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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
This process influences the condition of the connective tissue of the dermis, improving its firmness, hydration and elasticity.
“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]
Retinoids and all biologically active forms of vitamin A promote remodeling of reticulin fibers and synthesis of a new capillary network in the dermis.
“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]
After penetrating the dermis, retinoids increase the synthesis of elastin and collagen by stimulating fibroblasts.
“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]
Retinoids protect collagen against destruction induced by MMPs and enhance synthesis of tissue inhibitors of metalloproteinases (TIMPs).
“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]
Topical vitamin A (retinol) reduced MMP expression and increased fibroblast growth and collagen synthesis in naturally aged, as it did in photoaged, skin.
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Oxidative Stress, Caloric Restriction, and Aging
Sohal, R. S., & Weindruch, R. H. (1996) · Science · doi:10.1126/science.273.5271.59 · Cited by 3,133 · see citing works
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 · see citing works
Molecular 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 · see citing works
Self-citationPhysiology, Biochemistry, and Molecular Biology of the Skin
Shelley, W. B. (1992) · JAMA · doi:10.1001/jama.1992.03490040129042 · Cited by 791 · see citing works
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 · see citing works
Statistical Methods for the Analysis of Biomedical Data
Ziegel, E. R., & Woolson, R. F. (1989) · Technometrics · doi:10.2307/1268847 · Cited by 582 · see citing works
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 · see citing works
Topical Tretinoin Improves Photoaged Skin
Weiss, J. (1988) · JAMA · doi:10.1001/jama.1988.03720040019020 · Cited by 490 · see citing works
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 · see citing works
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 · see citing works
Reduced Type I and Type III Procollagens in Photodamaged Adult Human Skin
Talwar, H. S., Griffiths, C. E. M., Fisher, G. J., Hamilton, T. A., & Voorhees, J. J. (1995) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12318471 · Cited by 400 · see citing works
Early Destructive Effect of Sunlight on Human Skin
Kligman, A. M. (1969) · JAMA · doi:10.1001/jama.1969.03160390039008 · Cited by 389 · see citing works
Key, G., Becker, M., Baron, B., Duchrow, M., Schlüter, C., Flad, H. D., & Gerdes, J. (1993) · PubMed · Cited by 376 · see citing works
Kang, S., Duell, E. A., Fisher, G. J., Datta, S. C., Wang, Z.-Q., Reddy, A. P., Tavakkol, A., Yi, J. Y., Griffiths, C. E. M., Elder, J. T., et al. (1995) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12323445 · Cited by 330 · see citing works
Statistical Methods for the Analysis of Biomedical Data.
Elton, R. A., & Woolson, R. F. (1988) · Journal of the Royal Statistical Society Series A (Statistics in Society) · doi:10.2307/2983034 · Cited by 300 · see citing works
Type I and III collagen content and fibre distribution in normal human skin during ageing
Lovell, C. R., Smolenski, K. A., Duance, V. C., Light, N. D., Young, S. R., & DYSON, M. L. (1987) · British Journal of Dermatology · doi:10.1111/j.1365-2133.1987.tb04921.x · Cited by 299 · see citing works
Alterations in Human Dermal Connective Tissue with Age and Chronic Sun Damage
Smith, J. G., Davidson, E. A., SAMS, W. M., & Clark, R. D. (1962) · Journal of Investigative Dermatology · doi:10.1038/jid.1962.122 · Cited by 293 · see citing works
West, M. D., Pereira‐Smith, O. M., & Smith, J. R. (1989) · Experimental Cell Research · doi:10.1016/0014-4827(89)90372-8 · Cited by 242 · see citing works
Millis, A. J. T., Hoyle, M., McCue, H. M., & Martini, H. (1992) · Experimental Cell Research · doi:10.1016/0014-4827(92)90286-h · Cited by 239 · see citing works
Brenneisen, P., Wenk, J., Klotz, L., Wlaschek, M., Briviba, K., Krieg, T., Sies, H., & Scharffetter‐Kochanek, K. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.9.5279 · Cited by 223 · see citing works
Ricciarelli, R., Maroni, P., Özer, N. K., Zingg, J.-M., & Azzi, A. (1999) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(99)00007-6 · Cited by 180 · see citing works
In Vitro Assessment of Keratinocyte Aging
Gilchrest, B. A. (1983) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12541084 · Cited by 160 · see citing works
The cellular and molecular biology of skin aging.
West, M. D. (1994) · PubMed · Cited by 130 · see citing works
Elastin Production in Human Skin Fibroblast Cultures and Its Decline with Age
Sephel, G. C., & Davidson, J. M. (1986) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12285424 · Cited by 117 · see citing works
Effects of topical tretinoin on non-sun-exposed protected skin of the elderly
Kligman, A. M., Dogadkina, D., & Lavker, R. M. (1993) · Journal of the American Academy of Dermatology · doi:10.1016/0190-9622(93)70147-l · Cited by 112 · see citing works
The Cellular and Molecular Biology of Skin Aging
West, M. D. (1994) · Archives of Dermatology · doi:10.1001/archderm.1994.01690010091014 · Cited by 107 · see citing works
Sauder, D. N., Stanulis‐Praeger, B. M., & Gilchrest, B. A. (1988) · Archives of Dermatological Research · doi:10.1007/bf00417707 · Cited by 106 · see citing works
Varani, J., Perone, P., Griffiths, C. E. M., Inman, D. R., Fligiel, S., & Voorhees, J. J. (1994) · Journal of Clinical Investigation · doi:10.1172/jci117522 · Cited by 105 · see citing works
Growth Factor Responsiveness of Cultured Human Fibroblasts Declines with Age
Plisko, A., & Gilchrest, B. A. (1983) · Journal of Gerontology · doi:10.1093/geronj/38.5.513 · Cited by 102 · see citing works
Growth factor responsiveness declines during adulthood for human skin-derived cells
Stanulis-Praeger, B., & Gilchrest, B. A. (1986) · Mechanisms of Ageing and Development · doi:10.1016/0047-6374(86)90009-6 · Cited by 96 · see citing works
Varani, J., Mitra, R. S., Gibbs, D. F., Phan, S. H., Dixit, V. M., Mitra, R., Wang, T., Siebert, K. J., Nickoloff, B. J., & Voorhees, J. J. (1990) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12876294 · Cited by 87 · see citing works
Mulligan, M. S., Desrochers, P. E., Chinnaiyan, A. M., Gibbs, D. F., Varani, J., Johnson, K. J., & Weiss, S. J. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.24.11523 · Cited by 81 · see citing works
Effects of donor age on protein and collagen synthesis in vitro by human diploid fibroblasts.
Bd, J., Rc, P., Narayanan, A. S., & Hp, P. (1986) · PubMed · Cited by 59 · see citing works
A new assay for collagenolytic activity
Hu, C., Crombie, G., & Franzblau, C. (1978) · Analytical Biochemistry · doi:10.1016/0003-2697(78)90467-0 · Cited by 56 · see citing works
Burke, E. M., Horton, W. E., Pearson, J. D., Crow, M. T., & Martin, G. R. (1994) · Experimental Gerontology · doi:10.1016/0531-5565(94)90061-2 · Cited by 50 · see citing works
The Steady-state Levels of Type I Collagen mRNA Are Reduced in Senescent Fibroblasts
Fürth, J. (1991) · Journal of Gerontology · doi:10.1093/geronj/46.3.b122 · Cited by 50 · see citing works
Miyahara, T., Murai, A., Tanaka, T., Shiozawa, S., & Kameyama, M. (1982) · Journal of Gerontology · doi:10.1093/geronj/37.6.651 · Cited by 49 · see citing works
Collagenase production by early and late passage cultures of human fibroblasts
Millis, A. J. T., Sottile, J., Hoyle, M., Mann, D. M., & Diemer, V. (1989) · Experimental Gerontology · doi:10.1016/0531-5565(89)90060-0 · Cited by 48 · see citing works
Bizot‐Foulon, V., Bouchard, B., Hornebeck, W., Dubertret, L., & Bertaux, B. (1995) · Cell Biology International · doi:10.1006/cbir.1995.1053 · Cited by 46 · see citing works
Murata, J., Ayukawa, K., Ogasawara, M., Fujii, H., & SAIKI, I. (1997) · PubMed · Cited by 38 · see citing works
The separation of two soft‐tissue collagens by covalent chromatography
Sykes, B. C. (1976) · FEBS Letters · doi:10.1016/0014-5793(76)81032-0 · Cited by 35 · see citing works
Varani, J., Larson, B. K., Perone, P., Inman, D. R., Fligiel, S., & Voorhees, J. J. (1993) · PubMed Central · Cited by 26 · see citing works
人の皮膚コラーゲンにおける年齢関連差異-溶液中の溶解性、ペプシン消化に対する感受性、および可溶化ポリメリックコラーゲン分子のスペクトル
Miyahara, T., Murai, A., Tanaka, T., Shiozawa, S., & Kameyama, M. (1982) · The Journals of Gerontology Series A · Cited by 26 · see citing works
Mays, P. K., McAnulty, R. J., Campa, J. S., Cambrey, A. D., & Laurent, G. J. (1990) · Biochemical Society Transactions · doi:10.1042/bst0180957 · Cited by 10 · see citing works
Varani, J., Perone, P., Fligiel, S., Inman, D. R., & Voorhees, J. J. (1994) · Archives of Dermatological Research · doi:10.1007/bf00371569 · Cited by 8 · see citing works
Flagged first, then by citations
2 of the 47 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
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 1,922 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
Ganceviciene, R., Liakou, A. I., Theodoridis, A., Makrantonaki, E., & Zouboulis, C. C. (2012) · Dermato-Endocrinology · doi:10.4161/derm.22804 · Cited by 844 · see citing works
Baumann, L. (2007) · The Journal of Pathology · doi:10.1002/path.2098 · Cited by 675 · see citing works
Natural and Sun-Induced Aging of Human Skin
Rittie, L., & Fisher, G. J. (2015) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a015370 · Cited by 600 · see citing works
Retinoids in the treatment of skin aging: an overview of clinical efficacy and safety
Mukherjee, S., Date, A., Patravale, V., Korting, H. C., Roeder, A., & Weindl, G. (2006) · Clinical Interventions in Aging · doi:10.2147/ciia.2006.1.4.327 · Cited by 580 · see citing works
Looking Older: Fibroblast Collapse and Therapeutic Implications
Fisher, G. J., Varani, J., & Voorhees, J. J. (2008) · Archives of Dermatology · doi:10.1001/archderm.144.5.666 · Cited by 540 · see citing works
Huang, Z.-R., Lin, Y., & Fang, J. (2009) · Molecules · doi:10.3390/molecules14010540 · Cited by 492 · see citing works
Fisher, G. J., Quan, T., Purohit, T., Shao, Y., Cho, M. K., He, T., Varani, J., Kang, S., & Voorhees, J. J. (2009) · The American Journal of Pathology · doi:10.2353/ajpath.2009.080599 · Cited by 487 · see citing works
Modulation of Skin Collagen Metabolism in Aged and Photoaged Human Skin In Vivo
Chung, J. H., Seo, J. Y., Choi, H. R., Lee, M. K., Youn, C. S., Rhie, G., Cho, K. H., Kim, K. H., Park, K. C., & Eun, H. C. (2001) · Journal of Investigative Dermatology · doi:10.1046/j.0022-202x.2001.01544.x · Cited by 410 · see citing works
Extracellular matrix regulation of fibroblast function: redefining our perspective on skin aging
Cole, M. A., Quan, T., Voorhees, J. J., & Fisher, G. J. (2018) · Journal of Cell Communication and Signaling · doi:10.1007/s12079-018-0459-1 · Cited by 365 · see citing works
Bioactive Compounds for Skin Health: A Review
Michalak, M., Pierzak, M., Kręcisz, B., & Suliga, E. (2021) · Nutrients · doi:10.3390/nu13010203 · Cited by 345 · see citing works
“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].”
BackgroundInfluentialVarani, J., Spearman, D., Perone, P., Fligiel, S., Datta, S. C., Wang, Z. Q., Shao, Y., Kang, S., Fisher, G. J., & Voorhees, J. J. (2001) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64040-0 · Cited by 333 · see citing works
Zasada, M., & Budzisz, E. (2019) · Advances in Dermatology and Allergology · doi:10.5114/ada.2019.87443 · Cited by 315 · see citing works
Hoang, H. T., Moon, J.-Y., & Lee, Y.-C. (2021) · Cosmetics · doi:10.3390/cosmetics8040106 · Cited by 329 · see citing works
Framework nucleic acids as programmable carrier for transdermal drug delivery
Wiraja, C., Zhu, Y. J., Lio, D. C. S., Yeo, D., Xie, M., Fang, W., Li, Q., Zheng, M., Steensel, M. A. M. V., Wang, L., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09029-9 · Cited by 296 · see citing works
Mechanisms and treatments of photoaging
Poon, F., Kang, S., & Chien, A. L. (2015) · Photodermatology, Photoimmunology & Photomedicine · doi:10.1111/phpp.12145 · Cited by 284 · see citing works
Fligiel, S., Varani, J., Datta, S. C., Kang, S., Fisher, G. J., & Voorhees, J. J. (2003) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.2003.12148.x · Cited by 283 · see citing works
Satheesh, N. K., & Fanta, S. W. (2019) · Food Science & Nutrition · doi:10.1002/fsn3.1063 · Cited by 272 · see citing works
Chung, J. H. (2003) · Photodermatology Photoimmunology & Photomedicine · doi:10.1034/j.1600-0781.2003.00027.x · Cited by 269 · see citing works
Impact of Retinoic Acid on Immune Cells and Inflammatory Diseases
Oliveira, L. D. M., Teixeira, F. M. E., & Sato, M. N. (2018) · Mediators of Inflammation · doi:10.1155/2018/3067126 · Cited by 267 · see citing works
Nusgens, B. V., Colige, A. C., Lambert, C. A., Lapière, C. M., Humbert, P., Rougier, A., Haftek, M., Richard, A., & Creidi, P. (2001) · Journal of Investigative Dermatology · doi:10.1046/j.0022-202x.2001.01362.x · Cited by 262 · see citing works
Mine, S., Fortunel, N. O., Pageon, H., & Asselineau, D. (2008) · PLoS ONE · doi:10.1371/journal.pone.0004066 · Cited by 255 · see citing works
Overview of skin aging and photoaging.
Helfrich, Y. R., Sachs, D. L., & Voorhees, J. J. (2008) · PubMed · Cited by 255 · see citing works
Proksch, E., Segger, D., Degwert, J., Schunck, M., Zague, V., & Oesser, S. (2013) · Skin Pharmacology and Physiology · doi:10.1159/000351376 · Cited by 251 · see citing works
Structural and Functional Changes and Possible Molecular Mechanisms in Aged Skin
Lee, H. J., Hong, Y., & Kim, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222212489 · Cited by 269 · see citing works
Improvement of Naturally Aged Skin With Vitamin A (Retinol)
Kafi, R., Kwak, H. S. R., Schumacher, W. E., Cho, S., Hanft, V. N., Hamilton, T. A., King, A. L., Neal, J. D., Varani, J., Fisher, G. J., et al. (2007) · Archives of Dermatology · doi:10.1001/archderm.143.5.606 · Cited by 241 · see citing works
Aging in the dermis: Fibroblast senescence and its significance
Zhang, J., Yu, H., Man, M., & Hu, L. (2023) · Aging Cell · doi:10.1111/acel.14054 · Cited by 249 · see citing works
Yaar, M., Eller, M. S., & Gilchrest, B. A. (2002) · Journal of Investigative Dermatology Symposium Proceedings · doi:10.1046/j.1523-1747.2002.19636.x · Cited by 233 · see citing works
Retinol-encapsulated low molecular water-soluble chitosan nanoparticles
Kim, D., JEONG, Y., CHOI, C., Roh, S., Kang, S. H., Jang, M., & Nah, J. (2006) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2006.03.040 · Cited by 227 · see citing works
The Pathobiology of Skin Aging
Russell-Goldman, E. E., & Murphy, G. F. (2020) · American Journal Of Pathology · doi:10.1016/j.ajpath.2020.03.007 · Cited by 219 · see citing works
In Situ Imaging of Tissue Remodeling with Collagen Hybridizing Peptides
Hwang, J., Huang, Y., Burwell, T. J., Peterson, N. C., Connor, J., Weiss, S. J., Yu, S. M., & Li, Y. (2017) · ACS Nano · doi:10.1021/acsnano.7b03150 · Cited by 208 · see citing works
Sanjeewa, K. K. A., Kim, E.-A. L., Son, K.-T., & Jeon, Y. (2016) · Journal of Photochemistry and Photobiology B Biology · doi:10.1016/j.jphotobiol.2016.06.027 · Cited by 206 · see citing works
Effects of Infrared Radiation and Heat on Human Skin Aging in vivo
Cho, S., Shin, M. H., Kim, Y. K., Seo, J., Lee, Y., Park, C., & Chung, J. H. (2009) · Journal of Investigative Dermatology Symposium Proceedings · doi:10.1038/jidsymp.2009.7 · Cited by 203 · see citing works
The Role of Vitamin A in Wound Healing
Polcz, M. E., & Barbul, A. (2019) · Nutrition in Clinical Practice · doi:10.1002/ncp.10376 · Cited by 205 · see citing works
Aslam, M. N., Lansky, E. S., & Varani, J. (2005) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2005.07.027 · Cited by 197 · see citing works
Varani, J., Schuger, L. A., Dame, M. K., Leonard, C., Fligiel, S., Kang, S., Fisher, G. J., & Voorhees, J. J. (2004) · Journal of Investigative Dermatology · doi:10.1111/j.0022-202x.2004.22614.x · Cited by 193 · see citing works
Han, A., Chien, A. L., & Kang, S. (2014) · Dermatologic Clinics · doi:10.1016/j.det.2014.03.015 · Cited by 194 · see citing works
Marcos‐Garcés, V., Aguilar, P. M., Serrano, C. B., García-Bustos, V., Seguí, J. B., Izquierdo, A. F., & Ruiz‐Saurí, A. (2014) · Journal of Anatomy · doi:10.1111/joa.12186 · Cited by 185 · see citing works
Anti-Aging Potential of Phytoextract Loaded-Pharmaceutical Creams for Human Skin Cell Longetivity
Jadoon, S., Karim, S., Asad, M. H. H. B., Akram, M. R., Khan, A. K., Malik, A., Chen, C.-Y., & Murtaza, G. (2015) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2015/709628 · Cited by 194 · see citing works
Rawlings, A. V. (2006) · International Journal of Cosmetic Science · doi:10.1111/j.1467-2494.2006.00318.x · Cited by 182 · see citing works
Review Article: A new wrinkle on old skin: the role of elastic fibres in skin ageing
Langton, A. K., Sherratt, M. J., Griffiths, C. E. M., & Watson, R. E. B. (2010) · International Journal of Cosmetic Science · doi:10.1111/j.1468-2494.2010.00574.x · Cited by 177 · see citing works
Sim, G.-S., Lee, B.-C., Cho, H. S., Lee, J. W., Kim, J., Lee, D. H., Kim, J.-H., Pyo, H.-B., Moon, D. C., Oh, K., et al. (2007) · Archives of Pharmacal Research · doi:10.1007/bf02977608 · Cited by 172 · see citing works
Applications for Marine Resources in Cosmetics
Guillerme, J.-B., Couteau, C., & Coiffard, L. J. M. (2017) · Cosmetics · doi:10.3390/cosmetics4030035 · Cited by 172 · see citing works
In vitro studies to evaluate the wound healing properties of Calendula officinalis extracts
Nicolaus, C., Junghanns, S., Hartmann, A., Murillo, R., Ganzera, M., & Merfort, I. (2016) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2016.12.006 · Cited by 171 · see citing works
Angiogenesis in skin aging and photoaging
CHUNG, J. H., & EUN, H. C. (2007) · The Journal of Dermatology · doi:10.1111/j.1346-8138.2007.00341.x · Cited by 169 · see citing works
Kim, D. J., Iwasaki, A., Chien, A. L.-L., & Kang, S. (2022) · JCI Insight · doi:10.1172/jci.insight.156344 · Cited by 166 · see citing works
Reichrath, J., Lehmann, B., Carlberg, C., Varani, J., & Zouboulis, C. C. (2007) · Hormone and Metabolic Research · doi:10.1055/s-2007-958715 · Cited by 164 · see citing works
Ultraviolet Modulation of Human Macrophage Metalloelastase in Human Skin In Vivo
Chung, J. H., Seo, J. Y., Lee, M. K., Eun, H. C., Lee, J. H., Kang, S., Fisher, G. J., & Voorhees, J. J. (2002) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.2002.01844.x · Cited by 163 · see citing works
Varani, J., Perone, P., Fligiel, S., Fisher, G. J., & Voorhees, J. J. (2002) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.2002.01810.x · Cited by 162 · see citing works
Kong, R., Cui, Y., Fisher, G. J., Wang, X., Chen, Y., Schneider, L. M., & Majmudar, G. (2015) · Journal of Cosmetic Dermatology · doi:10.1111/jocd.12193 · Cited by 163 · see citing works
Ahmad, J. (2015) · Diabetes & Metabolic Syndrome Clinical Research & Reviews · doi:10.1016/j.dsx.2015.04.002 · Cited by 156 · see citing works
Kwon, K.-R., Alam, M. B., Park, J., Kim, T., & Lee, S. (2019) · Nutrients · doi:10.3390/nu11061341 · Cited by 154 · see citing works
Barolet, D., Roberge, C. J., Auger, F. A., Boucher, A., & Germain, L. (2009) · Journal of Investigative Dermatology · doi:10.1038/jid.2009.186 · Cited by 146 · see citing works
Topical Retinoids in Acne Vulgaris
Thielitz, A., & Gollnick, H. P. M. (2008) · American Journal of Clinical Dermatology · doi:10.2165/0128071-200809060-00003 · Cited by 145 · see citing works
Chiu, A. E., & Kimball, A. B. (2003) · British Journal of Dermatology · doi:10.1046/j.1365-2133.2003.05540.x · Cited by 142 · see citing works
Papakonstantinou, E., Aletras, A. J., Glass, E., Tsogas, P., Dionyssopoulos, A., Adjaye, J., Fimmel, S., Gouvousis, P., Herwig, R., Lehrach, H. R., et al. (2005) · Journal of Investigative Dermatology · doi:10.1111/j.0022-202x.2005.23848.x · Cited by 140 · see citing works
An In Vivo Confocal Raman Study of the Delivery of Trans-Retinol to the Skin
Pudney, P. D. A., Mélot, M., Caspers, P. J., van der Pol, A., & Puppels, G. J. (2007) · Applied Spectroscopy · doi:10.1366/000370207781540042 · Cited by 139 · see citing works
Son, E. D., Lee, J., Lee, S., Kim, M. S., Lee, B. G., Chang, I. S., & Chung, J. H. (2005) · Journal of Investigative Dermatology · doi:10.1111/j.0022-202x.2005.23736.x · Cited by 136 · see citing works
Mélot, M., Pudney, P. D. A., Williamson, A., Caspers, P. J., van der Pol, A., & Puppels, G. J. (2009) · Journal of Controlled Release · doi:10.1016/j.jconrel.2009.04.023 · Cited by 133 · see citing works
Fucoidan inhibits UVB-induced MMP-1 expression in human skin fibroblasts
Moon, H. J., Lee, S. R., Shim, S. N., Jeong, S. H., Stonik, V. A., Rasskazov, V. A., Zvyagintseva, T., & Lee, Y. H. (2008) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.31.284 · Cited by 131 · see citing works
11β-Hydroxysteroid dehydrogenase blockade prevents age-induced skin structure and function defects
Tiganescu, A., Tahrani, A. A., Morgan, S., Otranto, M., Desmoulière, A., Abrahams, L., Hassan-Smith, Z. K., Walker, E. A., Rabbitt, E. H., Cooper, M. S., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci64162 · Cited by 132 · see citing works
Quan, T., He, T., Shao, Y., Lin, L., Kang, S., Voorhees, J. J., & Fisher, G. J. (2006) · American Journal Of Pathology · doi:10.2353/ajpath.2006.060128 · Cited by 130 · see citing works
Role of Matrix Metalloproteinases in Skin Ageing
Sárdy, M. (2009) · Connective Tissue Research · doi:10.1080/03008200802585622 · Cited by 134 · see citing works
The Potential of Topical and Injectable Growth Factors and Cytokines for Skin Rejuvenation
Fabi, S. G., & Sundaram, H. A. (2014) · Facial Plastic Surgery · doi:10.1055/s-0034-1372423 · Cited by 128 · see citing works
Liu, R., Bal, H. S., Desta, T., Behl, Y., & Graves, D. T. (2006) · American Journal Of Pathology · doi:10.2353/ajpath.2006.050907 · Cited by 126 · see citing works
Greul, A., Grundmann, J., Heinrich, F., Pfitzner, I., Bernhardt, J. H., Ambach, A., Biesalski, H. K., & Gollnick, H. P. M. (2002) · Skin Pharmacology and Physiology · doi:10.1159/000064534 · Cited by 124 · see citing works
Retinoids – Which Dermatological Indications Will Benefit in the Near Future?
Zouboulis, C. C. (2001) · Skin Pharmacology and Physiology · doi:10.1159/000056361 · Cited by 124 · see citing works
Photoprotective and anti-skin-aging effects of eicosapentaenoic acid in human skin in vivo
Kim, H. H., Cho, S., Lee, S., Kim, K. H., Cho, K. H., Eun, H. C., & Chung, J. H. (2006) · Journal of Lipid Research · doi:10.1194/jlr.m500420-jlr200 · Cited by 124 · see citing works
Eicosapentaenoic acid inhibits UV-induced MMP-1 expression in human dermal fibroblasts
Kim, H. H., Shin, C. M., Park, C., Kim, K. H., Cho, K. H., Eun, H. C., & Chung, J. H. (2005) · Journal of Lipid Research · doi:10.1194/jlr.m500105-jlr200 · Cited by 119 · see citing works
The role of estrogen deficiency in skin ageing and wound healing
Emmerson, E., & Hardman, M. J. (2012) · Biogerontology · doi:10.1007/s10522-011-9322-y · Cited by 118 · see citing works
Ryu, B., Qian, Z.-J., Kim, M.-M., Nam, K. W., & Kim, S.-K. (2009) · Radiation Physics and Chemistry · doi:10.1016/j.radphyschem.2008.09.001 · Cited by 113 · see citing works
Oxidative Stress and Human Skin Connective Tissue Aging
Tu, Y., & Quan, T. (2016) · Cosmetics · doi:10.3390/cosmetics3030028 · Cited by 114 · see citing works
Rittié, L., Varani, J., Kang, S., Voorhees, J. J., & Fisher, G. J. (2006) · Journal of Investigative Dermatology · doi:10.1038/sj.jid.5700202 · Cited by 114 · see citing works
Lee, Y., Kim, Y. K., Kim, K. H., Park, S. J., Kim, S. J., & Chung, J. H. (2009) · Journal of Cellular Physiology · doi:10.1002/jcp.21729 · Cited by 107 · see citing works
Scarless wound healing: From development to senescence
Pratsinis, H., Mavrogonatou, E., & Kletsas, D. (2019) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2018.04.011 · Cited by 103 · see citing works
Fujii, T., Wakaizumi, M., Ikami, T., & Saito, M. (2008) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2008.05.039 · Cited by 109 · see citing works
Reversing wrinkled skin and hair loss in mice by restoring mitochondrial function
Singh, B., Schoeb, T. R., Bajpai, P., Slominski, A. T., & Singh, K. K. (2018) · Cell Death and Disease · doi:10.1038/s41419-018-0765-9 · Cited by 107 · see citing works
Chung, J. H., Hanft, V. N., & Kang, S. (2003) · Journal of the American Academy of Dermatology · doi:10.1067/s0190-9622(03)02127-3 · Cited by 105 · see citing works
Li, W. H., Lee, Y. M., Kim, J. Y., Kang, S., Kim, S., Kim, K. H., Park, C., & Chung, J. H. (2007) · Journal of Investigative Dermatology · doi:10.1038/sj.jid.5700880 · Cited by 103 · see citing works
H2O2 Accumulation by Catalase Reduction Changes MAP Kinase Signaling in Aged Human Skin In Vivo
Shin, M. H., Rhie, G., Kim, Y. K., Park, C., Cho, K. H., Kim, K. H., Eun, H. C., & Chung, J. H. (2005) · Journal of Investigative Dermatology · doi:10.1111/j.0022-202x.2005.23823.x · Cited by 103 · see citing works
Sachs, D. L., Varani, J., Chubb, H., Fligiel, S. E. G., Cui, Y., Calderone, K., Helfrich, Y., Fisher, G. J., & Voorhees, J. J. (2019) · Journal of the American Academy of Dermatology · doi:10.1016/j.jaad.2019.03.081 · Cited by 102 · see citing works
Fisher, G. J., Wang, B., Cui, Y., Shi, M., Zhao, Y., Quan, T., & Voorhees, J. J. (2023) · Journal of Cell Communication and Signaling · doi:10.1007/s12079-023-00743-0 · Cited by 103 · see citing works
Nutrition and cutaneous wound healing
Grada, A. A., & Phillips, T. J. (2021) · Clinics in Dermatology · doi:10.1016/j.clindermatol.2021.10.002 · Cited by 108 · see citing works
Farrukh, M. R., Nissar, U.-A., Afnan, Q., Rafiq, R. A., Sharma, L., Amin, S., Kaiser, P. J., Sharma, P. R., & Tasduq, S. A. (2014) · Journal of Dermatological Science · doi:10.1016/j.jdermsci.2014.03.005 · Cited by 100 · see citing works
Koehler, M. J., Hahn, S., Preller, A., Elsner, P. U., Ziemer, M., Bauer, A., König, K., Bückle, R., Fluhr, J. W., & Kaatz, M. (2008) · Experimental Dermatology · doi:10.1111/j.1600-0625.2007.00669.x · Cited by 98 · see citing works
Skin ageing and topical rejuvenation strategies
Griffiths, T. W., Watson, R. E. B., & Langton, A. K. (2023) · British Journal of Dermatology · doi:10.1093/bjd/ljad282 · Cited by 108 · see citing works
The role of collagen and elastin in aged skin: an image processing approach
Tzaphlidou, M. (2003) · Micron · doi:10.1016/j.micron.2003.11.003 · Cited by 103 · see citing works
Effect of aging on cellular mechanotransduction
Wu, M., Fannin, J. C., Rice, K. M., Wang, B., & Blough, E. R. (2009) · Ageing Research Reviews · doi:10.1016/j.arr.2009.11.002 · Cited by 95 · see citing works
Darlenski, R., Surber, C., & Fluhr, J. W. (2010) · British Journal of Dermatology · doi:10.1111/j.1365-2133.2010.09936.x · Cited by 100 · see citing works
Biochemical, structural and physical changes in aging human skin, and their relationship
Park, S. (2022) · Biogerontology · doi:10.1007/s10522-022-09959-w · Cited by 100 · see citing works
Nutrition in wound healing: investigation of the molecular mechanisms, a narrative review
Palmieri, B., Vadalà, M., & Laurino, C. (2019) · Journal of Wound Care · doi:10.12968/jowc.2019.28.10.683 · Cited by 93 · see citing works
Skin Immune Systems and Inflammation: Protector of the Skin or Promoter of Aging?
Bennett, M. F., Robinson, M. K., Baron, E. D., & Cooper, K. D. (2008) · Journal of Investigative Dermatology Symposium Proceedings · doi:10.1038/jidsymp.2008.3 · Cited by 92 · see citing works
Philips, N. E., Conte, J., Chen, Y., Natrajan, P., Taw, M. N., Keller, T., Givant, J., Tuason, M., Dulaj, L., Leonardi, D., et al. (2009) · Archives of Dermatological Research · doi:10.1007/s00403-009-0950-x · Cited by 91 · see citing works
Hwang, E., Lee, D.-G., Park, S. H., Oh, M. S., & Kim, S. Y. (2014) · Journal of Medicinal Food · doi:10.1089/jmf.2013.2999 · Cited by 90 · see citing works
Endogenous growth factors as cosmeceuticals
Mehta, R., & FITZPATRICK, R. E. (2007) · Dermatologic Therapy · doi:10.1111/j.1529-8019.2007.00149.x · Cited by 90 · see citing works
Roeck, K., Grandoch, M., Majora, M., Krutmann, J., & Fischer, J. W. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.201665 · Cited by 90 · see citing works
- 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 ›
Are you an author, or do you see a problem with this page? Request a review
