Molecular Basis of Neuronal Autophagy in Ageing: Insights from Caenorhabditis elegans

Abstract

Autophagy is an evolutionarily conserved degradation process maintaining cell homeostasis. Induction of autophagy is triggered as a response to a broad range of cellular stress conditions, such as nutrient deprivation, protein aggregation, organelle damage and pathogen invasion. Macroautophagy involves the sequestration of cytoplasmic contents in a double-membrane organelle referred to as the autophagosome with subsequent degradation of its contents upon delivery to lysosomes. Autophagy plays critical roles in development, maintenance and survival of distinct cell populations including neurons. Consequently, age-dependent decline in autophagy predisposes animals for age-related diseases including neurodegeneration and compromises healthspan and longevity. In this review, we summarize recent advances in our understanding of the role of neuronal autophagy in ageing, focusing on studies in the nematode Caenorhabditis elegans.

Keywords: Caenorhabditis elegans; ageing; autophagy; macroautophagy; neurodegeneration; neuronal autophagy.

Figure 1

Overview of the autophagy process in human. (A). Schematic representation of autophagosome formation and cargo degradation. Complete autophagosomes may fuse with endosomes to form amphisomes, which further fuse with lysosomes. (B). Omegasome and isolation membrane generation. (C). Isolation membrane expansion, LC3 processing and autophagic substrate sequestration. Additional membrane sources may contribute to isolation membrane formation and expansion. SAR: selective autophagy receptor, LC3-GKLSV: pro-LC3, LC3-G: LC3-I, LC3-G-PE: LC3-II.