Associations Between Growth Differentiating Factor‐15 and Frailty in Older Adults From the MAPT Study

BACKGROUND: Frailty is a prevalent syndrome in older adults and is associated with increased vulnerability to adverse health outcomes. Growth differentiation factor 15 (GDF-15), a cytokine involved in mitochondrial dysfunction and inflammation, has been proposed as a potential biomarker for age-related conditions. Evidence on the association between GDF-15 and frailty in older adults is limited. This study explores the relationship between plasma GDF-15 levels and frailty onset in community-dwelling older adults. METHODS: A secondary analysis was performed on 1096 participants (mean age = 75.2 ± 4.5 years; 64.5% women) from the Multidomain Alzheimer Prevention Trial (MAPT). Plasma GDF-15 levels were measured at year 1. Frailty was assessed using the Fried phenotype. Logistic regression was used to examine cross-sectional associations between GDF-15 and frailty, while mixed effects logistic regression or Cox proportional hazards models assessed longitudinal associations over a 4-year follow-up. RESULTS: Higher plasma GDF-15 levels (both as continuous and categorical) were cross-sectionally associated with frailty (high vs. low GDF-15: OR = 3.56, 95% CI = 1.58-8.03). Longitudinally, very high GDF-15 levels predicted an increased risk of incident frailty (HR = 1.69, 95% CI = 1.03-2.78). CONCLUSIONS: Elevated plasma GDF-15 levels were associated with frailty in older adults, suggesting its potential as a biomarker for increased vulnerability and an indicator of increased risk over time. Our results support a pleiotropic role of GDF-15, with low physiological levels not contributing to frailty development.