Cited by 643Skin Protection and AgingProtease and Inhibitor MechanismsDermatologic Treatments and Research

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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

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Varani, James, Warner, Roscoe L., Gharaee-Kermani, Mehrnaz, Phan, Sem H., Kang, Sewon, Chung, JinHo, Wang, ZengQuan, Datta, Subhash C., Fisher, Gary J., Voorhees, John J.·2000·Journal of Investigative Dermatology

DOI 10.1046/j.1523-1747.2000.00902.x

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Abstract

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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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
ORCID: Phan, Sem H.
Kang, Sewon
Wang, ZengQuan
Fisher, Gary J.
Venue: Journal of Investigative Dermatology
Publisher: Elsevier BV
Published: 2000-03
Volume: 114
Issue: 3
Pages: 480-486
ISSN: 0022-202X (ISSN-L)
DOI: 10.1046/j.1523-1747.2000.00902.x
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 5754 d)
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

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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

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