Pathway-level insights into the epigenetic ageing of human skin.

Skin ageing emerges from the interplay of intrinsic biological decline, environmental exposures and disease-related remodelling, yet the pathway-level epigenetic programs that integrate these processes remain largely unresolved. Here, we develop a skin-specific PathwayAge clock that aggregates DNA m...

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Published in:Age & Ageing Vol. 55; no. 4; pp. 1 - 11
Main Authors: Jiang, Jindou, Li, Pan, Zhu, Jijun, Cai, Fuqiang, Wang, Shenghan, Huang, Zhongting, Zhang, Shunjie, Zhou, Fusheng, Zhong, Wenwei, Chen, Junfang
Format: Article
Published: Oxford University Press / USA Apr2026
Subjects:
Online Access:View this record in EBSCOhost
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      dt: Apr2026
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        10.1093/ageing/afag118
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        atl: Pathway-level insights into the epigenetic ageing of human skin.
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        au:
          Jiang, Jindou
          Li, Pan
          Zhu, Jijun
          Cai, Fuqiang
          Wang, Shenghan
          Huang, Zhongting
          Zhang, Shunjie
          Zhou, Fusheng
          Zhong, Wenwei
          Chen, Junfang
        affil:
          Department of Aesthetic Medicine Guangdong Women and Children Hospital, Guangzhou Medicine University, Guanzhou, China
          School of Life Sciences, Fudan University, Shanghai, China
          The Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital), Guangzhou, China
          School of Biology and Biological Engineering, South China University of Technology, Guangzhou, China
          Center for Intelligent Medicine, Greater Bay Area Institute of Precision Medicine (Guangzhou), Guangzhou, China
          Department of Dermatology, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, Anhui, ChinaInstitute of Dermatology, Anhui Medical University, Hefei 230032, Anhui, ChinaKey Laboratory of Dermatology, Anhui Medical University, Ministry of Education, Hefei 230032, Anhui, China
          Faculty of Chinese Medicine, Macau University of Science and Technology, Taipa, Macao
          Center for Intelligent Medicine Area Institute of Precision Medicine (Guangzhou), Fudan University, Shanghai 200433, ChinaCenter for Evolutionary Biology, Fudan University, Shanghai 200433, China
      su:
        Case-control method
        Genome-wide association studies
        Research funding
        Epigenomics
        Logistic regression analysis
        Mann Whitney U Test
        DNA methylation
        Machine learning
        Skin aging
        Overall survival
        Proportional hazards models
        Evaluation
      sug:
        subj:
          Case-control method
          Genome-wide association studies
          Research funding
          Epigenomics
          Logistic regression analysis
          Mann Whitney U Test
          DNA methylation
          Machine learning
          Skin aging
          Overall survival
          Proportional hazards models
          Evaluation
      keyword:
        aging
        copyrightHolder:British Geriatrics Society
        copyrightYear:2026
        dna methylation
        epigenetic clock
        epigenetics
        https://dx.doi.org/10.1093/ageing/afag118
        inflammation
        inLanguage:en
        PathwayAge
        photoageing
        publisher:Oxford University Press
        sameAs:https://pubmed.ncbi.nlm.nih.gov/42051143/
        skin
        skin ageing
        skin aging
        solar degeneration
        aging
        copyrightHolder:British Geriatrics Society
        copyrightYear:2026
        dna methylation
        epigenetic clock
        epigenetics
        https://dx.doi.org/10.1093/ageing/afag118
        inflammation
        inLanguage:en
        PathwayAge
        photoageing
        publisher:Oxford University Press
        sameAs:https://pubmed.ncbi.nlm.nih.gov/42051143/
        skin
        skin ageing
        skin aging
        solar degeneration
      ab: Skin ageing emerges from the interplay of intrinsic biological decline, environmental exposures and disease-related remodelling, yet the pathway-level epigenetic programs that integrate these processes remain largely unresolved. Here, we develop a skin-specific PathwayAge clock that aggregates DNA methylation into biologically interpretable gene ontology pathways, enabling both precise quantification of epigenetic age and mechanistic dissection of cutaneous ageing. The model demonstrates high accuracy and strong generalisability across multiple independent cohorts, providing a robust foundation for mapping pathway-level ageing biology in human skin. Comprehensive analyses reveal four core functional modules underlying skin epigenetic ageing, encompassing cellular process, stress and immune responses, developmental process, and signal and regulation. These programs show substantial concordance with systemic ageing pathways in blood, indicating shared epigenetic architecture across tissues. Sun-exposed skin exhibits pronounced age acceleration driven by oxidative stress, inflammatory activation and metabolic perturbation, defining the molecular signature of photoageing. In disease settings, actinic keratosis and squamous cell carcinoma display marked ageing acceleration with proliferative and extracellular matrix dysregulation; melanoma progression involves coordinated remodelling of stress, immune, structural and metabolic ageing programs; and psoriasis demonstrates inflammation- and differentiation-driven premature ageing. Together, these findings position the skin-specific PathwayAge clock as a mechanistic and quantitative framework for decoding intrinsic ageing, photoageing and disease-associated remodelling. This work advances a unified understanding of cutaneous ageing biology and provides a foundation for precision assessment and targeted intervention in skin ageing.
      pubtype: Academic Journal
      doctype: Article
      src: R
    language: English
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