Project R-15588

A glitch in the matrix: characterization of the potential of ketone bodies to improve muscular and functional adaptations to exercise training in young and older adults. (Research)

We recently indicated that increasing blood ketone levels, by ketone ester ingestion (KE), promotes muscular angiogenesis and net muscle anabolism during exercise training performed under catabolic conditions. In addition, we provided proof of concept for a beneficial role of KE in remodeling of the extracellular matrix (ECM), and in promoting post-exercise sleep, which are both central players in the adaptive response to exercise. Therefore, we aim to elucidate whether KE, via these alterations, can beneficially impact the muscular and functional response to exercise training in well-trained individuals. Given the pivotal role of muscle catabolism, capillary rarefaction, sleep disturbances, and ECM remodeling in the age-related decline of muscular function and general health, we also aim to identify the effect of KE on the adaptive response to exercise training in older adults. In both work packages, we will provide an in-depth blueprint of the adaptations that occur in the skeletal muscle ECM as this is increasingly recognized to be a central regulator of muscular plasticity. As such, we aim to provide a detailed understanding of the effects of KE, exercise training, and aging on skeletal muscle ECM. This project will thus not only benefit athletes, but will also provide direct relevance for older adults, and will support the development of clinical trials in the context of dystrophic syndromes and other clinical models that are characterized by ECM dysregulations.

16 August 2024 - 30 September 2026