Overview
- Advanced imaging and genetics in living C. elegans showed ER components accumulating in lysosomes during aging, indicating active, selective ER turnover.
- Blocking core autophagy genes prevented age-dependent ER loss, while disrupting unfolded protein response branches did not, separating ER-phagy from ER-stress signaling.
- Aging cells sharply reduced rough ER involved in protein production, with only slight impact on tubular ER associated with lipid synthesis.
- The remodeling program was seen across neurons, muscle, intestine, and hypodermis and was conserved in yeast through autophagy-dependent vacuolar trafficking.
- TMEM-131’s LC3-interacting region was required to couple ER membranes to autophagosomes, and ER remodeling aligned with multiple lifespan-extending pathways.