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.

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Publication Details

Journal
Aging
Published
2024-09-23
DOI
https://doi.org/10.18632/aging.206117
Citations
7
Primary Topic
Telomeres, Telomerase, and Senescence
Type
article
Field-Weighted Citation Impact
2.29

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article

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

Caiyue Liu, Chen Wang, Qingfeng Li, Liang Zhang et al.
7 citations
Aging
Telomeres, Telomerase, and Senescence
2.29
article

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

Caiyue Liu, Chen Wang, Qingfeng Li, Liang Zhang, Dan Wu, Jianhua Lin, Lu-Wen Xu, Yidan Sun, Qiao-Yu Fu
article en
7 citations

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.

AgingVol. 16(18)
Shanghai Jiao Tong University (CN), Shanghai Institute of Nutrition and Health (CN), Shanghai Ninth People's Hospital (CN), Shanghai Changzheng Hospital (CN), Shanghai University of Medicine and Health Sciences (CN), University of Chinese Academy of Sciences (CN)
Natural Science Foundation of Shanghai, National Natural Science Foundation of China, China Postdoctoral Science Foundation, Science and Technology Commission of Shanghai Municipality, Shanghai Jiao Tong University, Shanghai Clinical Research Center, School of Medicine, Shanghai Jiao Tong University
Zero hunger
Openalex Percentile: Top 11%
Telomeres, Telomerase, and Senescence
2.29
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