Targeting Autophagy in Aging and Aging-Related Cardiovascular Diseases

Aging, an irreversible biological process, serves as an independent risk factor for chronic disease including cancer, pulmonary, neurodegenerative, and cardiovascular diseases. In particular, high morbidity and mortality have been associated with cardiovascular aging, but effective clinical therapeutic remedies are suboptimal for the ever-rising aging population. Recent evidence suggests a unique role for aberrant aggregate clearance and the protein quality control machinery - the process of autophagy - in shortened lifespan, compromised healthspan, and the onset and development of aging-associated cardiovascular diseases. Autophagy degrades and removes long-lived or damaged cellular organelles and proteins, the functions of which decline with advanced aging. Induction of autophagy using rapamycin, resveratrol, nicotinamide derivatives, metformin, urolithin A, or spermidine delays aging, prolongs lifespan, and improves cardiovascular function in aging. Given the ever-rising human lifespan and aging population as well as the prevalence of cardiovascular disease provoked by increased age, it is pertinent to understand the contribution and underlying mechanisms of autophagy and organelle-selective autophagy (e.g., mitophagy) in the regulation of lifespan, healthspan, and cardiovascular aging. Here we dissect the mechanism of action for autophagy failure in aging and discuss the potential rationale of targeting autophagy using pharmacological agents as new avenues in the combating of biological and cardiovascular aging.