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Updated: Feb 28, 2026

Using Caenorhabditis elegans as a Model System to Study Protein Homeostasis in a Multicellular Organism
Published on: December 18, 2013
The UPRER: Sensor and Coordinator of Organismal Homeostasis
Ashley E Frakes1, Andrew Dillin1
1Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; The Glenn Center for Aging Research at UC Berkeley, Berkeley, CA 94720, USA.
Abstract:
Life is stressful. Organisms are repeatedly exposed to stressors that disrupt protein homeostasis (proteostasis), resulting in protein misfolding and aggregation. To sense and respond to proteotoxic perturbations, cells have evolved compartment-specific stress responses, such as the unfolded protein response of the endoplasmic reticulum (UPRER). However, UPRER function is impaired with age, which, we propose, creates a permissive environment for protein aggregation, unresolved ER stress, and chronic inflammation. Understanding age-related changes to the UPRER will provide new avenues for therapeutic intervention in metabolic disease, neurodegeneration, and aging.
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