Xiaohui Xue, Jun Xu, Huijuan Wang, Kainan Wang, Yumu Chen, Yiting Xu, Shuping Que, Zhengtao Liu
Sarcopenia is an aging-related skeletal-muscle disorder characterized by progressive loss of muscle mass, strength, and function, and it frequently co-occurs with chronic liver disease (CLD) and other comorbidities. Conventional approaches struggle to resolve its pronounced heterogeneity, whereas multi-omics technologies now offer a systematic, molecular-level avenue to dissect its pathogenesis. By integrating ten omics studies of sarcopenia and six of CLD-associated sarcopenia, we propose a dual-layer "commonality-specificity" framework. At the level of commonality, we identify four core pathological pillars: proteostasis imbalance, mitochondrial dysfunction, chronic inflammation, and dysregulation of the gut-muscle axis. At the specificity level, focusing on the CLD context, we observe that these networks are selectively perturbed within the liver-disease microenvironment, leading us to advance the "cooperative accumulation of multiple weak signals" hypothesis to explain how multi-axis crosstalk drives muscle wasting in this setting. To date, omics findings remain largely correlational, posing challenges for clinical translation. Future investigations should integrate cutting-edge technologies-such as single-cell multi-omics, spatial transcriptomics, and computational modeling-to shift the research paradigm from static profiling to dynamic mechanistic dissection and precision intervention. This review provides both a theoretical foundation and a developmental roadmap for comprehensively understanding the mechanisms underlying sarcopenia comorbidities and for achieving precision diagnosis and treatment.