ORIGINAL RESEARCH article
Front. Med.
Sec. Geriatric Medicine
Volume 12 - 2025 | doi: 10.3389/fmed.2025.1515839
Associations between sarcopenia (defined by low muscle mass), inflammatory markers, and all-cause mortality in older adults: Mediation analyses in a large U.S. NHANES community sample, 1999-2006
Provisionally accepted
- Peking University Third Hospital, Haidian, China
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Background: Sarcopenia is linked to increased mortality, but the specific role of inflammation in sarcopenia-related mortality remains poorly understood. This study aims to integrate various inflammatory biomarkers to develop an inflammation prognostic score (IPS) within the large, representative NHANES cohort. It also explores the association between sarcopenia, inflammatory markers, and mortality, and investigates whether inflammation mediates this relationship.Methods: This study analyzed data from NHANES (1999–2006) on 3,544 participants aged 65 and older, with mortality follow-up through December 31, 2019, using death records from the National Death Index (NDI). Statistical analyses accounted for complex survey design and multiple imputation for missing data. Sarcopenia was defined using appendicular skeletal mass adjusted for BMI. Cox regression assessed the association between sarcopenia, inflammatory markers, and all-cause mortality. The IPS was developed using LASSO regression, and mediation analysis was conducted to assess whether inflammatory markers mediate the relationship between sarcopenia and mortality. Results: Among 3,544 elderly participants, sarcopenia was present in 25.4%, with a 66.6% overall mortality rate during the follow-up period. Multivariate Cox regression confirmed that sarcopenia is an independent risk factor for mortality (HR = 1.235–1.281, p < 0.001). Inflammatory markers were significantly associated with all-cause mortality. The IPS showed a clear trend of increasing mortality risk across quartiles, with HR reaching 2.044 in Q4 (p < 0.001). Mediation analysis showed that IPS mediated 20.8% of the relationship between sarcopenia and mortality, with the mediating effect remaining significant after adjusting for confounders.Conclusion: This study confirms the association between sarcopenia and increased mortality risk, with inflammation as a key mediating factor, highlighting its role in sarcopenia-related mortality.
Keywords: Sarcopenia, NHANES (National Health and Nutrition Examination Survey), Inflammation, older adults, Mortality
Received: 23 Oct 2024; Accepted: 13 Jun 2025.
Copyright: © 2025 Liu and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Fuchun Zhang, Peking University Third Hospital, Haidian, China
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