Mild activation of the mitochondrial unfolded protein response increases lifespan without increasing resistance to stress.

Alexa Di Pede, Bokang Ko, Abdelrahman AlOkda, Aura A Tamez González, Shusen Zhu, Jeremy M Van Raamsdonk

Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada. · pubmed

Paper

Abstract

The mitochondrial unfolded protein response (mitoUPR) is a stress response pathway that responds to mitochondrial insults by altering gene expression to recover mitochondrial homeostasis. The mitoUPR is mediated by the stress-activated transcription factor ATFS-1 (activating transcription factor associated with stress 1). Constitutive activation of ATFS-1 increases resistance to exogenous stressors but paradoxically decreases lifespan. In this work, we determined the optimal levels of expression of activated ATFS-1 with respect to lifespan and resistance to stress by treating constitutively active

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Research summary

Mild activation of the mitochondrial unfolded protein response can increase lifespan without enhancing stress resistance. This research is relevant as it explores mechanisms that could potentially influence lifespan extension by modulating mitochondrial stress responses, which are critical in the context of aging.

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