Growth differentiation factor-15 as a clinical biomarker of frailty, sarcopenia and functional decline: A systematic literature review.
Level 3 - non-randomized controlled study
Systematic review of predominantly observational and cohort studies
PubMed 41785972 · doi:10.1016/j.arr.2026.103085
What was done
Systematic literature review following PRISMA guidelines searching CENTRAL, Embase, MEDLINE, and PubMed through February 2026. The authors included adult human studies measuring serum GDF-15 alongside assessments of frailty or sarcopenia across diverse populations (community-dwelling, hospitalized, and disease-specific cohorts). Data were synthesized narratively across study design, population, and outcome domains.
What was found
Thirty-five studies (from 1,027 initial records) were included. Elevated GDF-15 levels were consistently associated with poorer physical performance and higher frailty severity. Longitudinal cohorts supported its value in predicting future functional decline, while associations with sarcopenia were less consistent. Interventional studies showed limited modulation of GDF-15 levels by physical activity alone. The abstract reports no numerical effect sizes, correlation coefficients, or pooled statistics.
Why it matters
This review synthesizes clinical evidence supporting GDF-15 as an integrative biomarker of biological aging and physical decline across varied clinical settings.
Limits
No quantitative meta-analysis was performed; findings are limited to narrative synthesis. The underlying studies exhibit substantial methodological heterogeneity in assay techniques and diagnostic definitions of frailty/sarcopenia, alongside sex-specific variations and inconsistent associations with sarcopenia.
Cited by
- supports Higher circulating levels of GDF15 are epidemiologically associated with reduced engagement in voluntary physical activity, such as walking for pleasure and climbing stairs.