A Survey Of Body Composition In Elderly People And Study Of Trimetazidine Intervention

ObjectivePart 1:To analyze relationship between percentage body fat(PBF)and total muscle mass index(TMMI)and obesity which have association with muscle mass in elderly people.Part 2:To assess the efficacy and safety of trimetazidine(TMZ)in elderly patients with stable angina and poor muscle strength or physical performance.Part 3:To discuss the potential mechanism of TMZ in improving skeletal muscle functions by establishing senescent C2C12 myoblasts.MethodsPart 1:A cross-sectional study was carried out in Chinese PLA General Hospital with 3240 elderly participants who underwent a health check-up examination between February 2016 and February 2017.Linear Regression was used to examine relationship between PBF and TMMI.Logistic regression was used to analyze obesity which have relationship with low muscle mass(LMM).Part 2:Fifty-three eligible patients were randomly assigned to either 'TMZ' or 'control'from June to November 2018 in Chinese PLA General Hospital and Zhengzhou Central Hospital Affiliated to Zhengzhou University.A dose of 35mg oral TMZ modified release tablet was administered during 2 times of meal a day besides conventional treatments in TMZ group.Conventional treatments to angina were administrated in control group.Forty-six patients finally completed the 3 months' follow-up.Repeated Measures Variance Analysis was used to analyze the effect of TMZ on the outcome variables,including frequency of angina,dominant handgrip strength(HS),pinch strength(PS),gait speed(GS),Five Times Sit-to-Stand Test(FTSST)and Tandem Standing Test(TST).Part 3:D-gal was used to induce senescent C2C12 myoblasts,which were identified by SPiDER-?gal.Differentially expressed genes between different groups and significantly clustered profiles were found by RNA-seq.The up and down-stream of TMZ's targets'expressions were tested by qRT-PCR and WB.Proliferation ability was evaluated by EdU.Total ROS in cells was detected by fluorescent probe H2DCFDA.MMP-9 activity was measured by zymography.ResultsPart 1:The mean age of the elderly participants in the study was 64.6 years.The incidences of LMM were in 18.7%in men and 43.7%in women.Linear regression demonstrated that PBFs were negatively correlated with TMMIs in elderly people(?=-0.990 for men and-0.989 for women,all P<0.001).Logistic regression showed that both men and women with obesity had higher ratios of LMM[Odds Ratio(OR)=16.921 for men and 16.826 for women,all P<0.001].Part 2:In addition to reduce frequency of angina,TMZ increased dominant HS by 24.4%and dominant PS by 12.4%.No side effects have been reported.Part 3:50mM D-gal was used 72h for 10 generations to induce senescent C2C12 myoblasts.RNA-seq results showed that a decreasing trend can be observed after 100?M TMZ intervention in the expressions of NOS3?MMP-9(Profile 18,Q trend<0.001).The expression of OMD(Profile 7,all Q<0.041)and MyoG(Q<0.001)increased after TMZ intervention.qRT-PCR and WB results demonstrated that TMZ can significantly decrease transcription and translation of NOS3(P<0.001 and 0.025,respectively)and translation of MMP-9(P<0.001),but significantly increased transcription and translation of OMD(P=0.008 and<0.001,respectively)and translation of MyoG(P<0.001).EdU staining assay results suggested that there was a significantly increasing trend in proliferation ability after TMZ intervention(P trend=0.020).Fluorescent probe H2DCFDA results indicated that there was a decreasing trend after TMZ intervention in total ROS level trend=0.011).Zymography results implied that there was also a decreasing trend after TMZ intervention in MMP-9 activity(P trend<0.001).ConclusionsPart 1:PBF had a close relationship with TMMI and elderly people with obesity had a higher incidence of LMM.Part 2:TMZ modified release tablets can improve elderly patients' muscle strength,which suggested that it was a safe and effective medicine to elderly patients with stable angina pectoris and poor muscle strength or physical performance.Part 3:Improvement of muscle regeneration by TMZ may have relationship with expressions of NOS3 etc.in senescent C2C12 myoblasts.