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Updated: Jun 23, 2025

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Published on: February 17, 2021
Integrated bioinformatics analysis and experimental validation identifies CPE as a potential biomarker and
Xiaozhen Peng1,2,3, Yun Zhong1,3, Rui Mao1,3
1Hunan key laboratory of aging biology, Xiangya Hospital, Central South University, Changsha, China.
Abstract:
Ageing is an inevitable biological process characterized by progressive decline in physiological functions. It is a complex natural phenomenon that will cause structural and functional decline. Despite substantial progress in understanding the mechanism of ageing, both predictive biomarkers and preventive therapies remain limited. Using Weighted Gene Co-expression Network Analysis (WGCNA) and machine learning techniques, we identified Carboxypeptidase E (CPE) as a pivotal marker of skin ageing, based on ageing-related bulk transcriptome and single-cell transcriptome data. Next, our investigation reveals downregulation of CPE in replicative, UVA-induced, and H2O2-induced senescent human dermal fibroblast cells (HDFs). Furthermore, shRNA-mediated CPE knockdown induced HDFs senescence, and overexpression of CPE delayed HDFs senescence. Moreover, downregulated CPE inhibits collagen synthesis and induces inflammation, highlighting its potential as a therapeutic target for skin ageing. In conclusion, our study demonstrated that CPE functions as a predictor and optional target for therapeutic intervention of skin ageing.
Insights
Carboxypeptidase E (CPE) is identified as a key marker for skin aging. Lowering CPE accelerates skin aging, while increasing it delays aging, suggesting CPE as a therapeutic target.
Area of Science:
- Molecular Biology
- Dermatology
- Gerontology
Background:
- Aging is a natural process involving physiological decline, with limited predictive biomarkers and therapies.
- Understanding skin aging mechanisms is crucial for developing effective interventions.
Purpose of the Study:
- To identify pivotal biomarkers for skin aging using advanced computational techniques.
- To investigate the role of Carboxypeptidase E (CPE) in the aging process of human dermal fibroblasts.
Main Methods:
- Weighted Gene Co-expression Network Analysis (WGCNA) and machine learning on transcriptome data.
- Analysis of CPE expression in various induced senescence models of human dermal fibroblasts (HDFs).
- Experimental manipulation of CPE levels (knockdown and overexpression) in HDFs.
Main Results:
- Carboxypeptidase E (CPE) was identified as a pivotal marker of skin aging.
- CPE expression is downregulated in senescent HDFs (replicative, UVA, and H2O2-induced).
- CPE knockdown accelerates HDF senescence; CPE overexpression delays it, inhibiting collagen loss and inflammation.
Conclusions:
- CPE acts as a significant predictor of skin aging.
- CPE demonstrates potential as a therapeutic target for mitigating skin aging.
- Modulating CPE levels offers a novel strategy for skin aging intervention.
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