Autophagy: A Double-Edged Sword in the Aging of C. elegans

Autophagy is a tightly regulated catabolic process essential for cellular homeostasis, stress adaptation, and regeneration. In the nematode Caenorhabditis elegans, with its short lifespan, transparent body, and well-defined genetics, the process can be investigated in a tissue- and age-specific manner, making it an excellent model to study the connection between autophagy and longevity. While autophagy is generally protective-promoting cellular maintenance and longevity-its dysregulation or hyperactivation during aging can be deleterious, leading to cellular stress, tissue damage, and cell death. In this context, autophagy can act as a double-edged sword: its beneficial effects can become harmful if hyperactivated or improperly controlled, particularly in post-reproductive or stressed tissues. Here, we review studies in C. elegans that link autophagy to lifespan regulation, with a focus on unexpected, context-dependent, or harmful effects of modulating autophagy-related genes during aging. We highlight how age- and tissue-specific regulation of autophagy can optimize its protective role and discuss the implications of these findings for designing strategies to promote healthy aging, potentially providing insights for the therapeutic targeting of autophagy in humans.