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A C. elegans-to-Mouse Discovery Framework for Prioritizing Sarcopenia Interventions
Yejin Cho1,2, Hyo-Deok Seo1, Chang Hwa Jung1,2
1Aging Research Group, Korea Food Research Institute, Wanju-gun, Republic of Korea.
Aging and Disease
|July 27, 2026
Summary
Developing sarcopenia therapies is challenging. A new C. elegans-to-mouse framework rapidly screens interventions, prioritizing candidates based on function preservation for skeletal muscle aging.
Area of Science:
- Gerontology and Muscle Biology
- Drug Discovery and Development
Background:
- Sarcopenia, a key aspect of musculoskeletal aging, lacks approved therapies, hindering effective treatment development.
- Identifying promising sarcopenia interventions is difficult due to the vast diversity of potential candidates and the limitations of aged-mammal models for initial screening.
Purpose of the Study:
- To propose and describe a C. elegans-to-mouse discovery framework for accelerating the development of sarcopenia interventions.
- To outline a strategy for efficient early-stage prioritization of therapeutic candidates for skeletal muscle aging.
Main Methods:
- Utilizing Caenorhabditis elegans (C. elegans) for rapid, organism-level assessment of locomotor function, muscle integrity, and conserved aging mechanisms.
- Screening diverse candidate interventions, including natural products and compounds, in C. elegans to prioritize candidates for further validation in aged-mammal models.
- Integrating function-centered screening with conserved biological mechanisms (e.g., mitochondrial quality control, proteostasis) for cross-species interpretation.
Main Results:
- The C. elegans model allows for efficient screening of large candidate pools, including various compounds, doses, and combinations.
- Preservation of age-related function in C. elegans serves as a primary criterion for selecting interventions.
- Examples like urolithin A, norharmane, and spermidine demonstrate successful integration of worm-based screening with mechanistic data and mouse validation.
Conclusions:
- A C. elegans-to-mouse framework enhances the prioritization of sarcopenia interventions by combining functional screening with mechanistic insights.
- This approach accelerates the discovery of function-preserving therapeutics for age-related skeletal muscle decline.
- The proposed framework offers a practical strategy to overcome challenges in sarcopenia intervention development.
