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Cytosolic mitochondrial nucleic acids activate innate immune signalling to initiate this inflammatory programme\n                    <jats:sup>2,3<\/jats:sup>\n                    . Here we show that mitochondrial metabolism provides a second layer of control that enables execution of the inflammatory programme. In senescent cells, the mitochondrial pyruvate\u2013citrate\u2013acetyl-CoA axis is upregulated, increasing the availability of acetyl-CoA to support histone acetylation at SASP genes. Whereas mitochondrial DNA-driven signalling activates inflammatory transcription factors, acetyl-CoA availability is required for robust transcription of SASP genes. Accordingly, enhancing acetyl-CoA levels promotes SASP gene expression, whereas inhibition of SLC25A1, the mitochondrial citrate exporter, reduces histone acetylation at SASP loci, limiting activity of this programme. In vivo, inhibition of SLC25A1 reduces chromatin accessibility at SASP loci, dampens inflammation and improves healthspan in aged mice. Together, these findings identify a mitochondrial metabolic checkpoint that enables the epigenetic execution of innate immune signalling, revealing a mechanism that selectively controls the inflammatory output of senescent cells.\n                  <\/jats:p>","DOI":"10.1038\/s41586-026-10791-2","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T15:02:19Z","timestamp":1785337339000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mitochondrial metabolism and epigenetic crosstalk drive SASP"],"prefix":"10.1038","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8789-4585","authenticated-orcid":false,"given":"H\u00e9l\u00e8ne","family":"Martini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jodie","family":"Birch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7521-6955","authenticated-orcid":false,"given":"Francisco D. 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