Topical anti-aging agents: state-of-the-art review

Flora Ramona Sigit Prakoeswa(1*), Faradiba Maharani(2), Yohanes Aditya Adhi Satria(3), Ghina Shabrina Awanis(4), Astrida Fesky Febrianty(5)

(1) Faculty of Medicine, Universitas Muhammadiyah Surakarta/Department of Dermatology and Venerology, PKU Muhammadiyah Surakarta Hospital, Surakarta, Central Java, Indonesia
(2) Faculty of Medicine, Universitas Sebelas Maret, Surakarta, Central Java, Indonesia
(3) Faculty of Medicine, Universitas Sebelas Maret, Surakarta, Central Java, Indonesia
(4) Faculty of Medicine, Universitas Sebelas Maret, Surakarta, Central Java, Indonesia
(5) Faculty of Medicine, Universitas Sebelas Maret, Surakarta, Central Java, Indonesia
(*) Corresponding Author


Skin aging can be divided into intrinsic and extrinsic aging. Even though it is inevitable, symptoms of skin aging are a common concern for patients. As a result, there is a surge in the making of anti-aging cosmeceuticals. However, there is a lack of evidence-based data to support the usage of topical preparations as anti-aging treatments. Therefore, further studies are needed to explore topical treatment options for skin aging. This literature review discusses the mechanism of commonly used topical anti-aging agents and their adverse reactions.


antiaging; topical; adverse reactions

Full Text:



1. Shin JW, Kwon SH, Choi JY, Na JI, Huh CH, Choi HR, et al. Molecular mechanisms of dermal aging and antiaging approaches. Int J Mol Sci 2019; 20(9):2126.
2. Cho BA, Yoo SK, Seo JS. Signatures of photo-aging and intrinsic aging in skin were revealed by transcriptome network analysis. Aging 2018; 10(7):1609-26.
3. Zhang S, Duan E. Fighting against skin aging: the way from bench to bedside. Cell Transplant 2018; 27(5):729-38.
4. Gupta MA, Gilchrest BA. Psychosocial aspects of aging skin. Dermatol Clin 2005; 23(4):643-8.
5. Rattanawiwatpong P, Wanitphakdeedecha R, Bumrungpert A, Maiprasert M. Anti‐aging and brightening effects of a topical treatment containing vitamin C, vitamin E, and raspberry leaf cell culture extract: A split‐face, randomized controlled trial. J Cosmet Dermatol 2020; 19(3):671-6.
6. Draelos ZD. Cosmeceuticals: what’s real, what’s not. Dermatol Clin 2019; 37(1):107-15.
7. Chaudhary M, Khan A, Gupta M. Skin ageing: pathophysiology and current market treatment approaches. Curr Aging Sci 2020; 13(1):22-30.
8. Zasada M, Budzisz E. Retinoids: active molecules influencing skin structure formation in cosmetic and dermatological treatments. Postepy Dermatol Alergol 2019; 36(4):392-7.
9. Milosheska D, Roškar R. Use of retinoids in topical antiaging treatments: a focused review of clinical evidence for conventional and nanoformulations. Adv Ther 2022; 39(2):5351-75.
10. Buchanan P, Gilman R. Retinoids: literature review and suggested algorithm for use prior to facial resurfacing procedures. J Cutan Aesthetic Surg 2016; 9(3):139-44.
11. Yin S, Luo J, Qian A, Du J, Yang Q, Zhou S, et al. Retinoids activate the irritant receptor TRPV1 and produce sensory hypersensitivity. J Clin Invest 2013; 123(9):3941-51.
12. Safavynia SA, Goldstein PA. The role of neuroinflammation in postoperative cognitive dysfunction: moving from hypothesis to treatment. Front Psychiatry 2018; 9:752.
13. Imhof L, Leuthard D. Topical over-the-counter antiaging agents: an update and systematic review. Dermatology 2021; 237(2):217-29.
14. Mukherjee S, Date A, Patravale V, Korting HC, Roeder A, Weindl G. Retinoids in the treatment of skin aging: an overview of clinical efficacy and safety. Clin Interv Aging 2006; 1(4):327-48.
15. Irby CE, Yentzer BA, Feldman SR. A review of adapalene in the treatment of acne vulgaris. J Adolesc Health 2008; 43(2):421-4.
16. Rendon MI, Barkovic S. Clinical evaluation of a 4% hydroquinone + 1% retinol treatment regimen for improving melasma and photodamage in Fitzpatrick skin types III-VI. J Drugs Dermatol 2016; 15(11):1435-41.
17. Motamedi M, Chehade A, Sanghera R, Grewal P. A clinician’s guide to topical retinoids. J Cutan Med Surg 2022; 26(1):71-8.
18. Papakonstantinou E, Roth M, Karakiulakis G. Hyaluronic acid: a key molecule in skin aging. Dermatoendocrinol 2012; 4(3):253-8.
19. Draelos ZD, Diaz I, Namkoong J, Wu J, Boyd T. Efficacy evaluation of a topical hyaluronic acid serum in facial photoaging. Dermatol Ther 2021; 11(4):1385-94.
20. Madani ND, Malloy PJ, Rodriguez-Pombo P, Krishnan AV, Feldman D. Candida albicans estrogen-binding protein gene encodes an oxidoreductase that is inhibited by estradiol. Proc Natl Acad Sci U S A 1994; 91(3):922-6.
21. Pavicic T, Gauglitz GG, Lersch P, Schwach-Abdellaoui K, Malle B, Korting HC, et al. Efficacy of cream-based novel formulations of hyaluronic acid of different molecular weights in anti-wrinkle treatment. J Drugs Dermatol 2011; 10(9):990-1000.
22. Poetschke J, Schwaiger H, Steckmeier S, Ruzicka T, Gauglitz GG. Anti-wrinkle creams with hyaluronic acid: How effective are they? MMW-Fortschritte Med 2016; 158 Suppl 4:1-6.
23. Juncan AM, Moisă DG, Santini A, Morgovan C, Rus LL, Vonica-Țincu AL, et al. Advantages of hyaluronic acid and its combination with other bioactive ingredients in cosmeceuticals. Molecules 2021; 26(15):4429.
24. Al-Niaimi F, Chiang NYZ. Topical vitamin c and the skin: mechanisms of action and clinical applications. J Clin Aesthetic Dermatol 2017; 10(7):14-7.
25. Caritá AC, Fonseca-Santos B, Shultz JD, Michniak-Kohn B, Chorilli M, Leonardi GR. Vitamin C: One compound, several uses. Advances for delivery, efficiency and stability. Nanomedicine 2020; 24:102117.
26. Drouin G, Godin JR, Pagé B. The genetics of vitamin c loss in vertebrates. Curr Genomics 2011; 12(5):371-8.
27. Lykkesfeldt J, Tveden-Nyborg P. The pharmacokinetics of vitamin C. Nutrients 2019; 11(10):2412.
28. Chambial S, Dwivedi S, Shukla KK, John PJ, Sharma P. Vitamin C in Disease Prevention and Cure: An Overview. Indian J Clin Biochem 2013; 28(4):314-28.
29. Telang PS. Vitamin C in dermatology. Indian Dermatol Online J 2013; 4(2):143-6.
30. Levine M, Padayatty SJ, Espey MG. Vitamin C: a concentration-function approach yields pharmacology and therapeutic discoveries. Adv Nutr 2011; 2(2):78–88.
31. Vissers MCM, Das AB. Potential mechanisms of action for vitamin C in cancer: reviewing the evidence. Front Physiol 2018; 9:809.
32. Pullar JM, Carr AC, Vissers MCM. The roles of vitamin C in skin health. Nutrients 2017; 9(8):866.
33. Padayatty SJ, Levine M. Vitamin C physiology: the known and the unknown and Goldilocks. Oral Dis 2016; 22(6):463-93.
34. Chen L, Hu JY, Wang SQ. The role of antioxidants in photoprotection: a critical review. J Am Acad Dermatol 2012; 67(5):1013-24.
35. Sunil Kumar BV, Singh S, Verma R. Anticancer potential of dietary vitamin D and ascorbic acid: A review. Crit Rev Food Sci Nutr 2017; 57(12):2623-35.
36. Sanadi RM, Deshmukh RS. The effect of Vitamin C on melanin pigmentation – A systematic review. J Oral Maxillofac Pathol 2020; 24(2):374-82.
37. De Dormael R, Bastien P, Sextius P, Gueniche A, Ye D, Tran C, et al. Vitamin c prevents ultraviolet-induced pigmentation in healthy volunteers: bayesian meta-analysis results from 31 randomized controlled versus vehicle clinical studies. J Clin Aesthet Dermatol 2019; 12(2):E53-9.
38. Jiang Q. Natural forms of vitamin E: metabolism, antioxidant and anti-inflammatory activities and the role in disease prevention and therapy. Free Radic Biol Me. 2014; 72:76-90.
39. Rizvi S, Raza ST, Ahmed F, Ahmad A, Abbas S, Mahdi F. The role of vitamin e in human health and some diseases. Sultan Qaboos Univ Med J 2014; 14(2):e157-65.
40. Traber MG, Manor D. Vitamin E. Adv Nutr 2012; 3(3):330-1.
41. Flory S, Birringer M, Frank J. Bioavailability and metabolism of vitamin E. In: Weber P, Birringer M, Blumberg JB, Eggersdorfer M, Frank J, editors. Vitamin E in human health [Internet]. Cham: Springer International Publishing; 2019 [cited 2022 Jul 20]. p. 31–41. (Nutrition and Health).
42. Mohd Zaffarin AS, Ng SF, Ng MH, Hassan H, Alias E. Pharmacology and pharmacokinetics of vitamin E: nanoformulations to enhance bioavailability. Int J Nanomedicine 2020; 15:9961-74. 10.2147/IJN.S276355
43. Baxter LL, Marugan JJ, Xiao J, Incao A, McKew JC, Zheng W, et al. Plasma and tissue concentrations of α-tocopherol and δ-tocopherol following high dose dietary supplementation in mice. Nutrients 2012; 4(6):467-90.
44. Kiyose C. Absorption, transportation, and distribution of vitamin E homologs. Free Radic Biol Med 2021; 177:226-37.
45. Keen MA, Hassan I. Vitamin E in dermatology. Indian Dermatol Online J 2016; 7(4):311-5.
46. Thiele JJ, Hsieh SN, Ekanayake-Mudiyanselage S. Vitamin E: critical review of its current use in cosmetic and clinical dermatology. Dermatol Surg 2005; 31(7 PT 2):805-13; discussion 813.
47. Niki E. Evidence for beneficial effects of vitamin E. Korean J Intern Med 2015; 30(5):571-9.
48. Niki E. Role of vitamin E as a lipid-soluble peroxyl radical scavenger: in vitro and in vivo evidence. Free Radic Biol Med 2014; 66:3-12.
49. Schagen SK, Zampeli VA, Makrantonaki E, Zouboulis CC. Discovering the link between nutrition and skin aging. Dermatoendocrinol 2012; 4(3):298-307.
50. Dattola A, Silvestri M, Bennardo L, Passante M, Scali E, Patruno C, et al. Role of vitamins in skin health: a systematic review. Curr Nutr Rep 2020; 9(3):226-35.
51. Zondlo Fiume M. Final report on the safety assessment of tocopherol, tocopheryl acetate, tocopheryl linoleate, tocopheryl linoleate/oleate, tocopheryl nicotinate, tocopheryl succinate, dioleyl tocopheryl methylsilanol, potassium ascorbyl tocopheryl phosphate, and tocophersolan. Int J Toxicol 2002; 21 Suppl 3:51-116.
52. Ganceviciene R, Liakou AI, Theodoridis A, Makrantonaki E, Zouboulis CC. Skin anti-aging strategies. Dermatoendocrinol 2012; 4(3):308-19.
53. Gorouhi F, Maibach HI. Role of topical peptides in preventing or treating aged skin. Int J Cosmet Sci 2009; 31(5):327-45.
54. Errante F, Ledwoń P, Latajka R, Rovero P, Papini AM. Cosmeceutical peptides in the framework of sustainable wellness economy. Front Chem 2020; 8:572923.
55. Schagen SK. Topical peptide treatments with effective anti-aging results. Cosmetics 2017; 4(2):16.
56. Lima TN, Pedriali Moraes CA. Bioactive peptides: applications and relevance for cosmeceuticals. Cosmetics 2018; 5(1):21.
57. Kumari S, Panda TK, Pradhan T. Lysyl oxidase: its diversity in health and diseases. Indian J Clin Biochem 2017; 32:134-41.
58. Wang X, Khalil RA. Matrix metalloproteinases, vascular remodeling, and vascular disease. Adv Pharmacol 2018; 81:241-330.
59. Pittayapruek P, Meephansan J, Prapapan O, Komine M, Ohtsuki M. Role of matrix metalloproteinases in photoaging and photocarcinogenesis. Int J Mol Sci 2016; 17(6):868.
60. Tran D, Townley JP, Barnes TM, Greive KA. An antiaging skin care system containing alpha hydroxy acids and vitamins improves the biomechanical parameters of facial skin. Clin Cosmet Investig Dermatol 2015; 8:9-17.
61. Tang SC, Yang JH. Dual effects of alpha-hydroxy acids on the skin. Molecules 2018; 23(4):863.
62. Parker ET, Cleaves HJ, Bada JL, Fernández FM. Quantitation of α-hydroxy acids in complex prebiotic mixtures via liquid chromatography/tandem mass spectrometry. Rapid Commun Mass Spectrom 2016; 30(18):2043-51.
63. Kornhauser A, Coelho SG, Hearing VJ. Applications of hydroxy acids: classification, mechanisms, and photoactivity. Clin Cosmet Investig Dermatol 2010; 3:135-42.
64. Green B. After 30 years … the future of hydroxyacids. J Cosmet Dermatol 2005; 4(1):44-5.
65. Boo YC. Mechanistic basis and clinical evidence for the applications of nicotinamide (niacinamide) to control skin aging and pigmentation. Antioxidants 2021; 10(8):1315.
66. Chambers ES, Vukmanovic-Stejic M. Skin barrier immunity and ageing. Immunology 2020; 160(2):116-25.
67. Bains P, Kaur M, Kaur J, Sharma S. Nicotinamide: mechanism of action and indications in dermatology. Indian J Dermatol Venereol Leprol 2018; 84(2):234-7.
68. Wohlrab J, Kreft D. Niacinamide - Mechanisms of Action and Its Topical Use in Dermatology. Skin Pharmacol Physiol 2014; 27(6):311-5.
69. Esfahani SA, Khoshneviszadeh M, Namazi MR, Noorafshan A, Geramizadeh B, Nadimi E, et al. Topical nicotinamide improves tissue regeneration in excisional full-thickness skin wounds: a stereological and pathological study. Trauma Mon 2015; 20(4):18193.
70. Shariff R, Du Y, Dutta M, Kumar S, Thimmaiah S, Doraiswamy C, et al. Superior even skin tone and anti-ageing benefit of a combination of 4-hexylresorcinol and niacinamide. Int J Cosmet Sci 2022; 44(1):103-17.
71. Snaidr VA, Damian DL, Halliday GM. Nicotinamide for photoprotection and skin cancer chemoprevention: a review of efficacy and safety. Exp Dermatol 2019; 28 Suppl 1:15-22.
72. Krutmann J, Liu W, Li L, Pan X, Crawford M, Sore G, et al. Pollution and skin: from epidemiological and mechanistic studies to clinical implications. J Dermatol Sci 2014; 76(3):163-8.
73. Yoshizumi M, Nakamura T, Kato M, Ishioka T, Kozawa K, Wakamatsu K, et al. Release of cytokines/chemokines and cell death in UVB-irradiated human keratinocytes, HaCaT. Cell Biol Int 2008; 32(11):1405-11.
74. Camillo L, Gironi LC, Zavattaro E, Esposto E, Savoia P. Nicotinamide attenuates uv-induced stress damage in human primary keratinocytes from cancerization fields. J Invest Dermatol 2022; 142(5):1466-77.e1.
75. Puri P, Nandar SK, Kathuria S, Ramesh V. Effects of air pollution on the skin: a review. Indian J Dermatol Venereol Leprol 2017; 83(4):415-23.
76. Buranasudja V, Rani D, Malla A, Kobtrakul K, Vimolmangkang S. Insights into antioxidant activities and anti-skin-aging potential of callus extract from Centella asiatica (L.). Sci Rep 2021; 11(1):13459.
77. Gu Y, Han J, Jiang C, Zhang Y. Biomarkers, oxidative stress and autophagy in skin aging. Ageing Res Rev 2020; 59:101036.
78. Tungmunnithum D, Thongboonyou A, Pholboon A, Yangsabai A. Flavonoids and other phenolic compounds from medicinal plants for pharmaceutical and medical aspects: an overview. Medicines 2018; 5(3):93.
79. Michalak M, Pierzak M, Kręcisz B, Suliga E. Bioactive compounds for skin health: a review. Nutrients 2021; 13(1):203.
80. Silva S, Ferreira M, Oliveira AS, Magalhães C, Sousa ME, Pinto M, et al. Evolution of the use of antioxidants in anti-ageing cosmetics. Int J Cosmet Sci 2019; 41(4):378-86.
81. Cai Z, Zhang J, Li H. Selenium, aging and aging-related diseases. Aging Clin Exp Res 2019; 31(8):1035-47.
82. Tuong W, Walker L, Sivamani RK. Polyphenols as novel treatment options for dermatological diseases: a systematic review of clinical trials. J Dermatol Treat 2015; 26(4):381-8.
83. Shahidi F, Ambigaipalan P. Phenolics and polyphenolics in foods, beverages and spices: Antioxidant activity and health effects – A review. J Funct Foods 2015; 18:820-97.
84. Pullar JM, Carr AC, Vissers MCM. The Roles of Vitamin C in Skin Health. Nutrients 2017; 9(8):866.
85. Addor FAS. Antioxidants in dermatology. An Bras Dermatol 2017; 92(3):356-62.

Article Metrics

Abstract views : 535 | views : 831

Copyright (c) 2024 Flora Ramona Sigit Prakoeswa, Faradiba Maharani, Yohanes Aditya Adhi Satria, Ghina Shabrina Awanis, Astrida Fesky Febrianty

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

View My Stats


Creative Commons License
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) by  Universitas Gadjah Mada is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Based on a work at