Circulating biomarkers in older adults with and without sarcopenia: a systematic review and meta-analysis

Sarcopenia, the age-related loss of muscle mass and strength, poses a significant health and economic burden. This systematic review and meta-analysis evaluates circulating biomarkers (activin A, follistatin, growth differentiation factor (GDF-15), myostatin, growth hormone, insulin growth factor-1 (IGF-1), free and total testosterone) that may be associated with sarcopenia in community-dwelling older adults.

Following PRISMA 2020 guidelines, we searched PubMed, Scopus, Web of Science, and Cochrane Library from inception to June 2025. Studies included adults without major comorbidities aged >60 years with sarcopenia defined by established consensus. Standardized mean differences (SMDs) were calculated using a random-effects model. Heterogeneity was assessed via I2 and meta-regressions, while Egger's test was employed for publication bias.

From 3488 records, 26 observational studies were included (n = 1345 adults with sarcopenia, 48.3% females, mean age 67.9-88.1 years). Adults with sarcopenia showed elevated GDF-15 (k = 5, SMD: 0.26, 95% confidence interval (95% CI), 0.03 to 0.50, I2 = 64%, p = .03) and reduced IGF-1 (k = 11, SMD: -0.40, 95% CI, -0.54 to -0.27, I2 = 36%, p < .01) compared to controls without sarcopenia. No significant differences were found between groups for the other circulating biomarkers.

Elevated circulating IGF-1 and, to a lesser extent, GDF-15, may be promising biomarkers for sarcopenia. Larger, longitudinal studies are needed to address heterogeneity and causality.