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Vitamin A Antagonizes Decreased Cell Growth and Elevated Collagen-Degrading Matrix Metalloproteinases and Stimulates Collagen Accumulation in Naturally Aged Human Skin1
Open accessAbstract
Damage to human skin due to ultraviolet light from the sun (photoaging) and damage occurring as a consequence of the passage of time (chronologic or natural aging) are considered to be distinct entities. Photoaging is caused in part by damage to skin connective tissue by increased elaboration of collagen-degrading matrix metalloproteinases, and by reduced collagen synthesis. As matrix metalloproteinase levels are known to rise in fibroblasts as a function of age, and as oxidant stress is believed to underlie changes associated with both photoaging and natural aging, we determined whether natural skin aging, like photoaging, gives rise to increased matrix metalloproteinases and reduced collagen synthesis. In addition, we determined whether topical vitamin A (retinol) could stimulate new collagen deposition in sun-protected aged skin, as it does in photoaged skin. Sun-protected skin samples were obtained from 72 individuals in four age groups: 18-29 y, 30-59 y, 60-79 y, and 80+ y. Histologic and cellular markers of connective tissue abnormalities were significantly elevated in the 60-79 y and 80+ y groups, compared with the two younger age groups. Increased matrix metalloproteinase levels and decreased collagen synthesis/expression were associated with this connective tissue damage. In a separate group of 53 individuals (80+ y of age), topical application of 1% vitamin A for 7 d increased fibroblast growth and collagen synthesis, and concomitantly reduced the levels of matrix-degrading matrix metalloproteinases. Our findings indicate that naturally aged, sun-protected skin and photoaged skin share important molecular features including connective tissue damage, elevated matrix metalloproteinase levels, and reduced collagen production. In addition, vitamin A treatment reduces matrix metalloproteinase expression and stimulates collagen synthesis in naturally aged, sun-protected skin, as it does in photoaged skin.
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In the citing paper
“Retinoids and all biologically active forms of vitamin A also promote the remodeling of reticulin fibers and synthesis of a new capillary network in the dermis.”
From Bioactive Compounds for Skin Health: A Review (2021) · cites this paper as [42]
Experimental — accuracy not yet measuredIn the citing paper
“This process influences the condition of the connective tissue of the dermis, improving its firmness, hydration and elasticity [35,42].”
From Bioactive Compounds for Skin Health: A Review (2021) · cites this paper as [42]
In the citing paper
“After penetrating the dermis, retinoids increase the synthesis of elastin and collagen by stimulating the fibroblasts [42].”
From Bioactive Compounds for Skin Health: A Review (2021) · cites this paper as [42]
In the citing paper
“Retinoids protect collagen against the destruction induced by MMPs, as well as enhancing the synthesis of tissue inhibitors of metalloproteinases (TIMPs) [32,42].”
From Bioactive Compounds for Skin Health: A Review (2021) · cites this paper as [42]
In the citing paper
“Varani et al. observed that topical vitamin A (retinol) reduced MMP expression and increased fibroblast growth and collagen synthesis in naturally aged, as it did in photoaged, skin [42].”
From Bioactive Compounds for Skin Health: A Review (2021) · cites this paper as [42]
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Metadata
- Authors
- Varani, J., Warner, R. L., Gharaee-Kermani, M., Phan, S. H., Kang, S., Chung, J., Wang, Z., Datta, S. C., Fisher, G. J., & Voorhees, J. J.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Varani, James
- Venue
- Journal of Investigative Dermatology
- Publisher
- Elsevier BV
- Published
- 2000-03
- Volume
- 114
- Issue
- 3
- Pages
- 480-486
- ISSN
- 0022-202X (ISSN-L)
- OpenAlex
- W2077292033
- Cited by
- 643
- References
- 47
- Citations by year
- 2026: 19 · 2025: 30 · 2024: 25 · 2023: 24 · 2022: 22 · 2021: 27 · 2020: 17 · 2019: 29 · 2018: 18 · 2017: 31 · 2016: 35 · 2015: 34 · 2014: 27 · 2013: 25 · 2012: 22
- FWCI
- 15.16
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Investigative Dermatology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Health Sciences › Medicine › Dermatology › Dermatologic Treatments and Research
- Keywords
- photoaging, vitamin A, retinol, matrix metalloproteinases, collagen synthesis, collagen deposition, fibroblast proliferation, connective tissue damage, sun-protected skin, oxidative stress
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Aging, Cell Division, Collagen, Connective Tissue, Fibroblasts, Humans, Middle Aged, Procollagen, Skin, Stimulation, Chemical, Vitamin A, Skin Aging, Matrix Metalloproteinases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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