# GDF-15 plasma levels are elevated in mobility-limited older adults with frailty and sarcopenia—results from the BIOFRAIL study

## TL;DR

GDF-15 blood levels are higher in older adults with frailty and sarcopenia, suggesting it could help identify these conditions.

## Contribution

This study shows GDF-15 is a potential biomarker for frailty but not sarcopenia in older adults.

## Key findings

- GDF-15 levels were significantly higher in older adults with frailty compared to those without.
- GDF-15 showed moderate diagnostic accuracy for frailty but poor accuracy for sarcopenia.
- The study identified an optimal cut-off of 2047 pg/mL for GDF-15 to detect frailty.

## Abstract

Growth differentiation factor 15 (GDF-15) has been proposed as a potential biomarker for the geriatric syndromes of frailty and sarcopenia. This study investigated plasma GDF-15 as a biomarker associated with sarcopenia and frailty in a cohort of mobility-limited older adults. Patients (≥ 65 years) were recruited from a geriatric outpatient clinic for fall assessment. Frailty was identified using the Clinical Frailty Scale with a cut-off ≥ 5. Sarcopenia was defined according to the European Working Group on Sarcopenia in Older People 2. Plasma GDF-15 was analyzed using electrochemiluminescence assays (Meso Scale Discovery, Rockville, MD, USA). Receiver operating characteristic (ROC) analysis was performed to assess the diagnostic accuracy of GDF-15 for identifying frailty and sarcopenia. The optimum GDF-15 cut-off for frailty was determined using Youden’s Index. A total of 429 patients (age 79.6 ± 6.2 years, 64% female) were included. Of these, 16% had sarcopenia and 25% had frailty. Median GDF-15 levels in patients with/without sarcopenia and with/without frailty were 1916 pg/mL vs. 1569 pg/mL (p = 0.035), and 2252 pg/mL vs. 1438 pg/mL (p < 0.001), respectively. The area under the curve (AUC) for frailty was 0.681 (95% CI: 0.623–0.739) with an optimal cut-off of 2047 pg/mL. For sarcopenia, AUC was 0.577 (95% CI: 0.501–0.653). GDF-15 plasma levels appear to be elevated in mobility-limited older adults with frailty and sarcopenia. The diagnostic accuracy of GDF-15 for frailty appears of moderate magnitude, suggesting a potential clinical role of this biomarker in identifying frailty in mobility-limited older adults. In contrast, the diagnostic accuracy of GDF-15 for sarcopenia was poor. ClinicalTrials.gov Identifier: NCT05795556.

The online version contains supplementary material available at 10.1007/s11357-025-01946-6.