Senolytics and exercise: Dual modalities for rejuvenating muscle

Mammalian ageing is defined as a gradual loss of the capacity to maintain tissue homeostasis or to repair tissues after injury or stress. Cellular senescence is induced by various cellular stressors, and there is accumulation of senescent cells in all tissues with ageing and chronic disease, which contributes to pathophysiology and organ deterioration. Long-term persistence of senescent cells and their senescence-associated secretory phenotype (SASP) impairs tissue homeostasis and regenerative capacity, leading to tissue and physiological dysfunction. Senolytics are senotherapeutic agents that systemically eliminate senescent cells, and have been shown in pre-clinical and clinical studies to improve cardiac and skeletal muscle regeneration, remodelling and physiological function. Exercise training and physical activity have also been shown to have senolytic effects. In this review, we evaluate whether targeting cell senescence using senolytics can rejuvenate the heart and skeletal muscle, reversing the ageing phenotype.