased in the percentage of G0/G1 Phase(58.89±0.43)(P<0.01),and increased(37.53±0.06)in the percentage of S+G2/M Phase(P<0.01);the satellite cell in aged mice group increased in the percentage of G0/G1 Phase(89.78±0.37)(P<0.01),and decreased in the percentage of S+G2/M Phase(10.40±0.70)(P<0.01).The Skeletal muscle index of anterior tibial muscle,gastrocnemius muscle and extensor digitorum longus between the two groups did not have significant differences(P>0.05).Compare with the adult group,the ratio of p-AMPKα/AMPKα(P<0.01)and the expression of SIRT1(P<0.01)in the old group decreased.The satellite cell in old calorie restriction group mice decreased(62.18±0.42)in the percentage of G0/G1 Phase compared with the old AL group(G0/G1 Phase 89.78±0.37;S Phase 4.29±1.57)(P<0.001),and increased(28.75±0.30)in the percentage of S Phase(P<0.001);the ratio of p-AMPKα/AMPKα(P<0.01)and the expression of Cyclin A(P<0.001),Cyclin E(P<0.01),SIRT1(P<0.01)in calorie restriction group mice increased compared with the old AL group,and the expression of Cyclin D1(P<0.01)reduced.Conclusion Caloric restriction can delay the proliferation degradation of skeletal muscle satellite cells in aging mice,which may related to the change of AMPK/SIRT signal pathway.