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Published on: February 21, 2025
233
Causal Relationship Between Circulating Metabolites and Sarcopenia-Related Traits: A Mendelian Randomization and
Weihui Qi1,2,3, Xinning Mao1, Zhenglin Mei1
1Department of Orthopaedics Hangzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University Hangzhou China.
Food Science & Nutrition
|January 13, 2025
Summary
This study reveals causal links between specific metabolites, like glycine, and sarcopenia (SP), a condition of age-related muscle loss. These findings highlight potential biomarkers for early detection and intervention strategies for sarcopenia.
Area of Science:
- Metabolomics
- Gerontology
- Genetics
Background:
- Sarcopenia (SP) is linked to metabolic factors, but causal relationships and pathways are unclear.
- Understanding these links is crucial for developing interventions for age-related muscle loss.
Purpose of the Study:
- To investigate causal associations between serum metabolites and sarcopenia using Mendelian randomization (MR).
- To identify biological signaling pathways involved in the metabolite-sarcopenia connection.
- To explore metabolite expression in an animal model of sarcopenia.
Main Methods:
- Bidirectional two-sample Mendelian randomization (MR) analysis of 1091 metabolite levels and 309 ratios with SP traits.
- Analysis of differential plasma metabolite expression and signaling pathways in an animal model.
- Bonferroni's correction and multiple contrast correction for statistical significance.
Main Results:
- Identified 11 robust causal associations between seven metabolite levels/ratios and SP traits.
- Validated a stable causal association between glycine levels and SP.
- Reverse MR analysis revealed 11 strong causal relationships between plasma metabolites and SP.
- Pathway analysis implicated glycine metabolism, insulin resistance, and cAMP signaling.
Conclusions:
- Glycine metabolism is strongly associated with sarcopenia, supported by MR and animal model data.
- Identified metabolites and pathways can serve as biomarkers for sarcopenia screening and prevention.
- These findings offer potential targets for future mechanism exploration and drug development.
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