Sadra Medical Journal

Bioactive Peptides in Skin Rejuvenation: A Review of Classifications, Marine Sources, and Molecular Mechanisms

Articles in Press

Document Type : Review Article

Authors

Sheyda Mirzaei 1, 2
Mohammad Hossein Morowvat 2, 3

1 Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran

2 Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

3 Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

10.30476/smsj.2026.110509.1755
Abstract
Skin aging is a complex biological process driven by intrinsic and extrinsic factors that inevitably leads to progressive degradation of the extracellular matrix, wrinkle formation, and a significant loss of elasticity. Although conventional anti-aging interventions, such as retinoids and laser therapies, are effective, they are frequently associated with adverse effects such as skin irritation and prolonged recovery periods. Consequently, there is a growing demand for safer, non-invasive alternatives. This review article comprehensively examined the therapeutic potential of bioactive peptides in cosmeceuticals. We analyzed their classification into signal, carrier, and neurotransmitter-inhibiting peptides, elucidating their specific mechanisms in stimulating collagen synthesis and modulating neuromuscular transmission. The findings demonstrated that these peptides effectively mimicked natural biological signals to repair damaged skin structure while maintaining high biocompatibility. By providing a targeted approach, they successfully overcame the limitations of traditional therapies. Ultimately, bioactive peptides represented a promising frontier in dermatology, offering a potent yet safe strategy for skin rejuvenation and the mitigation of age-related cutaneous changes.

Keywords

Collagen
Cosmetics
Extracellular matrix
Peptides
Skin aging
  1. Tenchov R, Sasso JM, Wang X, Zhou QA. Aging hallmarks and progression and age-related diseases: a landscape view of research advancement. ACS Chem Neurosci. 2024;15(1):1-30.
  2. López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. Hallmarks of aging: an expanding universe. Cell. 2023;186(2):243-78.
  3. Abo Qoura L, Churov AV, Maltseva ON, Arbatskiy MS, Tkacheva ON. The aging interactome: from cellular dysregulation to therapeutic frontiers in age-related diseases. Biochim Biophys Acta Mol Basis Dis. 2026;1872(1):168060.
  4. Cerrato G, Sauvat A, Peyre F, Kepp O, Kroemer G. High-throughput assessment of cellular senescence. Methods Cell Biol. 2024;181:151-60.
  5. Wang Z, Ge S, Liao T, Yuan M, Qian W, Chen Q, et al. Integrative single-cell metabolomics and phenotypic profiling reveals metabolic heterogeneity of cellular oxidation and senescence. Nat Commun. 2025;16(1):2740.
  6. World Health Organization. Ageing and health. Geneva: WHO; 2022.
  7. United Nations Department of Economic and Social Affairs. World population prospects 2022: summary of results. New York: United Nations; 2022.
  8. United Nations Population Fund. Ageing in Iran: demographic trends and policy implications. Tehran: UNFPA Iran Country Office; 2023.
  9. World Bank. World development indicators: Iran—population growth and fertility. Washington: World Bank Group; 2022.
  10. Furman D, Auwerx J, Bulteau AL, Church G, Couturaud V, Crabbé L, et al. Skin health and biological aging. Nat Aging. 2025;5(7):1195-206.
  11. Sriram R, Gopal V. Mechanistic insights on skin ageing and dermatologic interventions to slow ageing process. Indian J Dermatol. 2025;70(3):135-45.
  12. Thau H, Gerjol BP, Hahn K, von Gudenberg RW, Knoedler L, Stallcup K, et al. Senescence as a molecular target in skin aging and disease. Ageing Res Rev. 2025;105:102686.
  13. Tabata Y. Geranylgeranoic acid and the MAOB–CYP3A4 axis: a metabolic shift underlying age-related liver cancer risk. Front Aging. 2025;6:1680031.
  14. Zhang M, Ni H, Lin Y, Wang K, He T, Yuan L, et al. Renal aging and its consequences: navigating the challenges of an aging population. Front Pharmacol. 2025;16:123456.
  15. Bonanno EG, Figueiredo T, Mimoso IF, Morgado MI, Carrilho J, Midão L, et al. Polypharmacy prevalence among older adults based on the survey of health, ageing and retirement in Europe: an update. J Clin Med. 2025;14(4):321.
  16. Asaoka S, Shimbashi T. Skin rejuvenation using fractional radio frequency. Jpn J Plast Reconstr Surg. 2015;58(7):753-60.
  17. Scarcella G, Pennati BM. A temperature-controlled radio frequency combined with ultrasounds and laser for skin laxity and cellulitis. SAGE Open Med Case Rep. 2024;12:20503121241234567.
  18. Verner I, Kutscher TD. Clinical evaluation of the efficacy and safety of combined bipolar radiofrequency and optical energies vs. optical energy alone for the treatment of aging hands. Lasers Med Sci. 2017;32(6):1387-92.
  19. Sorg O, Saurat JH. Topical retinoids in skin ageing: a focused update with reference to sun-induced epidermal vitamin A deficiency. Dermatology. 2014;228(4):314-25.
  20. Zasada M, Budzisz E. Retinoids: active molecules influencing skin structure formation in cosmetic and dermatological treatments. Postepy Dermatol Alergol. 2019;36(4):392-7.
  21. Eassa HA, Eltokhy MA, Fayyaz HA, Khalifa MKA, Shawky S, Helal NA, et al. Current topical strategies for skin-aging and inflammaging treatment: science versus fiction. J Cosmet Sci. 2020;71(5):321-50.
  22. Conti V, Izzo V, Corbi G, Russomanno G, Manzo V, De Lise F, et al. Antioxidant supplementation in the treatment of aging-associated diseases. Front Pharmacol. 2016;7:421.
  23. Xiong Y, Wu M, Hou X, Chen H, Tang H. Lipidated peptide nanostructures for stabilizing hydrogels with sustained skincare bioactivity. J Control Release. 2026;389:114567.
  24. Amin R, Rancan F, Hillmann K, Blume-Peytavi U, Vogt A, Kottner J. Effects of a leave-on product on the strength of the dermoepidermal junction: an exploratory, intraindividual, randomized controlled trial in older adults with dry skin. Health Sci Rep. 2024;7(3):e1987.
  25. Fluhr JW, Muguet V, Christen-Zaech S. Restoring skin hydration and barrier function: mechanistic insights into basic emollients for xerosis cutis. Int J Dermatol. 2025;64(Suppl 1):5-12.
  26. Sunder S. Relevant topical skin care products for prevention and treatment of aging skin. Facial Plast Surg Clin North Am. 2019;27(3):413-8.
  27. Griffiths TW, Watson REB, Langton AK. Skin ageing and topical rejuvenation strategies. Br J Dermatol. 2023;189(1):117-23.
  28. Pintea A, Manea A, Pintea C, Vlad RA, Birsan M, Antonoaea P, et al. Peptides: emerging candidates for the prevention and treatment of skin senescence: a review. Biomolecules. 2025;15(1):123.
  29. Schagen SK. Topical peptide treatments with effective anti-aging results. Cosmetics. 2017;4(2):16.
  30. Blanes-Mira C, Clemente J, Jodas G, Gil A, Fernández-Ballester G, Ponsati B, et al. A synthetic hexapeptide (Argireline) with antiwrinkle activity. Int J Cosmet Sci. 2002;24(5):303-10.
  31. Moradi A, Bhatia AC, Behr K, Napekoski K, Foldvari M. In vivo and ex vivo evaluation of a novel method for topical delivery of macromolecules through the stratum corneum for cosmetic applications. Dermatol Surg. 2025;51(4):403-8.
  32. Suter F, Schmid D, Wandrey F, Zülli F. Heptapeptide-loaded solid lipid nanoparticles for cosmetic anti-aging applications. Eur J Pharm Biopharm. 2016;108:304-9.
  33. Ngoc LTN, Moon JY, Lee YC. Insights into bioactive peptides in cosmetics. Cosmetics. 2023;10(4):98.
  34. Lima TN, Pedriali Moraes CA. Bioactive peptides: applications and relevance for cosmeceuticals. Cosmetics. 2018;5(1):12.
  35. Robinson LR, Fitzgerald NC, Doughty DG, Dawes NC, Berge CA, Bissett DL. Topical palmitoyl pentapeptide provides improvement in photoaged human facial skin. Int J Cosmet Sci. 2005;27(3):155-60.
  36. Aldag C, Nogueira Teixeira D, Leventhal PS. Skin rejuvenation using cosmetic products containing growth factors, cytokines, and matrikines: a review of the literature. Clin Cosmet Investig Dermatol. 2016;9:411-9.
  37. Pickart L, Margolina A. Skin regenerative and anti-cancer actions of copper peptides. Cosmetics. 2018;5(2):28.
  38. Pyun HB, Kim M, Park J, Sakai Y, Numata N, Shin JY, et al. Effects of collagen tripeptide supplement on photoaging and epidermal skin barrier in UVB-exposed hairless mice. Prev Nutr Food Sci. 2012;17(4):245-53.
  39. van Walraven N, FitzGerald RJ, Danneel HJ, Amigo-Benavent M. Bioactive peptides in cosmetic formulations: review of current in vitro and ex vivo evidence. Peptides. 2025;193:171440.
  40. Pickart L, Margolina A. Regenerative and protective actions of the GHK-Cu peptide in the light of the new gene data. Int J Med Sci. 2018;15(7):685-707.
  41. Gorouhi F, Maibach HI. Role of topical peptides in preventing or treating aged skin. Int J Cosmet Sci. 2009;31(5):327-45.
  42. Husein El Hadmed H, Castillo RF. Cosmeceuticals: peptides, proteins, and growth factors. J Cosmet Dermatol. 2016;15(4):514-9.
  43. Burnett CL, Boyer IJ, Bergfeld WF, Belsito DV, Hill RA, Klaassen CD, et al. Safety assessment of plant-derived proteins and peptides as used in cosmetics. Int J Toxicol. 2022;41(2 Suppl):5-20.
  44. Hou J, Wei W, Geng Z, Zhang Z, Yang H, Zhang X, et al. Developing plant exosomes as an advanced delivery system for cosmetic peptide. ACS Appl Bio Mater. 2024;7(5):3050-60.
  45. Lafarga T, Sánchez-Zurano A, Villaró-Cos S, Morillas-España A, Acién G. Industrial production of Spirulina as a protein source for bioactive peptide generation. Trends Food Sci Technol. 2021;116:176-85.
  46. Masoumifeshani B, Abedian Kenari A, Sottorff I, Crüsemann M, Amiri Moghaddam J. Identification and evaluation of antioxidant and anti-aging peptide fractions from enzymatically hydrolyzed proteins of Spirulina platensis and Chlorella vulgaris. Mar Drugs. 2025;23(4):210.
  47. Badilli U, İnal O. Current approaches in cosmeceuticals: peptides, biotics and marine biopolymers. Polymers (Basel). 2025;17(6):987.
  48. Cunha SA, Pintado ME. Bioactive peptides derived from marine sources: biological and functional properties. Trends Food Sci Technol. 2022;119:348-70.
  49. Ram KH, Selvi BT. Inventive applications of marine resources in cosmetic production: a review. In: Multidisciplinary applications of marine resources. Singapore: Springer Nature; 2024. p. 407-41.
  50. Thathola P, Haldar S. Marine invertebrates antioxidant proteins, peptides and their biofunctionalities. In: Sarma H, Joshi S, Kumar MS, Daverey A, Joshi S, Buttar HS, editors. Marine biotechnology for healthcare. Amsterdam: Elsevier; 2025. p. 173-86.
  51. Bravo B, Correia P, Gonçalves Junior JE, Sant’Anna B, Kerob D. Benefits of topical hyaluronic acid for skin quality and signs of skin aging: from literature review to clinical evidence. Dermatol Ther. 2022;35(12):e15903.
  52. Zaid AN, Al Ramahi RA. Depigmentation and anti-aging treatment by natural molecules. Curr Pharm Des. 2019;25(20):2292-312.
  53. Chavda VP, Acharya D, Hala V, Daware S, Vora LK. Sunscreens: a comprehensive review with the application of nanotechnology. J Drug Deliv Sci Technol. 2023;86:104720.
  54. Abendrot M, Płuciennik E, Felczak A, Zawadzka K, Piątczak E, Nowaczyk P, et al. Zinc (II) complexes of amino acids as new active ingredients for anti-acne dermatological preparations. Int J Mol Sci. 2021;22(4):1890.
  55. Zhang L, Dong Z, Liu W, Wu X, He H, Lu Y, et al. Novel pharmaceutical strategies for enhancing skin penetration of biomacromolecules. Pharmaceuticals (Basel). 2022;15(7):842.
  56. Li S, Liu Y, Wu Y, Ren L, Lu Y, Yamaguchi S, et al. An outlook on platinum-based active ingredients for dermatologic and skincare applications. Nanomaterials (Basel). 2024;14(15):1234.
  57. Lekhavadhani S, Babu S, Shanmugavadivu A, Selvamurugan N. Advances in magnesium-incorporated polymeric scaffolds: a next-generation strategy for enhanced wound healing. J Magnes Alloys. 2026;14:101931.
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Available Online from 29 August 2026

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