Growth differentiation factor 15 as a biomarker of frailty: evidence from recent studies

Purpose of review Growth differentiation factor 15 (GDF15), a stress- response protein of the TGF-β superfamily, has emerged as a potential biomarker of frailty. This review aims to summarize recent evidence on the association between GDF15 and frailty. Recent findings Emerging data from 14 recent studies, including seven longitudinal and seven cross-sectional investigations, support GDF15 as a promising biomarker for frailty. Longitudinal studies indicate that elevated GDF15 levels are associated with an increased risk of developing frailty and with adverse outcomes related to frailty over follow-up periods of up to 13 years, across both community-dwelling and clinical populations, such as patients with cardiometabolic diseases or postknee replacement. The predictive value of GDF15 appears to vary depending on the frailty assessment tool used. Cross-sectional analyses corroborate longitudinal findings by showing that GDF15 levels are associated to frailty severity across diverse populations (e.g., community-dwelling, acutely hospitalized patients) in a dose--response manner. Summary GDF15 represents a promising biomarker for frailty, reflecting physical decline and risk of future frailty. Future research should address sex-specific effects, standardize assay protocols and frailty assessments, and explore the clinical utility of GDF15 to detect people at increased risk of decline in intrinsic capacity and frailty in a life course perspective.