A paradoxical role of autophagy: promoting protein aggregates and hindering rejuvenation in a Caenorhabditis elegans L1 arrest model

Macroautophagy (hereafter referred to as autophagy) is widely recognized as a central pathway for the clearance of protein aggregates and the maintenance of proteostasis. However, a recent study by Murley et al. challenges this conventional view. Using a Caenorhabditis elegans L1 arrest aging model, the authors found that autophagy activation impedes rejuvenation by promoting the accumulation of intra- 10 lysosomal protein aggregates and inducing lysosomal membrane damage. This unexpected finding reveals that autophagy may play dual, context-dependent roles in proteostasis, acting not only as a protective mechanism but also, under certain conditions, as a contributor to cellular stress.