Caloric restriction rejuvenates myofiber growth in heart failure

Heart failure with preserved ejection fraction (HFpEF) is characterised by a distinct but poorly understood in skeletal muscle pathology. In a rat model ZSF1, we identify impaired myonuclear accretion as a mechanism for ablated myofiber growth in HFpEF following resistance exercise intervention. Muscle vascular or mitochondrial dysfunction, or impaired protein synthesis signalling, do not appear as primary limiting mechanisms, and cardiac therapies do not attenuate skeletal muscle pathology. However, we identify that acute caloric restriction rejuvenates myofiber growth in HFpEF during resistance exercise intervention.