The DOI matches its Crossref record; 45 of the 47 references it cites were found in a registry or an index.
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
“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
“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]
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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Citations
Cites
Oxidative Stress, Caloric Restriction, and Aging
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Pathophysiology of Premature Skin Aging Induced by Ultraviolet Light
Fisher, G. J., Wang, Z., Datta, S. C., Varani, J., Kang, S., & Voorhees, J. J. (1997) · New England Journal of Medicine · doi:10.1056/nejm199711133372003 · Cited by 1,501
Self-citationMolecular basis of sun-induced premature skin ageing and retinoid antagonism
Fisher, G. J., Datta, S. C., Talwar, H. S., Wang, Z.-Q., Varani, J., Kang, S., & Voorhees, J. J. (1996) · Nature · doi:10.1038/379335a0 · Cited by 1,410
Self-citationPhysiology, Biochemistry, and Molecular Biology of the Skin
Shelley, W. B. (1992) · JAMA · doi:10.1001/jama.1992.03490040129042 · Cited by 791
Topical tretinoin for photoaged skin
Kligman, A. M., Grove, G. L., Hirose, R., & Leyden, J. J. (1986) · Journal of the American Academy of Dermatology · doi:10.1016/s0190-9622(86)70242-9 · Cited by 620
Statistical Methods for the Analysis of Biomedical Data
Ziegel, E. R., & Woolson, R. F. (1989) · Technometrics · doi:10.2307/1268847 · Cited by 586
The estimation of two collagens from human dermis by interrupted gel electrophoresis
Sykes, B. C., Puddle, B., Francis, M. J. O., & Smith, R. (1976) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(76)80180-5 · Cited by 560
Topical Tretinoin Improves Photoaged Skin
Weiss, J. (1988) · JAMA · doi:10.1001/jama.1988.03720040019020 · Cited by 490
Restoration of Collagen Formation in Photodamaged Human Skin by Tretinoin (Retinoic Acid)
Griffiths, C. E. M., Russman, A., Majmudar, G., Singer, R. S., Hamilton, T. A., & Voorhees, J. J. (1993) · New England Journal of Medicine · doi:10.1056/nejm199308193290803 · Cited by 471
Structural Alterations in Exposed and Unexposed Aged Skin
Lavker, R. M. (1979) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12532763 · Cited by 464
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A tense situation: forcing tumour progression
Butcher, D. T., Alliston, T. N., & Weaver, V. M. (2009) · Nature reviews. Cancer · doi:10.1038/nrc2544 · Cited by 2,026
Mechanisms of photoaging and chronological skin aging
Fisher, G. J., Kang, S., Varani, J., Bata-Csorgo, Z., Wan, Y., Datta, S., & Voorhees, J. J. (2002) · Archives of Dermatology · doi:10.1001/archderm.138.11.1462 · Cited by 1,849
Self-citationTanaka, M., Yamamoto, Y., Misawa, E., Nabeshima, K., Saito, M., Yamauchi, K., Abe, F., & Furukawa, F. (2016) · Skin Pharmacology and Physiology · doi:10.1159/000454718 · Cited by 1,092
Decreased Collagen Production in Chronologically Aged Skin
Varani, J., Dame, M. K., Rittie, L., Fligiel, S. E. G., Kang, S., Fisher, G. J., & Voorhees, J. J. (2006) · The American Journal of Pathology · doi:10.2353/ajpath.2006.051302 · Cited by 910
Molecular Mechanisms of Dermal Aging and Antiaging Approaches
Shin, J.-W., Kwon, S.-H., Choi, J.-Y., Na, J.-I., Huh, C.-H., Choi, H.-R., & Park, K.-C. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20092126 · Cited by 875
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
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