Lu-Wen Xu, Yi-Dan Sun, Qiao-Yu Fu, Dan Wu, Jian Lin, Chen Wang, Liang Zhang, Cai-Yue Liu, Qing-Feng Li
{"title":"揭示表皮老化过程中与衰老相关的分泌表型:可逆永生化角质形成细胞的启示","authors":"Lu-Wen Xu, Yi-Dan Sun, Qiao-Yu Fu, Dan Wu, Jian Lin, Chen Wang, Liang Zhang, Cai-Yue Liu, Qing-Feng Li","doi":"10.18632/aging.206117","DOIUrl":null,"url":null,"abstract":"<p><p>Aging of epidermal keratinocytes profoundly impacts skin health, contributing to changes in appearance, barrier function, and susceptibility to diseases. Despite its significance, the molecular mechanisms underlying epidermal aging remain elusive. In this study, a reversible immortalized cell line was established by expressing SV40T in keratinocytes using the Tet-Off lentiviral system. Inducing a senescent phenotype by terminating SV40T expression revealed a significant reduction in mitotic ability, as well as characteristics of cellular aging. RNA sequencing analysis revealed alterations in gene expression and signaling pathways including DNA repair dysfunction, notably senescence-associated secretory phenotype (SASP)-related genes, such as MMP1, SERPINB2 and VEGFA. Our study provides insights into the molecular mechanisms of epidermal aging, offering potential therapeutic targets and highlighting the role of SASP in the aging process.</p>","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":null,"pages":null},"PeriodicalIF":3.9000,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Unveiling senescence-associated secretory phenotype in epidermal aging: insights from reversibly immortalized keratinocytes.\",\"authors\":\"Lu-Wen Xu, Yi-Dan Sun, Qiao-Yu Fu, Dan Wu, Jian Lin, Chen Wang, Liang Zhang, Cai-Yue Liu, Qing-Feng Li\",\"doi\":\"10.18632/aging.206117\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Aging of epidermal keratinocytes profoundly impacts skin health, contributing to changes in appearance, barrier function, and susceptibility to diseases. Despite its significance, the molecular mechanisms underlying epidermal aging remain elusive. In this study, a reversible immortalized cell line was established by expressing SV40T in keratinocytes using the Tet-Off lentiviral system. Inducing a senescent phenotype by terminating SV40T expression revealed a significant reduction in mitotic ability, as well as characteristics of cellular aging. RNA sequencing analysis revealed alterations in gene expression and signaling pathways including DNA repair dysfunction, notably senescence-associated secretory phenotype (SASP)-related genes, such as MMP1, SERPINB2 and VEGFA. Our study provides insights into the molecular mechanisms of epidermal aging, offering potential therapeutic targets and highlighting the role of SASP in the aging process.</p>\",\"PeriodicalId\":55547,\"journal\":{\"name\":\"Aging-Us\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2024-09-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Aging-Us\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.18632/aging.206117\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Aging-Us","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.18632/aging.206117","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
Unveiling senescence-associated secretory phenotype in epidermal aging: insights from reversibly immortalized keratinocytes.
Aging of epidermal keratinocytes profoundly impacts skin health, contributing to changes in appearance, barrier function, and susceptibility to diseases. Despite its significance, the molecular mechanisms underlying epidermal aging remain elusive. In this study, a reversible immortalized cell line was established by expressing SV40T in keratinocytes using the Tet-Off lentiviral system. Inducing a senescent phenotype by terminating SV40T expression revealed a significant reduction in mitotic ability, as well as characteristics of cellular aging. RNA sequencing analysis revealed alterations in gene expression and signaling pathways including DNA repair dysfunction, notably senescence-associated secretory phenotype (SASP)-related genes, such as MMP1, SERPINB2 and VEGFA. Our study provides insights into the molecular mechanisms of epidermal aging, offering potential therapeutic targets and highlighting the role of SASP in the aging process.