Project R-11618

Train your defence system: muscle-derived myokines tackle immune aging by boosting autophagy (Research)

Worldwide population aging leads to new challenges for governments, healthcare and retirement systems. The increase in age-related diseases such as Alzheimer's and cardiovascular disease, and the disabilities often associated with them, causes unseen costs. Exercise represents a powerful tool to extend the healthy life span. While the molecular mechanisms remain unclear, exercise is known to prevent immune aging. Immune aging leads to increased risks of malignancies and autoimmunity, and compromises the response to infections in the elderly. In addition, exercise induces autophagy, the process of 'self-eating'. Aging is accompanied by reduced autophagy, resulting in an increase in misfolded proteins and dysfunctional organelles, causing cellular senescence. When we exercise, muscle cells produce myokines, that subsequently affect metabolic processes in the rest of the body. We hypothesise that exercise-induced myokines improve immunological age by boosting autophagy. Myokines promote our immune defence against infections and tumors through modulation of T cells and natural killer cells, and promote autophagy in these cells. In this project, we define whether neutralisation of exercise-induced myokines lead to impaired autophagy and promote immune aging in an in vivo mouse study. We identify the downstream regulators of myokine mediated autophagy and validate our findings in a human exercise intervention study.

01 January 2021 - 31 December 2024