Improvement of Naturally Aged Skin With Vitamin A (Retinol) | Dermatology | JAMA Dermatology | JAMA Network
[Skip to Navigation]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address Please contact the publisher to request reinstatement.
Fisher  GJDatta  STalwar  HS  et al.  Molecular basis of sun-induced premature skin aging and retinoid antagonism.  Nature 1996;379335- 339PubMedGoogle ScholarCrossref
Fisher  GJWang  ZQDatta  SCVarani  JKang  SVoorhees  JJ Pathophysiology of premature skin aging induced by ultraviolet light.  N Engl J Med 1997;3371419- 1428PubMedGoogle ScholarCrossref
Weiss  JSEllis  CNHeadington  JT  et al.  Topical tretinoin for photoaged skin: a double-blind vehicle-controlled study.  JAMA 1988;259527- 532PubMedGoogle ScholarCrossref
Kang  SLeyden  JJLowe  NJ  et al.  Tazarotene cream for the treatment of facial photodamage: a multicenter, investigator-masked, randomized, vehicle-controlled, parallel comparison of tazarotene 0.01%, 0.025%, 0.05%, and 0.1% creams and tretinoin 0.05% emollient cream applied once-daily for 24 weeks.  Arch Dermatol 2001;1371597- 1604PubMedGoogle ScholarCrossref
Fisher  GJKang  SVarani  J  et al.  Mechanisms of photoaging and chronological skin aging.  Arch Dermatol 2002;1381462- 1470PubMedGoogle ScholarCrossref
Gilchrest  BA A review of skin ageing and its medical therapy.  Br J Dermatol 1996;135867- 875PubMedGoogle ScholarCrossref
Varani  JWarner  RLGharaee-Kermani  M  et al.  Vitamin A antagonizes decreased cell growth and elevated collagen-degrading matrix metalloproteinases and stimulates collagen accumulation in naturally aged human skin.  J Invest Dermatol 2000;114480- 486PubMedGoogle ScholarCrossref
West  MD The cellular and molecular biology of skin aging.  Arch Dermatol 1994;13087- 95PubMedGoogle ScholarCrossref
Pieraggi  MTJulian  MBouissou  H Fibroblast changes in cutaneous aging.  Virchows Arch A Pathol Anat Histopathol 1984;402275- 287PubMedGoogle ScholarCrossref
Griffiths  CEMRussman  ANMajmudar  GSinger  RSHamilton  TAVoorhees  JJ Restoration of collagen formation in photodamaged human skin by tretinoin (retinoic acid).  N Engl J Med 1993;329530- 535PubMedGoogle ScholarCrossref
Orringer  JSKang  SJohnson  TM  et al.  Connective tissue remodeling induced by CO2 laser resurfacing of photodamaged human skin.  Arch Dermatol 2004;1401326- 1332PubMedGoogle Scholar
Griffiths  CEMKang  SEllis  CN  et al.  Two concentrations of topical tretinoin (retinoic acid) cause similar improvement of photoaging but different degrees of irritation: a double-blind, vehicle-controlled comparison of tretinoin 0.1% and 0.025% creams.  Arch Dermatol 1995;1311037- 1044PubMedGoogle ScholarCrossref
Weinstein  GDNigra  TPPochi  PE  et al.  Topical tretinoin for treatment of photodamaged skin: a multicenter study.  Arch Dermatol 1991;127659- 665PubMedGoogle ScholarCrossref
Cho  SLowe  LHamilton  TAFisher  GJVoorhees  JJKang  S Long-term treatment of photoaged human skin with topical retinoic acid improves epidermal cell atypia and thickens collagen band in the papillary dermis.  J Am Acad Dermatol 2005;53769- 774PubMedGoogle ScholarCrossref
Kang  SKrueger  GTanghetti  E  et al.  A multicenter, randomized, double-blind trial of tazarotene 0.1% cream in the treatment of photodamage.  J Am Acad Dermatol 2005;52268- 274PubMedGoogle ScholarCrossref
Kang  SDuell  EAFisher  GJ  et al.  Application of retinol to human skin in vivo induces epidermal hyperplasia and cellular retinoid binding proteins characteristic of retinoic acid but without measurable retinoic acid levels or irritation.  J Invest Dermatol 1995;105549- 556PubMedGoogle ScholarCrossref
Kang  SDuell  EAKim  KJVoorhees  JJ Liarozole inhibits human epidermal retinoic acid 4-hydroxylase activity and differentially augments human skin responses to retinoic acid and retinol in vivo.  J Invest Dermatol 1996;107183- 187PubMedGoogle ScholarCrossref
Astrom  APettersson  UChambon  PVoorhees  JJ Retinoic acid induction of human cellular retinoic acid-binding protein-II gene transcription is mediated by retinoic acid receptor-retinoid X receptor heterodimers bound to one far upstream retinoic acid-responsive element with 5-base pair spacing.  J Biol Chem 1994;26922334- 22339PubMedGoogle Scholar
Elder  JTKaplan  ACromie  MAKang  SVoorhees  JJ Retinoid induction of CRABP-II mRNA in human dermal fibroblasts: use as a retinoid bioassay.  J Invest Dermatol 1996;106517- 521PubMedGoogle ScholarCrossref
Fisher  GJDatta  SWang  ZQ  et al.  c-Jun-dependent inhibition of cutaneous procollagen transcription following ultraviolet irradiation is reversed by all-trans retinoic acid.  J Clin Invest 2000;106663- 670PubMedGoogle ScholarCrossref
Quan  THe  TKang  SVoorhees  JFisher  G Solar ultraviolet irradiation reduces collagen in photoaged human skin by blocking transforming growth factor-β type II receptor/Smad signaling.  Am J Pathol 2004;165741- 751PubMedGoogle ScholarCrossref
Quan  THe  TShao  Y  et al.  Elevated cysteine-rich 61 mediates aberrant collagen homeostasis in chronologically aged and photoaged human skin.  Am J Pathol 2006;169482- 490PubMedGoogle ScholarCrossref
Smith  ESFleischer  AB  JrFeldman  SR Demographics of aging and skin disease.  Clin Geriatr Med 2001;17631- 641PubMedGoogle ScholarCrossref
Yu  LRosi  YOfori  AKing  AVoorhees  JJKang  S Intrinsic skin aging: validation of a photonumeric scale and risk factors that accelerate the process [abstract].  J Invest Dermatol 2005;124A54Google Scholar
Kang  SFisher  GJVoorhees  JJ Photoaging and topical tretinoin: therapy, pathogenesis, and prevention.  Arch Dermatol 1997;1331280- 1284PubMedGoogle ScholarCrossref
Kang  SVoorhees  JJ Photoaging therapy with topical tretinoin: an evidence-based analysis.  J Am Acad Dermatol 1998;39S55- S61PubMedGoogle ScholarCrossref
Fisher  GJTavakkol  AGriffiths  CEM  et al.  Differential modulation of transforming growth facter-β1 expression and mucin deposition by retinoic acid and sodium lauryl sulfate in human skin.  J Invest Dermatol 1992;98102- 108PubMedGoogle ScholarCrossref
Silbert  JE Proteoglycans and glycosaminoglycans. Goldsmith  LAed. Biochemistry and Physiology of the Skin. New York, NY Oxford University1983;448- 461Google Scholar
Olsen  EAKatz  HILevine  N  et al.  Sustained improvement in photodamaged skin with reduced tretinoin emollient cream treatment regimen: effect of once-weekly and three-times-weekly applications.  J Am Acad Dermatol 1997;37227- 230PubMedGoogle ScholarCrossref
May 2007

Improvement of Naturally Aged Skin With Vitamin A (Retinol)

Author Affiliations

Author Affiliations: Department of Dermatology, University of Michigan Medical School, Ann Arbor. Drs Kafi and Kwak are now with the Department of Dermatology, Stanford Medical School, Palo Alto, Calif, and Dr Cho is now with the Department of Dermatology, Seoul National University, Seoul, South Korea.

Arch Dermatol. 2007;143(5):606-612. doi:10.1001/archderm.143.5.606

Objective  To evaluate the effectiveness of topical retinol (vitamin A) in improving the clinical signs of naturally aged skin.

Design  Randomized, double-blind, vehicle-controlled, left and right arm comparison study.

Setting  Academic referral center.

Patients  The study population comprised 36 elderly subjects (mean age, 87 years), residing in 2 senior citizen facilities.

Intervention  Topical 0.4% retinol lotion or its vehicle was applied at each visit by study personnel to either the right or the left arm, up to 3 times a week for 24 weeks.

Main Outcome Measures  Clinical assessment using a semiquantitative scale (0, none; 9, most severe) and biochemical measurements from skin biopsy specimens obtained from treated areas.

Results  After 24 weeks, an intent-to-treat analysis using the last-observation-carried-forward method revealed that there were significant differences between retinol-treated and vehicle-treated skin for changes in fine wrinkling scores (−1.64 [95% CI, −2.06 to −1.22] vs −0.08 [95% CI, −0.17 to 0.01]; P<.001). As measured in a subgroup, retinol treatment significantly increased glycosaminoglycan expression (P = .02 [n = 6]) and procollagen I immunostaining (P = .049 [n = 4]) compared with vehicle.

Conclusions  Topical retinol improves fine wrinkles associated with natural aging. Significant induction of glycosaminoglycan, which is known to retain substantial water, and increased collagen production are most likely responsible for wrinkle effacement. With greater skin matrix synthesis, retinol-treated aged skin is more likely to withstand skin injury and ulcer formation along with improved appearance.

Trial Registration Identifier: NCT00272610