Autophagy-A key pathway for cardiac health and longevity.

As average life expectancy continues to rise in the developed world, age-associated pathologies are increasing in prevalence. The hallmarks of cardiac ageing include cardiomyocyte loss, fibrosis and hypertrophy, all of which contribute to an increased incidence of cardiac disease. At the molecular level, cellular ageing is characterized by increased ROS production, mitochondrial dysfunction and the accumulation of damaged proteins and organelles. Cardiomyocytes and other senescent cell types rely upon autophagy, a lysosome-mediated degradation pathway, to remove potentially toxic protein aggregates and damaged organelles from the cellular milieu. However, increasing lines of evidence point to an age-associated decrease in cardiomyocyte autophagy, with predictably negative consequences for cardiac function and health. Conversely, stimulation of autophagy has been shown to improve cellular health and cardiac function and to increase lifespan in numerous model organisms. Clearly, autophagy represents a critical pathway for cellular vitality, as well as a promising therapeutic target for the treatment of age-related cardiac pathologies. In this review, we will discuss the mechanism of autophagy and its regulation in the cell, the role of autophagy in the ageing heart, and how the autophagy pathway might be targeted to improve cardiac health. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.