APOA1 and APOE proteins related to LXR/RXR pathways as a potential proxy for progression of sarcopenia in community-based prospective cohort

초록

The study aimed to find protein markers as a proxy for the sarcopenia progression, and markers associated with muscle mass and strength..In this prospective community-based cohort study of the geriatric population aged 70-84 years, muscle mass, function, and performance were measured at the baseline and after 2 years. Among them, 63 participants were nonsarcopenic and the baseline but developed severe sarcopenia after 2 years (non-to-sarcopenic group). As the age, sex, and body mass index (BMI)-matched control, 65 participants who stayed nonsarcopenic both at the baseline and follow-up (stayed robust group) and 43 participants who were severe sarcopenic both at the baseline and follow-up (stayed sarcopenic group) were included. We performed liquid chromatography with tandem mass spectrometry using plasma samples. The definition of sarcopenia was based on the Consensus of Asian Working Groups for Sarcopenia in 2019.In baseline characteristics, the mean age of the patients was 78.5 years and 45% were female. Age, BMI, and underlying diseases were similar among groups, while participants in stayed sarcopenic group were more likely to be men than the other groups. In proteomic analysis, ALDOB, LECT2, USP15, KLKB1, KNG1, APOA1, APOA2, TF, OGN, C4BPB, and AXL proteins were differentially expressed between participants in stayed robust and non-to-sarcopenic groups. CSF1R, KLKB1, PRAP1, ICOSLG, CFD, QSOX1, PODXL, CST3, APOA1, APOE, RBP4, AMBP, SLPI, GAPDH, S100A8, S100A9, C7, IGFBP6, PTGDS, LYZ, B2M, EFEMP1, and MMRN2 proteins were differentially expressed between participants in stayed robust and stayed sarcopenic groups. Interestingly, in pathway analysis of differentially expressed proteins, the LXR-RXR pathway, which represents cholesterol efflux, was one of the most significantly associated pathways between participants in stayed robust and non-to-sarcopenic groups. In association analysis with muscle mass and strength, LXR-RXR pathway was also correlated with both muscle mass and strength, and protein-protein interaction analysis showed key proteins of APOE and APOA1 for muscle mass and strength, respectively. Along with the proteomic analysis, baseline serum HDL levels were significantly different among groups, highest in the stayed robust group, and lowest in the stayed sarcopenic group. Baseline HDL levels were negatively associated with baseline and follow-up appendicular muscle mass in the association analysis.In conclusion, the proteomic analysis showed that 11 and 23 proteins were differentially expressed in participants in non-to-sarcopenic, and stayed sarcopenic groups compared to stayed robust group, respectively. The pathway analysis revealed that LXR-RXR pathway was the key pathway to discriminate stayed sarcopenic and non-to-sarcopenic groups and suggested APOE and APOA1 as key protein markers for muscle mass and strength.