{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:10:34Z","timestamp":1791389434651,"version":"4.3.3"},"reference-count":46,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T00:00:00Z","timestamp":1697155200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT, South Korea","doi-asserted-by":"publisher","award":["2019R1F1A1059005"],"award-info":[{"award-number":["2019R1F1A1059005"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004332","name":"Seoul National University Hospital","doi-asserted-by":"publisher","award":["04\u20102016\u20100250"],"award-info":[{"award-number":["04\u20102016\u20100250"]}],"id":[{"id":"10.13039\/501100004332","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Aging is accompanied by impaired mitochondrial function and accumulation of senescent cells. Mitochondrial dysfunction contributes to senescence by increasing the levels of reactive oxygen species and compromising energy metabolism. Senescent cells secrete a senescence\u2010associated secretory phenotype (SASP) and stimulate chronic low\u2010grade inflammation, ultimately inducing inflammaging. Mitochondrial dysfunction and cellular senescence are two closely related hallmarks of aging; however, the key driver genes that link mitochondrial dysfunction and cellular senescence remain unclear. Here, we aimed to elucidate a novel role of carnitine acetyltransferase (CRAT) in the development of mitochondrial dysfunction and cellular senescence in dermal fibroblasts. Transcriptomic analysis of skin tissues from young and aged participants showed significantly decreased CRAT expression in intrinsically aged skin. CRAT downregulation in human dermal fibroblasts recapitulated mitochondrial changes in senescent cells and induced SASP secretion. Specifically, CRAT knockdown caused mitochondrial dysfunction, as indicated by increased oxidative stress, disruption of mitochondrial morphology, and a metabolic shift from oxidative phosphorylation to glycolysis. Mitochondrial damage induced the release of mitochondrial DNA into the cytosol, which activated the cyclic GMP\u2010AMP synthase (cGAS)\u2010stimulator of interferon genes (STING) and NF\u2010\u0138B pathways to induce SASPs. Consistently, fibroblast\u2010specific CRAT\u2010knockout mice showed increased skin aging phenotypes in vivo, including decreased cell proliferation, increased SASP expression, increased inflammation, and decreased collagen density. Our results suggest that CRAT deficiency contributes to aging by mediating mitochondrial dysfunction\u2010induced senescence.<\/jats:p>","DOI":"10.1111\/acel.14000","type":"journal-article","created":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T03:41:02Z","timestamp":1697168462000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Carnitine acetyltransferase deficiency mediates mitochondrial dysfunction\u2010induced cellular senescence in dermal fibroblasts"],"prefix":"10.1111","volume":"22","author":[{"given":"Min Ji","family":"Song","sequence":"first","affiliation":[{"name":"Department of Dermatology Seoul National University College of Medicine  Seoul Republic of Korea"},{"name":"Department of Biomedical Sciences Seoul National University Graduate School  Seoul Republic of Korea"},{"name":"Institute of Human\u2010Environment Interface Biology, Medical Research Center, Seoul National University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi\u2010Hyun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Dermatology Seoul National University College of Medicine  Seoul Republic of Korea"},{"name":"Institute of Human\u2010Environment Interface Biology, Medical Research Center, Seoul National University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haesoo","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Dermatology Seoul National University College of Medicine  Seoul Republic of Korea"},{"name":"Department of Biomedical Sciences Seoul National University Graduate School  Seoul Republic of Korea"},{"name":"Institute of Human\u2010Environment Interface Biology, Medical Research Center, Seoul National University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sangbum","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences Seoul National University Graduate School  Seoul Republic of Korea"},{"name":"Institute of Human\u2010Environment Interface Biology, Medical Research Center, Seoul National University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si Hyung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Dermatology Seoul National University College of Medicine  Seoul Republic of Korea"},{"name":"Institute of Human\u2010Environment Interface Biology, Medical Research Center, Seoul National University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2925-3074","authenticated-orcid":false,"given":"Dong Hun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Dermatology Seoul National University College of Medicine  Seoul Republic of Korea"},{"name":"Institute of Human\u2010Environment Interface Biology, Medical Research Center, Seoul National University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0582-6392","authenticated-orcid":false,"given":"Jin Ho","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Dermatology Seoul National University College of Medicine  Seoul Republic of Korea"},{"name":"Department of Biomedical Sciences Seoul National University Graduate School  Seoul Republic of Korea"},{"name":"Institute of Human\u2010Environment Interface Biology, Medical Research Center, Seoul National University  Seoul Republic of Korea"},{"name":"Institute on Aging, Seoul National University  Seoul Republic of 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