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Research Paper|Volume 16, Issue 18|pp 12651—12666

Unveiling senescence-associated secretory phenotype in epidermal aging: insights from reversibly immortalized keratinocytes

Lu-Wen Xu1, Yi-Dan Sun1, Qiao-Yu Fu1, Dan Wu2, Jian Lin3, Chen Wang1, Liang Zhang4,5, Cai-Yue Liu1, Qing-Feng Li1
  • 1Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200021, China
  • 2Department of Plastic and Reconstructive Surgery, Changzheng Hospital, Naval Medical University, Shanghai 200003, China
  • 3Department of Center for Orthopedic Repair and Reconstruction, Chongming Hospital Affiliated to Shanghai University of Medicine and Health Sciences, Shanghai 202150, China
  • 4CAS 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
  • 5Shanghai Key Laboratory of Reproductive Medicine, Shanghai, China
* Co-author
Received: February 10, 2024Accepted: July 16, 2024Published: September 23, 2024
https://doi.org/10.18632/aging.206117

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.