Research Overview

Our research primarily focuses on the pathogenesis of sarcopenia and the development of intervention strategies. By integrating clinical skeletal muscle samples with sarcopenia animal models, and employing multi-omics analyses, we aim to comprehensively elucidate the biological basis and underlying pathological mechanisms of sarcopenia. Drawing upon animal survival strategies, we have established a "Small-Molecule Resource Library for Sarcopenia Intervention." Utilizing skeletal muscle cells, Caenorhabditis elegans, and mouse models, we conduct systematic screening, functional validation, and mechanistic studies, with the goal of discovering a series of novel molecules capable of delaying skeletal muscle aging, promoting muscle growth, and improving muscle function, thereby providing new therapeutic targets and innovative strategies for the treatment of sarcopenia.

Our recent findings and ongoing research include the following aspects:

(1) Malnutrition Resistance Factors in Regulating Sarcopenia

Malnutrition is a critical contributing factor to the development of sarcopenia. Drawing upon the survival strategies of amphibians, we have identified a novel class of malnutrition resistance factors—the pore-forming proteins βγ-CAT (Journal of Biological Chemistry, 2020; Zoological Research, 2022, 2023). These proteins bind to acidic glycosphingolipids on the cell membrane, promoting cellular endocytosis of exogenous nutrients and enhancing cell survival under extreme nutritional deprivation (Communications Biology, 2019; Zoological Research, 2021; iScience, 2023). Further studies have revealed that the C. elegans orthologous pore-forming protein LIN-24 regulates lipid metabolism and induces the formation of "donut-shaped mitochondria," thereby conferring resistance to starvation and effectively maintaining skeletal muscle morphology and integrity (Toxins, 2025). Building on these findings, we have also investigated the mammalian orthologous pore-forming protein MPEG1 and discovered its regulatory role in malnutrition-induced skeletal muscle atrophy, suggesting its potential as a therapeutic target for sarcopenia. This work was funded by the National Natural Science Foundation of China in 2024. Currently, we are systematically exploring additional malnutrition resistance factors that may delay sarcopenia, with the expectation of identifying more intervention targets from the perspective of nutritional stress.

(2) Starvation-Induced Metabolic Small Molecules in Regulating Sarcopenia

Based on evolutionarily conserved metabolic pathways that respond to starvation, we have utilized C. elegans and mouse models to investigate the roles of the starvation-induced metabolic small molecule β-hydroxybutyrate (β-HB) and its rate-limiting enzyme HMGCS2 in the pathogenesis of sarcopenia. We found that β-HB-related metabolic enzymes are downregulated during aging across multiple species, and that both exogenous β-HB supplementation and HMGCS2 overexpression effectively delay sarcopenia progression. The underlying mechanism involves increased histone β-hydroxybutyrylation, which promotes the expression of mitochondrial pathway-related genes and subsequently improves mitochondrial function. These findings have been published in Aging Cell (2024), a leading journal in the aging field. To date, we have constructed a starvation-induced metabolic small-molecule library across multiple tissues and organs in mice (Zoological Research, 2026; Biology, 2026), and aim to identify additional small molecules capable of mitigating sarcopenia through starvation-associated metabolic pathways.

(3) Discovery of Novel Molecules for Sarcopenia Intervention

Leveraging our "Small-Molecule Resource Library for Sarcopenia Intervention" established based on animal survival strategies, we have identified multiple candidate molecules with therapeutic potential. First, we screened a compound named Handelin from traditional Chinese medicine and demonstrated its efficacy in delaying sarcopenia progression in mice, with findings published in the Journal of Cachexia, Sarcopenia and Muscle (2023), a leading journal in the field. Second, we discovered that the small peptide OH-CATH30 derived from king cobra venom effectively suppresses cachexia-induced skeletal muscle atrophy via TLR4 signaling, with results published in the Journal of Cachexia, Sarcopenia and Muscle (2026). These discoveries provide novel molecular targets for sarcopenia treatment and highlight the potential of natural products in intervening in age-related diseases.