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Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. An Author Correction to this article was published on 02 January Senescent cells drive age-related tissue dysfunction partially through the induction of a chronic senescence-associated secretory phenotype SASP 1.

Mitochondria are major regulators of the SASP; however, the underlying mechanisms have not been elucidated 2. Mitochondria are often essential for apoptosis, a cell fate distinct from cellular senescence. During apoptosis, widespread mitochondrial outer membrane permeabilization MOMP commits a cell to die 3. Here we find that MOMP occurring in a subset of mitochondria is a feature of cellular senescence.

We find that inhibition of MOMP in vivo decreases inflammatory markers and improves healthspan in aged mice. Our results reveal that apoptosis and senescence are regulated by similar mitochondria-dependent mechanisms and that sublethal mitochondrial apoptotic stress is a major driver of the SASP.

We provide proof-of-concept that inhibition of miMOMP-induced inflammation may be a therapeutic route to improve healthspan. Cellular senescence refers to the irreversible growth arrest that occurs as a response to different stressors 1 , 4.