The PERK paradox in aging: how ER stress shapes senescence and neurodegeneration.

Vivek Pandey, Rahul Sachdeva, Sanda Despa

Department of Physical Medicine and Rehabilitation, University of Kentucky, 2050 Versailles Road, Lexington, KY, 40504, USA. [email protected] of Physical Medicine and Rehabilitation, University of Kentucky, 2050 Versailles Road, Lexington, KY, 40504, USA. [email protected]. · pubmed

Paper

Abstract

Endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) are now recognized as integral components of the proteostasis network that preserves cellular and tissue function across the lifespan. With aging, increasing oxidative load, metabolic imbalance, and Ca

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Research summary

The paper proposes that the PERK pathway exhibits a paradoxical role in aging by driving both cellular senescence and neurodegeneration through endoplasmic reticulum stress, suggesting that modulating this specific UPR branch could mitigate age-related proteostasis decline. This work is relevant as it addresses the root cause of aging by focusing on proteostasis network failure and ER stress, which are fundamental hallmarks of aging, rather than merely treating downstream symptoms.

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