{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:07:26Z","timestamp":1789016846487,"version":"build-2803163510"},"reference-count":126,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004704","name":"National Research Council of Thailand","doi-asserted-by":"crossref","award":["N42A680063"],"award-info":[{"award-number":["N42A680063"]}],"id":[{"id":"10.13039\/501100004704","id-type":"DOI","asserted-by":"crossref"}]},{"award":["N42A680063"],"award-info":[{"award-number":["N42A680063"]}],"id":[{"id":"https:\/\/ror.org\/018wfhg78","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Cellular senescence is one of the hallmarks of aging. These growth-arrested cells actively secrete inflammatory mediators that reshape the tissue microenvironment and fuel age-related pathology. Sirtuin 1 (SIRT1) is an NAD+-dependent deacetylase that regulates senescence largely through its control over mitochondrial integrity and inflammatory signaling. SIRT1 levels and activity fall with age, and this decline directly promotes senescence. SIRT1 maintains mitochondrial function through three interconnected pathways: PGC-1\u03b1-driven mitochondria biogenesis, FOXO-dependent antioxidant defense, and mitophagic clearance of damaged organelles. When SIRT1 activity is in an unsteady state, mitochondria become unhealthy. This leads to excessive ROS generation and the leakage of mitochondrial DNA (mtDNA) into the cytosol, which activates the innate immune pathway, consequently resulting in the production of inflammatory cytokines that further inhibit SIRT1. This self-amplifying loop drives cells to irreversible senescence. In this study, we integrate the current understanding of the SIRT1\u2013mitochondria\u2013immune axis within the framework of senescence by examining the biological roles of SIRT1 and the mechanisms that lead to its reduction with aging, while also exploring the interrelated mitochondrial pathways and inflammatory signaling. Furthermore, we assess possible therapeutic strategies targeting this axis and highlight essential questions that necessitate additional research.<\/jats:p>","DOI":"10.3390\/biology15181573","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T08:10:22Z","timestamp":1788855022000},"page":"1573","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["SIRT1 in Senescence: Mitochondria and Immune Crosstalk"],"prefix":"10.3390","volume":"15","author":[{"given":"Jirapat","family":"Namkaew","sequence":"first","affiliation":[{"name":"Futuristic Science Research Center, School of Science, Walailak University, Thasala, Nakhon Si Thammarat 80160, Thailand"},{"name":"Research Excellence Center for Innovation and Health Products (RECIHP), School of Allied Health Sciences, Walailak University, Thasala, Nakhon Si Thammarat 80160, Thailand"},{"name":"School of Science, Walailak University, Thasala, Nakhon Si Thammarat 80160, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1759-213X","authenticated-orcid":false,"given":"Pornparn","family":"Kongpracha","sequence":"additional","affiliation":[{"name":"Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA 94143, USA"},{"name":"Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA 94143, USA"},{"name":"Data Science and Biotechnology Institute, Gladstone Institutes, San Francisco, CA 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9406-8350","authenticated-orcid":false,"given":"Tanakamol","family":"Mahawan","sequence":"additional","affiliation":[{"name":"Akkhraratchakumari Veterinary College, Walailak University, Thasala, Nakhon Si Thammarat 80160, Thailand"},{"name":"One Health Research Centre, Walailak University, Thasala, Nakhon Si Thammarat 80160, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5222-7746","authenticated-orcid":false,"given":"Thiranut","family":"Jaroonwitchawan","sequence":"additional","affiliation":[{"name":"Futuristic Science Research Center, School of Science, Walailak University, Thasala, Nakhon Si Thammarat 80160, Thailand"},{"name":"Research Excellence Center for Innovation and Health Products (RECIHP), School of Allied Health Sciences, Walailak University, Thasala, Nakhon Si Thammarat 80160, Thailand"},{"name":"School of Science, Walailak University, Thasala, Nakhon Si Thammarat 80160, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1016\/j.cell.2013.05.039","article-title":"The hallmarks of aging","volume":"153","author":"Blasco","year":"2013","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1038\/s41392-022-01251-0","article-title":"Aging and aging-related diseases: From molecular mechanisms to interventions and treatments","volume":"7","author":"Guo","year":"2022","journal-title":"Signal Transduct. 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