Autophagy in Aging and Longevity Exemplified by the Aging Heart

Abstract

Cardiovascular diseases are the main cause of death in the aging population worldwide. The aging heart is characterized by a functional and structural impairment of cardiomyocytes, taking shape in the forms of hypertrophy, compromised excitation-contraction coupling, mitochondrial dysfunction, oxidative stress and accumulation of misfolded proteins. In the adult heart, cardiomyocyte regeneration is strictly limited. Therefore, cardiac homeostasis largely depends on mechanisms of cellular quality control. (Macro-)autophagy entails the degradation of macromolecules, protein aggregates and organelles and warrants adaptive protection in diverse situations of cellular stress. Evidently, autophagy is linked to the regulation of aging and longevity. In the heart specifically, autophagy is thought to play a decisive role in the maintenance of cardiomyocyte cell size, proteostasis and mitochondrial function. Due to mechanisms which are not completely understood, autophagy is downregulated in the aging heart. This chapter highlights the emerging role of autophagy in the upkeep of cardiac homeostasis during aging. Current literature on autophagic regulatory signaling via mTOR, AMPK and oxidative stress is discussed for their possible role in the limitation of autophagy in the aging heart. A mitochondria-specific form of autophagy, i.e. mitophagy, is addressed due to its decisive role in cardiac aging.