A Review of Omics Studies in Sarcopenia: From Molecular Mechanisms to Hepatic-Gut-Muscle Interactions in Chronic Liver Disease Comorbidity

Zhengtao Liu^1*Xiaohui Xue¹Jun Xu²Huijuan Wang¹Kainan Wang¹Yumu Chen¹Yiting Xu¹Shuping Que³

• ¹Zhejiang Shuren University Key Laboratory of Artificial Organs and Computational Medicine, Hangzhou, China
• ²NHC Key Laboratory of Combined Multi-Organ Transplantation, Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
• ³Ya-er-zhuang Clinics, Hangzhou, China

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.