Extracellular matrix regulation of fibroblast function: redefining our perspective on skin aging
Open accessAbstract
The dermal extracellular matrix (ECM) comprises the bulk of skin and confers strength and resiliency. In young skin, fibroblasts produce and adhere to the dermal ECM, which is composed primarily of type I collagen fibrils. Adherence allows fibroblasts to spread and exert mechanical force on the surrounding ECM. In this state, fibroblasts display a "youthful" phenotype characterized by maintenance of the composition and structural organization of the dermal ECM. During aging, fibroblast-ECM interactions become disrupted due to fragmentation of collagen fibrils. This disruption causes loss of fibroblast spreading and mechanical force, which inextricably lead to an "aged" phenotype; fibroblasts synthesize less ECM proteins and more matrix-degrading metalloproteinases. This imbalance of ECM homeostasis further drives collagen fibril fragmentation in a self-perpetuating cycle. This article summarizes age-related changes in the dermal ECM and the mechanisms by which these changes alter the interplay between fibroblasts and their extracellular matrix microenvironment that drive the aging process in human skin.
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Within the dermis of VSAs, Vimentin+ fibroblasts and Collagen I+ ECM were arranged directly beneath the epidermis.
“Within the dermis, Vimentin + fibroblasts and Collagen I + ECM were arranged directly beneath the epidermis, supporting dermal-epidermal compartmental organization, a structural feature relevant to human skin organization 26 (Fig. 3f, Supplementary Fig. 3c).”
From Vascularized human skin assembloids model compartmental skin organization and immune responsiveness in vitro (2026) · cites this paper as [26]
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References 77 · Cited by 365
- Authors
- Cole, M. A., Quan, T., Voorhees, J. J., & Fisher, G. J.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Fisher, Gary J.
- Venue
- Journal of Cell Communication and Signaling
- Publisher
- Wiley
- Published
- 2018-02-17
- Volume
- 12
- Issue
- 1
- Pages
- 35-43
- ISSN
- 1873-9601 (ISSN-L)
- 1873-961X
- PMC
- PMC5842211
- OpenAlex
- W2789947828
- Cited by
- 365
- References
- 77
- Citations by year
- 2026: 46 · 2025: 52 · 2024: 50 · 2023: 50 · 2022: 48 · 2021: 36 · 2020: 42 · 2019: 36 · 2018: 5
- FWCI
- 4.83
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Cell Communication and Signaling (publishedVersion, other-oa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG051849, AG054835)
- National Institutes of Health (T32-AM07197)
- Topics
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- skin aging, dermal extracellular matrix, fibroblasts, type I collagen fibrils, matrix metalloproteinases, fibroblast spreading, mechanical forces
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