The stress-responsive cytokine GDF-15 and sarcopenia: A systematic review and meta-analysis on aging muscle decline

BACKGROUND: Given the increasing interest for Growth Differentiation Factor-15 (GDF-15) in muscle decline, this study aims to evaluate the association between circulating levels of GDF-15 and muscle mass and sarcopenia through a systematic review and meta-analysis. METHODS: The research, in accordance with PRISMA and MOOSE guidelines, involved PubMed, Embase, and Cochrane Libraries. Two meta-analyses were performed: (1) comparison of GDF-15 levels in sarcopenic vs non-sarcopenic individuals; (2) correlation between GDF-15 and muscle mass. RESULTS: A total of 7 studies met the inclusion criteria (total n = 2344) enrolling both adults aged ≥ 60 years (6/7 studies) and a younger cohort (42 years [IQR 31.8-51]). The first meta-analysis, based on 4 studies (n = 1393), showed significantly higher levels of GDF-15 in sarcopenic individuals (r = 0.482). The second meta-analysis, involving 4 studies (n = 1400), found a significant inverse correlation between GDF-15 and muscle mass (r = -0.221). CONCLUSIONS: Sarcopenic individuals had higher circulating GDF-15. Together with the inverse correlation between GDF-15 and muscle mass observed, these findings show a small-to-moderate association between elevated GDF-15 and sarcopenic phenotypes in older adults. However, the limited number of studies and high heterogeneity for the sarcopenia comparison warrant cautious interpretation and underscore the need for larger, longitudinal investigations.