Central role of the ER proteostasis network in healthy aging.

Claudio Hetz, Andrew Dillin

The Buck Institute for Research in Aging, Novato, CA 94945, USA; Center for Geroscience, Brain Health, and Metabolism (GERO), Santiago, Chile; Biomedical Neuroscience Institute (BNI), Faculty of Medicine, University of Chile, Santiago, Chile; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences (ICBM), University of Chile, Santiago, Chile. Electronic address: [email protected]. · pubmed

Paper

Abstract

Aging trajectories vary among individuals, characterized by progressive functional decline, often leading to disease states. One of the central hallmarks of aging is the deterioration of proteostasis, where the function of the endoplasmic reticulum (ER) is dramatically affected. ER stress is monitored and adjusted by the unfolded protein response (UPR); a signaling pathway that mediates adaptive processes to restore proteostasis. Studies in multiple model organisms (yeast, worms, flies, and mice) in addition to human tissue indicates that adaptive UPR signaling contributes to healthy aging. Strategies to improve ER proteostasis using small molecules and gene therapy reduce the decline of organ function during normal aging in mammals. This article reviews recent advances in understanding the significance of the ER proteostasis network to normal aging and its relationship with other hallmarks of aging such as senescence.

The following analysis is generated by AI and may contain errors. It is separate from the authors’ abstract and is not peer review.

Research summary

The paper addresses the role of the endoplasmic reticulum (ER) proteostasis network in healthy aging, which is directly related to the mechanisms of aging and the maintenance of cellular function over time. It discusses adaptive UPR signaling and its potential to improve proteostasis, thereby contributing to healthier aging and possibly extending lifespan. The findings are significant as they advance our understanding of a fundamental aspect of aging, but they do not represent a groundbreaking breakthrough that would transform the field, hence the score of 5.

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