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Skin aging from the perspective of dermal fibroblasts: the interplay between the adaptation to the extracellular matrix microenvironment and cell autonomous processes

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Journal of Cell Communication and Signaling Aims and scope

Abstract

This article summarizes important molecular mechanisms that drive aging in human skin from the perspective of dermal fibroblasts. The dermis comprises the bulk of the skin and is largely composed of a collagen‐rich extracellular matrix (ECM). The dermal ECM provides mechanical strength, resiliency, and an environment that supports the functions of ibroblasts and other types of dermal cells. Fibroblasts produce the dermal ECM and maintain its homeostasis. Fibroblasts attach to the ECM and this attachment controls their morphology and function. During aging, the ECM undergoes gradual degradation that is nitiated by matrix metalloproteinases (MMPs). This degradation alters mechanical forces within the dermal ECM and disrupts he interactions between fibroblasts and the ECM thereby generating an aged fibroblast phenotype. This aged fibroblast phenotype is characterized by collapsed morphology, altered mechanosignaling, induction of CCN1, and activation of transcription factor AP‐1, with consequent upregulation of target genes including MMPs and pro‐inflammatory mediators. The TGF‐beta pathway coordinately regulates ECM production and turnover. Altered mechanical forces, due to ECM fragmentation, down-regulate the type II TGF‐beta receptor, thereby reducing ECM production and further increasing ECM breakdown. Thus, dermal aging involves a feed‐forward process that reinforces the aged dermal fibroblast phenotype and promotes age‐related dermal ECM deterioration. As discussed in the article, the expression of the aged dermal fibroblast phenotype involves both adaptive and cell‐autonomous mechanisms.

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Acknowledgements

This work was supported by the National Institute of Health (AG054835 to GJ Fisher & T Quan; AG051849 to GJ Fisher & T Quan and P30AR075043 to Gudjonsson).

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Authors and Affiliations

  1. Department of Dermatology, University of Michigan, Ann Arbor, MI, USA

    Gary J. Fisher, Bo Wang, Yilei Cui, Mai Shi, Yi Zhao, Taihao Quan & John J. Voorhees

  2. Department of Dermatology, Tsinghua Changgung Hospital, Tsinghua University, Beijing, China

    Gary J. Fisher, Bo Wang, Yilei Cui, Mai Shi, Yi Zhao, Taihao Quan & John J. Voorhees

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  1. Gary J. Fisher
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Fisher, G.J., Wang, B., Cui, Y. et al. Skin aging from the perspective of dermal fibroblasts: the interplay between the adaptation to the extracellular matrix microenvironment and cell autonomous processes. J. Cell Commun. Signal. 17, 523–529 (2023). https://doi.org/10.1007/s12079-023-00743-0

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