Abstract

Research Article

In vitro beneficial effects of a flax extract on papillary fibroblasts define it as an anti-aging candidate

PAGEON Hervé*, ZUCCHI Hélène, RICOIS Sylvie, BASTIEN Philippe and ASSELINEAU Daniel

Published: 05 May, 2021 | Volume 5 - Issue 1 | Pages: 032-040

Objective: During aging, skin undergoes structural, cellular and molecular changes, which not only alter skin mechanical properties but also biological and physiological functions. Structurally the epidermis becomes thinner, the dermal epidermal junction flattens and the extra-cellular matrix component of the dermis is disorganized and degraded. The dermis is composed of two compartments: The Reticular dermis is the deepest and thickest part while the upper layer, the papillary dermis, which is much thinner and is in close contact with epidermis, plays an important role in the structure and function of the skin. We have recently shown that the papillary dermis was preferentially affected by skin aging because the activity of fibroblasts in this region was especially altered as a function of age. The purpose of this study was to investigate the capacity of a flax extract as anti-aging component.

Method: We investigated the capacity of a flax extract to stimulate or restore the activity of papillary fibroblasts from young and old donors in cultured monolayers and in reconstructed skin. Several biological markers of extracellular matrix homeostasis and mechanical properties were investigated.

Results: The tested flax extract seemed to improve parameters known to change with age: I/ In monolayers after treatment the number of aged fibroblasts increased II/ In reconstructed skin the flax extract appears to positively regulate some biological activities; particularly in aged fibroblasts where the deposition of laminin 5, fibrillin 1, procollagen I were increased in the dermis and the secretion of specific soluble factors like MMP1, MMP3 and KGF were regulated to levels similar to those observed in young fibroblasts III/ Mechanical properties were improved particularly for elastics parameters (R5, R2 and R7).

Conclusion: The flax extract is a promising anti-aging compound. The treatment of aged papillary fibroblasts resulted in a return to a younger-like profile for some of the studied parameters.

Read Full Article HTML DOI: 10.29328/journal.abb.1001026 Cite this Article Read Full Article PDF

Keywords:

Cell culture; Skin physiology; Flax-extract; Skin aging; Fibroblasts; Mechanical properties

References

  1. Zouboulis CC, Makrantonaki E. Clinical aspects and molecular diagnostics of skin aging. Clin Dermatol. 2011; 29: 3-14. PubMed: https://pubmed.ncbi.nlm.nih.gov/21146726/
  2. Kanaki T, Makrantonaki E, Zouboulis C. Biomarkers of skin aging. Rev Endocr Metab Disord. 2016; 17: 433-442. PubMed: https://pubmed.ncbi.nlm.nih.gov/27830493/
  3. Weber L, Kirsch E, Muller P, Krieg T. Collagen type distribution and macromolecular organization of connective tissue in different layers of human skin. J Invest Dermatol. 1984; 82: 156-160. PubMed: https://pubmed.ncbi.nlm.nih.gov/6693779/
  4. Zimmermann DR, Dours-Zimmermann MT, Schubert M, Bruckner-Tuderman,L. Versican is expressed in the proliferating zone in the epidermis and in association with the elastic network of the dermis. J Cell Biol. 1994; 124: 817-825. PubMed: https://pubmed.ncbi.nlm.nih.gov/8120102/
  5. Sorrell JM, Caplan AI. Fibroblast heterogeneity: more than skin deep. J Cell Sci. 2004a; 117: 667-675. PubMed: https://pubmed.ncbi.nlm.nih.gov/14754903/
  6. Pageon H, Zucchi H, Asselineau D. Distinct and complementary roles of papillary and reticular fibroblasts in skin morphogenesis and homeostasis. Eur J Dermatol. 2012; 22: 324-332. PubMed: https://pubmed.ncbi.nlm.nih.gov/22449755/
  7. Mine S, Fortunel NO, Pageon H, Asselineau D. Aging alters functionally human dermal papillary fibroblasts but not reticular fibroblasts: a new view of skin morphogenesisand aging. PLoS ONE. 2008; 3: e4066. PubMed: https://pubmed.ncbi.nlm.nih.gov/19115004/
  8. Varani J, Warner RL, Gharaee-Kermani M, Phan SH, Kang S, 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; 114: 480–486. PubMed: https://pubmed.ncbi.nlm.nih.gov/10692106/
  9. Nusgens BV, Humbert P, Rougier A, Colige AC, Haftek M, et al. Topically applied vitamin C enhances the mRNA level of collagens I and III, their processing enzymes and tissue inhibitor of matrix metalloproteinase I in the human dermis. J Invest Dermatol. 2001; 116: 853–859. PubMed: https://pubmed.ncbi.nlm.nih.gov/11407971/
  10. Asselineau D, Bernard BA, Bailly C, Darmon M. Retinoic acid improves epidermal morphogenesis. Dev Biol 1989; 133: 322–335. PubMed: https://pubmed.ncbi.nlm.nih.gov/2471653/
  11. Phillips CL, Combs SB, Pinnell SR. Effects of ascorbic acid proliferation and collagen synthesis in relation to the donor age of human dermal fibroblasts. J Invest Dermatol. 1994; 103: 228–232. PubMed: https://pubmed.ncbi.nlm.nih.gov/7518857/
  12. Marionnet C, Vioux-Chagnoleau C, Pierrard C, Sok J, Asselineau D, et al. Morphogenesis of dermal epidermal junction in a model of reconstructed skin: beneficial effect of vitamin C. Exp Dermatol. 2006; 15: 625–633. PubMed: https://pubmed.ncbi.nlm.nih.gov/16842601/
  13. Pageon H, Azouaoui A, Zucchi H, Ricois S, Tran C, et al. Potentially beneficial effects of rhamnose on skin ageing: an in vitro and in vivo study. Int J Cosmet Sci. 2019; 41: 213-220. PubMed: https://pubmed.ncbi.nlm.nih.gov/30845349/
  14. Rheinwald JG, Green H. Serial cultivation of strains of human epidermal keratinocytes: the formation of keratinizing colonies from single cells. Cell. 1975; 6: 331-343. PubMed: https://pubmed.ncbi.nlm.nih.gov/1052771/
  15. Asselineau D, Prunieras M. Reconstruction of simplified skin: control of fabrication. Br J Dermatol. 1984; 111: 219–222. PubMed: https://pubmed.ncbi.nlm.nih.gov/6743553/
  16. Asselineau D, Bernhard B, Bailly C, Darmon M. Epidermal morphogenesis and induction of the 67 kD keratin polypeptide by culture of human keratinocytes at the liquid-air interface. Exp Cell Res. 1985; 159: 536-539. PubMed: https://pubmed.ncbi.nlm.nih.gov/2411581/
  17. Battie C, Verschoore M. Cutaneous solar ultraviolet exposure and clinical aspects of photodamage. Indian J Dermatol Venereol Leprol. 2012; 78/S9-S14. PubMed: https://pubmed.ncbi.nlm.nih.gov/22710112/
  18. Lago JC, Puzzi MB. The effect of aging in primary human dermal fibroblasts. PLoS One. 2019; 14: e0219165. PubMed: https://pubmed.ncbi.nlm.nih.gov/31269075/
  19. Verma RP, Hansch C. Matrix metalloproteinases (MMPs): Chemical-biological functions and (Q)SARS. Bioorg Med Chem. 2007; 15: 2223–2268. PubMed: https://pubmed.ncbi.nlm.nih.gov/17275314/
  20. Quan T, Little E, Quan H, Qin Z, Voorhees JJ, et al. Elevated matrix metalloproteinases and collagen fragmentation in photodamaged human skin: impact of altered extracellular matrix microenvironment on dermal fibroblast function. J Invest Dermatol. 2013; 133: 1362‐1366. PubMed: https://pubmed.ncbi.nlm.nih.gov/23466932/
  21. Brennan M, Bhatti H, Nerusu KC, Bhagavathula N, Kang S, Fisher GJ, et al. Matrix metalloproteinase-1 is the major collagenolytic enzyme responsible for collagen damage in uv-irradiated human skin. Photochem Photobiol. 2003; 78: 43–48. PubMed: https://pubmed.ncbi.nlm.nih.gov/12929747/
  22. Varani J, Dame MK, Rittie L, Fligiel SE, Kang S, et al. Decreased collagen production in chronologically aged skin: roles of age-dependent alteration in fibroblast function and defective mechanical stimulation. Am J Pathol. 2006; 168: 1861–1868. PubMed: https://pubmed.ncbi.nlm.nih.gov/16723701/
  23. Quan C, Cho MK, Perry D, Quan T. Age-associated reduction of cell spreading induces mitochondrial DNA common deletion by oxidative stress in human skin dermal fibroblasts: implication for human skin connective tissue aging. J Biomed Sci. 2015; 22: 62. PubMed: https://pubmed.ncbi.nlm.nih.gov/26215577/
  24. Beylot C. Skin aging: clinico pathological features and mechanisms. Annales de Dermatologie. 2009; 136: S263-S269. PubMed: https://pubmed.ncbi.nlm.nih.gov/19931682/
  25. Oh JH, Kim YK, Jung JY, Shin JE, Chung JH. Changes in glycosaminoglycans and related proteoglycans in intrinsically aged human skin in vivo. Exp. Dermatol. 2011; 20: 454–456. PubMed: https://pubmed.ncbi.nlm.nih.gov/21426414/
  26. Lee DH, Oh JH, Chung JH. Glycosaminoglycan and proteoglycan in skin aging. J Dermatol Sci. 2016; 83: 174-181. PubMed: https://pubmed.ncbi.nlm.nih.gov/27378089/
  27. Deloche C, Minondo AM, Bernard BA, Bernerd F, Salas F, et al. Effect of C-xyloside on morphogenesis of the dermal epidermal junction in aged female skin. An ultrastuctural pilot study. Eur. J Dermatol. 2011; 21: 191–196. PubMed: https://pubmed.ncbi.nlm.nih.gov/21454149/
  28. Langton AK, Halai P, Griffiths CE, Sherratt MJ, Watson RE. The impact of intrinsic ageing on the protein composition of the dermal-epidermal junction. Mech Ageing Dev. 2016; 156:14-16. PubMed: https://pubmed.ncbi.nlm.nih.gov/27013376/
  29. Gibbs S, Silva Pinto AN, Murli S, Huber M, Hohl D, et al. Epidermal growth factor and keratinocyte growth factor differentially regulate epidermal migration, growth, and differentiation. Wound Repair Regen. 2000; 8: 192–203. PubMed: https://pubmed.ncbi.nlm.nih.gov/10886810/
  30. Krueger N, Luebberding S, Oltmer M, Streker M, Kerscher M. Age-related changes in skin mechanical properties: a quantitative evaluation of 120 female subjects. Skin Res Technol. 2011; 17: 141-148. PubMed: https://pubmed.ncbi.nlm.nih.gov/21281361/
  31. Fisher GJ, Quan T, Purohit T, Shao Y, Cho MK, et al. Collagen fragmentation promotes oxidative stress and elevates matrix metalloproteinase-1 in fibroblasts in aged human skin. Am J Pathol. 2009; 174: 101‐114. PubMed: https://pubmed.ncbi.nlm.nih.gov/19116368/
  32. Fisher GJ, Shao Y, He T, Qin Z, Perry D, et al. Reduction of fibroblast size/mechanical force down-regulates TGF-β type II receptor: implications for human skin aging. Aging Cell. 2016; 15: 67‐76. PubMed: https://pubmed.ncbi.nlm.nih.gov/26780887/
  33. Quan T, Fisher GJ. Role of Age-Associated Alterations of the Dermal Extracellular Matrix Microenvironment in Human Skin Aging: A Mini-Review. Gerontology. 2015; 61: 427‐434. PubMed: https://pubmed.ncbi.nlm.nih.gov/25660807/
  34. Qin Z, Balimunkwe RM, Quan T. Age-related reduction of dermal fibroblast size upregulates multiple matrix metalloproteinases as observed in aged human skin in vivo. Br J Dermatol. 2017; 177: 1337‐1348. PubMed: https://pubmed.ncbi.nlm.nih.gov/28196296/
  35. Yutskovskaya YA, Kogan EA. Improved Neocollagenesis and Skin Mechanical Properties After Injection of Diluted Calcium Hydroxylapatite in the Neck and Décolletage: A Pilot Study. J Drugs Dermatol. 2017; 16: 68‐74. PubMed: https://pubmed.ncbi.nlm.nih.gov/28095536/
  36. Beroual K, Agabou A, Abdeldjelil MC, Boutaghane N, Haouam S, et al. Evaluation of crude flaxeed (Linum usitatissimum L) oil in burn wound healing in new zealand rabbits. Afr J Tradit Complement Altern Med. 2017; 14: 280-286. PubMed: https://pubmed.ncbi.nlm.nih.gov/28480439/
  37. Stahl W, Sies H. β-Carotene and other carotenoids in protection from sunlight. Am J Clin Nutr. 2012; 96: 1179S-1184S. PubMed: https://pubmed.ncbi.nlm.nih.gov/23053552/
  38. Bose S, Munsch T, Lanoue A, Garros L, Tungmunnithum D, et al. UPLC-HRMS Analysis Revealed the Differential Accumulation of Antioxidant and Anti-Aging Lignans and Neolignans in In Vitro Cultures of Linum usitatissimum L. Front Plant Sci. 2020; 11: 508658. PubMed: https://pubmed.ncbi.nlm.nih.gov/33072140/

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