GDF-15: a mediator of exercise’s link with late-life weight loss?

Ageing is often associated with appetite reduction and ensuing weight loss. Although it is known that physical activity (PA) can prevent these ageing-related processes, the exact molecular mechanisms underpinning this ability remain unknown. Recent research has highlighted the role of exerkines, i.e. proteins released during and after PA, in controlling energy metabolism. Growth differentiation factor 15 (GDF-15), a stress-signalling cytokine secreted during PA and involved in ageing, exercise, and appetite control, has emerged as a potential mediator of late-life, ageing-related weight loss.

This study aimed to explore the associations between PA, GDF-15, and body weight changes in older adults enrolled in the Multidomain Alzheimer Preventive Trial over a 3-year period.

Key learnings:

Higher mean PA levels, including total physical activity volume (mTPA) and moderate to vigorous physical activity volume (mMVPA) but not light physical activity volume, predicted lower body weight and circulating GDF-15 levels at the 1-year mark. Furthermore, higher GDF-15 levels at the 1-year visit predicted faster weight loss over the next 2 years. Importantly, however, mediation analyses revealed that mean PA exerted no direct effects on body weight: instead, GDF-15-mediated mTPA and mMVPA levels correlated with weight loss over time. Indeed, higher GDF-15-mediated mTPA and mMVPA levels were found to be associated with reduced weight loss noted at the 1- and 3-year marks. These findings identify GDF-15 as a pivotal mediator of PA’s effects on late-life weight loss; a conclusion which remains to be tested mechanistically.

Reviewed by: S. Duarte