Role of autophagy in aging.

Constitutive autophagy is important for the control of the quality of proteins and organelles to maintain cell function. Damaged proteins and organelles accumulate in aged organs. The level of autophagic activity decreases with aging. Autophagic activity is regulated by many factors, such as the insulin receptor-signaling pathway, the TOR pathway, Sirt1, and caloric restriction. Autophagy-related genes are known to be essential for the lifespan extension of flies, nematodes, and mice. The inhibition of autophagy decreases the lifespan, and on the other hand, the induction of autophagy can prolong the lifespan. Pharmacological intervention to extend the lifespan has demonstrated a crucial role for autophagy. Heart failure is an age-related disease, as the incidence increases with age. The autophagic activity of the heart decreases during aging. Cardiac-specific autophagy-deficient mice have shown no obvious phenotype up to 10 weeks of age. However, these mice began to die after the age of 6 months, with a significant increase in the left ventricular dimensions and a decrease in the fractional shortening of the left ventricle compared with control mice. This indicates that continuous constitutive autophagy during aging has a crucial role in maintaining cardiac structure and function.