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Cellular senescence is associated with skin aging, and identification of specific markers of senescent cells is essential for development of targeted therapies. Cathepsin F (CTSF) has been implicated in dermatitis and various cancers and participates in cell immortalization through its association with Bcl family proteins. It is a candidate therapeutic target to specifically label and eliminate human skin fibroblasts and keratinocytes immortalized by aging and achieve skin rejuvenation. In this study, we investigated whether CTSF is associated with senescence in human fibroblasts and keratinocytes. In senescence models, created using replicative aging, ionizing radiation exposure, and the anticancer drug doxorubicin, various senescence markers were observed, such as senescence-associated \u03b2-galactosidase (SA-\u03b2-gal) activity, increased SASP gene expression, and decreased uptake of the proliferation marker BrdU. Furthermore, CTSF expression was elevated at the gene and protein levels. In addition, CTSF-positive cells were abundant in aged human epidermis and in some parts of the dermis. In the population of senescent cells with arrested division, the number of CTSF-positive cells was significantly higher than that in the proliferating cell population. These results suggest that CTSF is a candidate for therapeutic modalities targeting aging fibroblasts and keratinocytes.<\/jats:p>","DOI":"10.1007\/s11357-022-00648-7","type":"journal-article","created":{"date-parts":[[2022,9,3]],"date-time":"2022-09-03T04:02:45Z","timestamp":1662177765000},"page":"427-437","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Cathepsin F is a potential marker for senescent human skin fibroblasts and keratinocytes associated with skin aging"],"prefix":"10.1007","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8992-2762","authenticated-orcid":false,"given":"Kento","family":"Takaya","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9312-3584","authenticated-orcid":false,"given":"Toru","family":"Asou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4298-9828","authenticated-orcid":false,"given":"Kazuo","family":"Kishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,9,3]]},"reference":[{"key":"648_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.10.005","author":"V Gorgoulis","year":"2019","unstructured":"Gorgoulis V, Adams PD, Alimonti A, Bennett DC, Bischof O, Bishop C, et al. 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