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

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.