Biological Aging of Human Skeletal Muscle

The age-related loss of skeletal muscle mass and function (sarcopenia) is one of the most dramatic changes affecting the human body. A clear understanding of the mechanisms involved is thus of paramount importance in ensuring quality of life in the old age. Most previous studies of sarcopenia in human investigated chronological aging, as they relied on comparisons between young and old subjects. Notably, no previous study has taken into consideration inter-individual differences (biological aging) in prevalence of sarcopenia. To obtain an integrative view of muscle biological aging our project uses a single biopsy from 72 well-phenotyped 80 years healthy subjects with different muscle loss/gain (PROOF cohort), to provide an extended characterization of the muscle tissue, including microstructural and omic analyses. Overall design: To obtain an integrative view of biological aging, the research program 4 components encompassing: metabolomic, cellular, transcriptomic and proteomic parameters. We assess biological aging in both men and women by comparing groups with either decreased, increased or stable appendicular lean mass (ALM).

与年龄相关的骨骼肌质量流失与功能衰退（肌肉减少症，sarcopenia）是影响人体的最显著衰老相关变化之一。明确阐明其背后的潜在机制，对于提升老年群体的生活质量至关重要。既往绝大多数人类肌肉减少症相关研究均围绕时序衰老（chronological aging）展开，此类研究多通过对比年轻与老年受试者的数据完成。值得注意的是，此前尚无研究考虑到肌肉减少症患病率存在的个体间差异（即生物学衰老，biological aging）。
为全面解析肌肉生物学衰老的整合性图景，本项目选取72名表型特征明确的80岁健康受试者的单次肌肉活检样本（这些受试者的肌肉流失/增加情况各不相同，即PROOF队列），对肌肉组织开展多维度深度表征分析，涵盖微观结构检测与组学分析。
整体研究设计：为系统构建生物学衰老的整合视角，本研究项目包含四大研究模块，涵盖代谢组学（metabolomics）、细胞生物学（cellular biology）、转录组学（transcriptomics）与蛋白质组学（proteomics）相关参数。我们将通过对比肢体瘦体重（appendicular lean mass, ALM）分别降低、增加或保持稳定的男性与女性群体，评估其生物学衰老水平。