| Title: | Link between Circulating CCL2 Levels and Sarcopenia: Evidence from a Cohort Study, the UK Biobank, and Human GTEx Transcriptomic Data |
| Journal: | Endocrinology and Metabolism |
| Published: | 15 Oct 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42875904/ |
| DOI: | https://doi.org/10.3803/enm.2026.3058 |
Publication 21513
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
Background: Chronic inflammation is a hallmark of aging, but the role of inflammatory mediators such as C-C motif chemokine ligand 2 (CCL2) in skeletal muscle health remains unclear. Although CCL2 is often considered a detrimental pro-aging factor, it is also essential for myogenesis. This study aimed to clarify the complex role of CCL2 in human muscle metabolism.</p>
Methods: We used a multimodal approach integrating clinical, proteomic, transcriptomic, and genetic analyses. The association between circulating CCL2 and sarcopenia-related parameters was examined in 323 community-dwelling older adults and validated using UK Biobank data (n=54,219). Genotype-Tissue Expression (GTEx) transcriptomic data (n=818) were used for tissue-level analysis, and Mendelian randomization (MR) was performed to assess causality.</p>
Results: In the cohort study, serum CCL2 levels were significantly higher in participants with sarcopenia, weak muscle strength, or poor physical performance (P<0.001 to 0.042) and were inversely correlated with skeletal muscle index, grip strength, and gait speed (P<0.001 to 0.003). Each standard deviation increase in circulating CCL2 level was associated with 1.37-1.71-fold higher odds of sarcopenia-related outcomes (all P≤0.028). UK Biobank data also showed higher plasma CCL2 levels in participants with sarcopenia (P=0.005). In contrast to these observational findings, tissue-level analysis using GTEx data showed that higher skeletal muscle CCL2 expression was correlated with greater muscle cross-sectional area. MR further supported an inverse causal association between genetically predicted plasma CCL2 levels and sarcopenia risk (P=0.029).</p>
Conclusion: These divergent findings raise the possibility that elevated circulating CCL2 levels in sarcopenia reflect a compensatory response to muscle deterioration rather than a direct pathogenic driver, highlighting the need for further mechanistic validation.</p>
14 Authors
- Mi Kyung Kwak
- Sung-Jin Kim
- So Jeong Park
- Tam Dao
- Ji Yeon Baek
- Dongryeol Ryu
- June Yeon Kim
- Geon Young Jang
- Eunju Lee
- Hyuk Sakong
- Yuna Lee
- Eun-Gyoung Hong
- Yunju Jo
- Beom-Jun Kim
1 Application
| Application ID | Title |
|---|---|
| 45227 | Scalable and Robust methods for biobank data analysis |
Enabling scientific discoveries that improve human health