Role of Age-Associated Alterations of the Dermal Extracellular Matrix Microenvironment in Human Skin Aging: A Mini-Review
Open accessAbstract
Human skin is largely composed of a collagen-rich connective tissue, which provides structural and functional support. The collagen-rich connective tissue is produced, organized, and maintained by dermal fibroblasts. During aging, dermal collagen fibrils undergo progressive loss and fragmentation, leading to thin and structurally weakened skin. Age-related alterations of collagen fibrils impairs skin structure and function and creates a tissue microenvironment that promotes age-related skin diseases, such as delayed wound healing and skin cancer development. This mini-review describes cellular mechanisms that give rise to self-perpetuating, collagen fibril fragmentation that creates an age-associated dermal microenvironment, which contributes to decline of human skin function.
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Skin aging changes are driven by intrinsic aging and extrinsic factors, particularly ultraviolet exposure, which promotes oxidative stress, chronic low-grade inflammation, and degradation of extracellular matrix components such as collagen and elastin.
“These changes are driven by intrinsic aging as well as extrinsic factors, particularly ultraviolet (UV) exposure, which promotes oxidative stress, chronic low-grade inflammation, and degradation of extracellular matrix components such as collagen and elastin [3,4,5].”
From A Randomized, Double-Blind, Placebo-Controlled Trial Assessing the Effects of Oral Centella asiatica Extract on Skin Aging-Related Parameters in Middle-Aged Korean Women. (2026) · cites this paper as [4]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredSkin wrinkle formation is a hallmark of both intrinsic aging and photoaging and is closely associated with collagen degradation and alterations in skin surface topography.
“Skin wrinkle formation is a hallmark of both intrinsic aging and photoaging and is closely associated with collagen degradation and alterations in skin surface topography [4,41,42].”
From A Randomized, Double-Blind, Placebo-Controlled Trial Assessing the Effects of Oral Centella asiatica Extract on Skin Aging-Related Parameters in Middle-Aged Korean Women. (2026) · cites this paper as [4]
The Introduction describes fine wrinkling in intrinsic aging and deep wrinkles in photoaging; it also describes collagen loss and fragmentation in aged skin. It does not specifically link wrinkle formation to collagen degradation or discuss changes in skin surface topography: its topographical images show dermal collagen fibrils, not the skin surface. No page numbers are available in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredHigh level of reactive oxygen species induces skin fibroblasts to secrete high levels of matrix metalloproteinases, which cause extensive extracellular matrix remodeling in dermal layers.
“High level of ROS was also reported to induce skin fibroblasts to secrete high levels of matrix metalloproteinases (MMPs), which caused extensive ECM remodeling in dermal layers [124–126].”
From Ultraviolet Radiation‐Induced Skin Aging: The Role of DNA Damage and Oxidative Stress in Epidermal Stem Cell Damage Mediated Skin Aging (2016) · cites this paper as [126]
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- Authors
- Quan, T., & Fisher, G. J.
- Affiliations
- University of Michigan (US)
- Venue
- Gerontology
- Publisher
- S. Karger AG
- Published
- 2015
- Volume
- 61
- Issue
- 5
- Pages
- 427-434
- ISSN
- 0304-324X (ISSN-L)
- 1423-0003
- PMC
- PMC4524793
- OpenAlex
- W4292189154
- Cited by
- 464
- References
- 48
- Citations by year
- 2026: 74 · 2025: 50 · 2024: 46 · 2023: 46 · 2022: 40 · 2021: 60 · 2020: 50 · 2019: 38 · 2018: 20 · 2017: 17 · 2016: 15 · 2015: 5
- FWCI
- 3.02
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gerontology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5r01ag031452-04, 5r01es014697-04, ES014697, AG031452, ES014697 30S1)
- National Institute on Aging (AG031452, R01-AG031452, AG025186, R01AG019364, R01AG025186, AG019364)
- National Institute of Environmental Health Sciences (R01-ES014697, ES014697 30S1, ES014697)
- Topics
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Physical Sciences › Materials Science › Biomaterials › Collagen: Extraction and Characterization
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Connective tissue disorders research
- Keywords
- skin aging, dermal extracellular matrix, collagen fibrils, dermal fibroblasts, delayed wound healing, skin cancer, collagen loss
- MeSH terms
- Aging, Connective Tissue, Extracellular Matrix, Humans, Models, Biological, Skin Diseases, Signal Transduction, Skin Aging, Transforming Growth Factor beta, Matrix Metalloproteinases, Cysteine-Rich Protein 61, Cellular Microenvironment
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