Association of GDF15 With Inflammation and Physical Function During Aging and Recovery After Acute Hospitalization: A Longitudinal Study of Older Patients and Age-Matched Controls

J Gerontol A Biol Sci Med Sci. 2021 May 22;76(6):964-974. doi: 10.1093/gerona/glab011.


Growth differentiation factor 15 (GDF15) is a stress-induced cytokine. Its plasma levels increase during aging and acute illness. In older Patients and age-matched Controls, we evaluated whether GDF15 levels (i) were associated with recovery after acute illness, and (ii) reflected different trajectories of aging and longitudinal changes in health measures. Fifty-two older Patients (≥65 years) were included upon admission to the emergency department (ED). At 30 days after discharge (time of matching), Patients were matched 1:1 on age and sex with Controls who had not been hospitalized within 2 years of inclusion. Both groups were followed up after 1 year. We assessed plasma levels of GDF15 and inflammatory biomarkers, frailty, nutritional status (mini nutritional assessment short-form), physical and cognitive function, and metabolic biomarkers. In Patients, elevated GDF15 levels at ED admission were associated with poorer resolution of inflammation (soluble urokinase plasminogen activator receptor [suPAR]), slowing of gait speed, and declining nutritional status between admission and 30-day follow-up. At time of matching, Patients were frailer and overall less healthy than age-matched Controls. GDF15 levels were significantly associated with participant group, on average Patients had almost 60% higher GDF15 than age-matched Controls, and this difference was partly mediated by reduced physical function. Increases in GDF15 levels between time of matching and 1-year follow-up were associated with increases in levels of interleukin-6 in Patients, and tumor necrosis factor-α and suPAR in age-matched Controls. In older adults, elevated GDF15 levels were associated with signs of accelerated aging and with poorer recovery after acute illness.

Keywords: Chronic inflammation; Emergency department; Frailty; Nutritional status; Resilience.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging / blood*
  • Aging / physiology
  • Biomarkers / blood
  • Case-Control Studies
  • Female
  • Frailty / blood
  • Growth Differentiation Factor 15 / blood*
  • Growth Differentiation Factor 15 / physiology
  • Hospitalization / statistics & numerical data*
  • Humans
  • Inflammation / blood*
  • Inflammation / physiopathology
  • Longitudinal Studies
  • Male
  • Mental Status and Dementia Tests
  • Physical Functional Performance*
  • Prospective Studies
  • Recovery of Function


  • Biomarkers
  • GDF15 protein, human
  • Growth Differentiation Factor 15