Exercise-Induced Changes in Circulating Exerkines Associated with Brain Health: A Systematic Review and Meta-Analysis in Healthy Populations

Exerkines are released in response to physical exercise and play a key role in promoting health, such as taking part in modulating brain morphology and function. Expression levels of some of them are associated with an increase in neuroplasticity and a decrease in the risk of brain-related diseases such as dementia and depression. Therefore, our objective is to investigate the response of exerkines in healthy individuals and its potential to promote brain health. The search was performed in five databases. Randomized controlled trials of humans and animals of all ages who performed acute and/or long-term exercise and assessed the effects of exerkines were included. Human data were used for quantitative analysis, and animal experiments were included as part of the qualitative analysis. No meta-analyzes were conducted on animal data; preclinical findings are presented solely to contextualize mechanisms and are not used for clinical inference. Eventually, the sample consisted of 3321 individuals, with an age range from 10 to 89 years. Meta-analysis reveals that both acute and chronic exercise induced increases in the brain-derived neurotrophic factor and insulin-like growth factor 1 in older adults. Other exerkines such as cathepsin B and vascular endothelial growth factor have also demonstrated potential power for brain health. In conclusion, physical exercise by altering the levels of exerkines may be a feasible strategy for healthy individuals aiming at healthy aging of the brain. Moreover, it is advisable to analyze additional exerkines or multiple simultaneous applications to assess the cerebral effects during physical exercise. PROSPERO registration number: CRD42023438803.