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This review examines mitochondrial dysfunction as a mechanistic bridge linking bioenergetic failure to cellular senescence and inflammaging, two central features of biological ageing. We discuss how impaired oxidative phosphorylation, loss of mitochondrial membrane potential, increased electron leak, and excessive reactive oxygen species progressively damage mitochondrial DNA, proteins, and lipids, thereby amplifying organelle dysfunction and compromising cellular homeostasis. Particular emphasis is placed on the threshold effect of mitochondrial DNA mutations, whose age-dependent clonal expansion can drive respiratory chain deficiency in vulnerable tissues. We further analyze mitochondria as signalling platforms that integrate regulated cell death, including apoptosis, necroptosis, pyroptosis, and ferroptosis, and as sources of mitochondrial damage-associated molecular patterns promoting sterile inflammation. Finally, we highlight mitochondrial dysfunction-associated senescence as a central process through which persistent mitochondrial stress reshapes the senescence-associated secretory phenotype and reinforces inflammaging. Overall, the evidence supports a model in which dysfunctional mitochondria act as both initiators and amplifiers of senescence and inflammation, contributing to tissue degeneration and age-related functional decline. Understanding these interconnected mechanisms may help identify therapeutic strategies targeting mitochondrial bioenergetics, inflammatory signalling, and senescent cell burden in ageing.<\/jats:p>","DOI":"10.1007\/s11357-026-02588-y","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T21:59:43Z","timestamp":1791583183000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mitochondrial dysfunction and inflammaging: a mechanistic bridge between bioenergetic failure and senescence"],"prefix":"10.1007","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8569-7158","authenticated-orcid":false,"given":"Salvatore","family":"Nesci","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Algieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,9]]},"reference":[{"key":"2588_CR1","doi-asserted-by":"publisher","first-page":"401","DOI":"10.3390\/life12030401","volume":"12","author":"C Garone","year":"2022","unstructured":"Garone C, Pietra A, Nesci S. 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