Research Paper Volume 16, Issue 18 pp 12651—12666
Unveiling senescence-associated secretory phenotype in epidermal aging: insights from reversibly immortalized keratinocytes
- 1 Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200021, China
- 2 Department of Plastic and Reconstructive Surgery, Changzheng Hospital, Naval Medical University, Shanghai 200003, China
- 3 Department of Center for Orthopedic Repair and Reconstruction, Chongming Hospital Affiliated to Shanghai University of Medicine and Health Sciences, Shanghai 202150, China
- 4 CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031 China
- 5 Shanghai Key Laboratory of Reproductive Medicine, Shanghai, China
Received: February 10, 2024 Accepted: July 16, 2024 Published: September 23, 2024
https://doi.org/10.18632/aging.206117How to Cite
Copyright: © 2024 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
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.
Abbreviations
β-GAL: beta-galactosidase; DEGs: differentially-expressed genes; Dox: doxycycline; GSEA: gene set enrichment analysis; GO: gene ontology; H2A.X: H2A histone family member X; IFN: interferon; IGFBP: insulin-like growth factor-binding protein; IL: interleukin; JAK: Janus kinase; KEGG: Kyoto Encyclopedia of Genes and Genomes; KRAS: Kirsten rat sarcoma virus; MMP: matrix metalloproteinases; NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells; NHDF: normal human dermal fibroblast; NHEK: normal human epidermal keratinocyte; Rb: retinoblastoma protein; SASP: senescence-associated secretory phenotype; SERPIN: serine protease inhibitors; STAT: signal transducer and activator of transcription; TGF: transforming growth factor; VEGFA: vascular endothelial growth factor A.