Molecular basis of retinol anti‐ageing properties in naturally aged human skin in vivo
Open accessAbstract
OBJECTIVE: Retinoic acid has been shown to improve the aged-appearing skin. However, less is known about the anti-ageing effects of retinol (ROL, vitamin A), a precursor of retinoic acid, in aged human skin in vivo. This study aimed to investigate the molecular basis of ROL anti-ageing properties in naturally aged human skin in vivo. METHODS: Sun-protected buttock skin (76 ± 6 years old, n = 12) was topically treated with 0.4% ROL and its vehicle for 7 days. The effects of topical ROL on skin epidermis and dermis were evaluated by immunohistochemistry, in situ hybridization, Northern analysis, real-time RT-PCR and Western analysis. Collagen fibrils nanoscale structure and surface topology were analysed by atomic force microscopy. RESULTS: Topical ROL shows remarkable anti-ageing effects through three major types of skin cells: epidermal keratinocytes, dermal endothelial cells and fibroblasts. Topical ROL significantly increased epidermal thickness by stimulating keratinocytes proliferation and upregulation of c-Jun transcription factor. In addition to epidermal changes, topical ROL significantly improved dermal extracellular matrix (ECM) microenvironment; increasing dermal vascularity by stimulating endothelial cells proliferation and ECM production (type I collagen, fibronectin and elastin) by activating dermal fibroblasts. Topical ROL also stimulates TGF-β/CTGF pathway, the major regulator of ECM homeostasis, and thus enriched the deposition of ECM in aged human skin in vivo. 0.4% topical ROL achieved similar results as seen with topical retinoic acid, the biologically active form of ROL, without causing noticeable signs of retinoid side effects. CONCLUSION: 0.4% topical ROL shows remarkable anti-ageing effects through improvement of the homeostasis of epidermis and dermis by stimulating the proliferation of keratinocytes and endothelial cells, and activating dermal fibroblasts. These data provide evidence that 0.4% topical ROL is a promising and safe treatment to improve the naturally aged human 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?
Topical retinol improves the dermal extracellular matrix microenvironment (type I collagen, fibronectin, and elastin) and activates ECM-producing cells in aged skin.
“Topical retinol improves the dermal extracellular matrix (ECM) microenvironment (type I collagen, fibronectin, and elastin) and activates ECM-producing cells in aged skin [32,38].”
From Bioactive Compounds for Skin Health: A Review (2021) · cites this paper as [38]
The anti-ageing effects of retinoids are mediated by epidermal keratinocytes, dermal endothelial cells and fibroblasts.
“The anti-ageing effects of retinoids are mediated by three major types of skin cells: epidermal keratinocytes, dermal endothelial cells and fibroblasts [38].”
From Bioactive Compounds for Skin Health: A Review (2021) · cites this paper as [38]
Activation of fibroblast production is stimulated through the TGF-β/CTGF pathway, the major regulator of ECM homeostasis.
“The activation of fibroblast production is stimulated through the TGF-β/CTGF pathway, the major regulator of ECM homeostasis [38].”
From Bioactive Compounds for Skin Health: A Review (2021) · cites this paper as [38]
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
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-citationBissell, M. J., & Hines, W. C. (2011) · Nature Medicine · doi:10.1038/nm.2328 · Cited by 1,516 · see citing works
Daynes, R. A., Araneo, B. A., Ershler, W. B., Maloney, C., Li, G. Z., & Ryu, S. Y. (1993) · The Journal of Immunology · doi:10.4049/jimmunol.150.12.5219 · Cited by 1,264 · 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
Quan, T., & Fisher, G. J. (2015) · Gerontology · doi:10.1159/000371708 · Cited by 464 · see citing works
Self-citationJacob, M. P. (2003) · Biomedicine & Pharmacotherapy · doi:10.1016/s0753-3322(03)00065-9 · Cited by 371 · see citing works
Clinical aspects and molecular diagnostics of skin aging
Zouboulis, C. C., & Makrantonaki, E. (2011) · Clinics in Dermatology · doi:10.1016/j.clindermatol.2010.07.001 · Cited by 341 · see citing works
Bissell, M. J., Kenny, P. A., & Radisky, D. C. (2005) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2005.70.013 · Cited by 297 · 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
Quan, T., Wang, F., Shao, Y., Rittié, L., Xia, W., Orringer, J. S., Voorhees, J. J., & Fisher, G. J. (2012) · Journal of Investigative Dermatology · doi:10.1038/jid.2012.364 · Cited by 248 · see citing works
Self-citationQuan, T., Shao, Y., He, T., Voorhees, J. J., & Fisher, G. J. (2010) · Journal of Investigative Dermatology · doi:10.1038/jid.2009.224 · Cited by 239 · see citing works
Self-citationYaar, 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 · cited 1× · see citing works
“Histological and ultrastructural studies have revealed skin undergoes remarkable morphologic changes with ageing, which are primarily characterized by thinner epidermis and dermis with reduced numbers of epidermal keratinocytes and dermal stromal cells, respectively [7, 8].”
BackgroundTransport and Metabolism of Vitamin A
Blomhoff, R. (2009) · Nutrition Reviews · doi:10.1111/j.1753-4887.1994.tb01382.x · Cited by 175 · see citing works
Fisher, G. J., Talwar, H. S., Xiao, J. H., Datta, S. C., Reddy, A. P., Gaub, M. P., Rochette‐Egly, C., Chambon, P., & Voorhees, J. J. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)32039-2 · Cited by 169 · see citing works
Self-citationAngiogenesis 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
Ultraviolet Irradiation Alters Transforming Growth Factor β/Smad Pathway in Human Skin In Vivo
Quan, T., He, T., Kang, S., Voorhees, J. J., & Fisher, G. J. (2002) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.2002.01834.x · Cited by 169 · see citing works
Self-citationExtracellular Matrix: A Matter of Life and Death
Marastoni, S., Ligresti, G., Lorenzon, E., Colombatti, A., & Mongiat, M. (2008) · Connective Tissue Research · doi:10.1080/03008200802143190 · Cited by 166 · 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
Self-citationFisher, G. J., Shao, Y., He, T., Qin, Z., Perry, D., Voorhees, J. J., & Quan, T. (2015) · Aging Cell · doi:10.1111/acel.12410 · Cited by 125 · see citing works
Self-citationDifferential Regulation of Retinoic Acid Receptors and Binding Proteins in Human Skin
Elder, J. T., Åström, A., Pettersson, U., Tavakkol, A., Griffiths, C. E. M., Krust, A., Kastner, P., Chambon, P., & Voorhees, J. J. (1992) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12499896 · Cited by 116 · see citing works
Self-citationMolecular Mechanisms of Cutaneous Aging: Connective Tissue Alterations in the Dermis
Uitto, J., & Bernstein, E. F. (1998) · Journal of Investigative Dermatology Symposium Proceedings · doi:10.1038/jidsymp.1998.10 · Cited by 108 · see citing works
Fisher, G. J., Talwar, H. S., Lin, J., & Voorhees, J. J. (1999) · Photochemistry and Photobiology · doi:10.1111/j.1751-1097.1999.tb03268.x · Cited by 107 · see citing works
Self-citationDarlenski, 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
Quan, C., Cho, M. K., Shao, Y., Mianecki-Morton, L., Liao, E. A., Perry, D., & Quan, T. (2015) · Protein & Cell · doi:10.1007/s13238-015-0198-5 · Cited by 83 · see citing works
Self-citationQuan, C., Cho, M. K., Perry, D., & Quan, T. (2015) · Journal of Biomedical Science · doi:10.1186/s12929-015-0167-6 · Cited by 82 · see citing works
Self-citationMolecular Mechanisms of Cutaneous Aging: Connective Tissue Alterations in the Dermis
Uitto, J., & Bernstein, E. F. (1998) · Journal of Investigative Dermatology · doi:10.1038/jidsp.1998.10 · Cited by 81 · see citing works
Quan, T., He, T., Kang, S., Voorhees, J. J., & Fisher, G. J. (2002) · Journal of Investigative Dermatology · doi:10.1046/j.0022-202x.2001.01678.x · Cited by 80 · see citing works
Self-citationQuan, T., Qin, Z., Shao, Y., Xu, Y., Voorhees, J. J., & Fisher, G. J. (2011) · Experimental Dermatology · doi:10.1111/j.1600-0625.2011.01278.x · Cited by 45 · see citing works
Self-citationThomas, D. R., & Burkemper, N. M. (2013) · Clinics in Geriatric Medicine · doi:10.1016/j.cger.2013.02.001 · Cited by 28 · see citing works
Di, W. J., Li, X.-Y., Åström, A., et al. (1998) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.1998.00455.x · Cited by 13 · see citing works
Worley, C. A. (2006) · PubMed · Cited by 13 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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
“The activation of fibroblast production is stimulated through the TGF-β/CTGF pathway, the major regulator of ECM homeostasis [38].”
BackgroundInfluentialZasada, M., & Budzisz, E. (2019) · Advances in Dermatology and Allergology · doi:10.5114/ada.2019.87443 · Cited by 315 · see citing works
- Authors
- Shao, Y., He, T., Fisher, G. J., Voorhees, J. J., & Quan, T.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Quan, T.
- Venue
- International Journal of Cosmetic Science
- Publisher
- Wiley
- Published
- 2016-07-04
- Volume
- 39
- Issue
- 1
- Pages
- 56-65
- ISSN
- 0142-5463 (ISSN-L)
- 1468-2494
- PMC
- PMC5136519
- OpenAlex
- W2409978204
- Cited by
- 130
- References
- 32
- Citations by year
- 2026: 13 · 2025: 21 · 2024: 18 · 2023: 21 · 2022: 12 · 2021: 10 · 2020: 9 · 2019: 17 · 2018: 5 · 2017: 3 · 2016: 1
- FWCI
- 10.36
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- International Journal of Cosmetic Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Deep Blue (University of Michigan) (submittedVersion)
- Funders
- National Institutes of Health (AG019364, ES014697)
- Dermatology Foundation
- Topics
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Health Sciences › Medicine › Dermatology › Facial Rejuvenation and Surgery Techniques
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- retinol, vitamin A, anti-aging, skin aging, retinoic acid, keratinocyte proliferation, c-Jun, dermal fibroblasts, endothelial cells, extracellular matrix, type I collagen, fibronectin, elastin, epidermal thickness, collagen fibril structure
- MeSH terms
- Aging, Collagen, Humans, Skin, Vitamin A, Transforming Growth Factor beta, Microscopy, Atomic Force, Connective Tissue Growth Factor
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
