The mitochondrial integrated stress response: A novel approach to anti-aging and pro-longevity

Xiaoding Wang; Guangyu Zhang

doi:10.1016/j.arr.2024.102603

The mitochondrial integrated stress response: A novel approach to anti-aging and pro-longevity

Ageing Res Rev. 2025 Jan:103:102603. doi: 10.1016/j.arr.2024.102603. Epub 2024 Nov 26.

Authors

Xiaoding Wang¹, Guangyu Zhang²

Affiliations

¹ Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan 430030, China. Electronic address: xiaoding.wang@tjh.tjmu.edu.cn.
² Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan 430030, China. Electronic address: guangyu.zhang@tjh.tjmu.edu.cn.

PMID: 39608727
DOI: 10.1016/j.arr.2024.102603

Abstract

The ISR is a cellular signaling pathway that responds to various physiological changes and types of stimulation. The mitochondrial integrated stress response (ISR^mt) is a stress response specific to mitochondria which is initiated by eIF2α phosphorylation and is responsive to mitochondrial stressors. The ISR^mt triggers diverse metabolic responses reliant on activating transcription factor 4 (ATF4). The preliminary phases of ISR^mt can provoke an adaptive stress response that antagonizes age-related diseases and promotes longevity. In this review, we provide an overview of the molecular mechanisms of the ISR^mt, with a particular focus on its potential as a therapeutic target for age-related disease and the promotion of longevity.

Keywords: Aging; FGF21; Longevity; Mitochondrial integrated stress response.

Publication types

Review

MeSH terms

Aging* / metabolism
Aging* / physiology
Animals
Humans
Longevity* / drug effects
Longevity* / physiology
Mitochondria* / metabolism
Signal Transduction / physiology
Stress, Physiological* / physiology