Autophagy in proteostasis and aging in Caenorhabditis elegans

Abstract

Proteostasis (protein homeostasis), the balance of protein synthesis, folding, and degradation, is critical for cellular function and organismal health. Its disruption leads to the accumulation of misfolded and aggregated proteins, hallmarks of aging and age-related diseases, including neurodegeneration. Autophagy, a conserved lysosome-mediated degradation pathway, is central to proteostasis by clearing toxic proteins and damaged organelles. In Caenorhabditis elegans, studies across conserved longevity paradigms and models of neurodegenerative diseases have defined key mechanisms by which autophagy maintains proteostasis during aging and stress. Beyond its degradative functions, autophagy contributes to spatial quality control by promoting the formation of potentially protective protein inclusions and coordinating with the ubiquitin-proteasome system. Emerging evidence also points to noncanonical autophagy pathways, such as unconventional secretion and inter-tissue communication, that broaden its role in systemic proteostasis. Together, these advances underscore autophagy’s multifaceted contribution to protein quality control, with wide-ranging implications for aging, stress resistance, and neurodegenerative disease.