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

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.

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.

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.