Autophagy and Longevity

Abstract

Autophagy is an evolutionally conserved cytoplasmic degradation system in which varieties of materials are sequestered by a double membrane structure, autophagosome, and delivered to the lysosomes for the degradation. Due to the wide varieties of targets, autophagic activity is essential for cellular homeostasis. Recent genetic evidence indicates that autophagy has a crucial role in the regulation of animal lifespan. Basal level of autophagic activity is elevated in many longevity paradigms and the activity is required for lifespan extension. In most cases, genes involved in autophagy and lysosomal function are induced by several transcription factors including HLH-30/TFEB, PHA-4/FOXA and MML-1/Mondo in long-lived animals. Pharmacological treatments have been shown to extend lifespan through activation of autophagy, indicating autophagy could be a potential and promising target to modulate animal lifespan. Here we summarize recent progress regarding the role of autophagy in lifespan regulation.

Keywords: C. elegans; aging; autophagy; longevity; transcription factors.

Fig. 1. Overview of macroautophagy

Upon induction of autophagy by stress, cytoplasmic materials are sequestered by a double-membraned structure, called an autophagosome. These autophagosomes fuse with lysosomes to become autolysosomes, in which the sequestered cargos are degraded and recycled for the maintenance of cellular homeostasis.

Fig. 2. Autophagy is a convergent mechanism of multiple longevity paradigms

Autophagic activity is commonly elevated in many long-lived animals and is essential for their longevity, suggesting that autophagy is one of convergent mechanisms mediating different longevity paradigms.