Skip to main content

Advertisement

SpringerLink
Log in

Modeling human gray hair by irradiation as a valuable tool to study aspects of tissue aging

  • Original Article
  • Published:
GeroScience Aims and scope Submit manuscript

Abstract

As one of the earliest and most visible phenomenon of aging, gray hair makes it a unique model system for investigating the mechanism of aging. Ionizing radiation successfully induces gray hair in mice, and also provides a venue to establish an organ-cultured human gray hair model. To establish a suitable organ-cultured human gray HF model by IR, which imitates gray hair in the elderly, and to explore the mechanisms behind the model. By detecting growth parameters, melanotic and senescence markers of the model, we found that the model of 5 Gy accords best with features of elderly gray hair. Then, we investigated the formation mechanisms of the model by RNA-sequencing. We demonstrated that the model of organ-cultured gray HFs after 5 Gy irradiation is closest to the older gray HFs. Moreover, the 5 Gy inhibited the expression of TRP-1, Tyr, Pmel17, and MITF in hair bulbs/ORS of HFs. The 5 Gy also significantly induced ectopically pigmented melanocytes and increased the expression of DNA damage and senescence in HFs. Finally, RNA-seq analysis of the model suggested that IR resulted in cell DNA damage, and the accumulation of oxidative stress in the keratinocytes. Oxidative stress and DNA damage caused cell dysfunction and decreased melanin synthesis in the gray HFs. We found that HFs irradiated at 5 Gy successfully constructed an appropriate aging HF model. This may provide a useful model for cost-effective and predictable treatment strategies to human hair graying and the process of aging.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Data availability

The data that support the findings of this study have been deposited in Gene Expression Omnibus with the accession code: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi.acc=GSE193386.

References

  1. Panhard S, Lozano I, Loussouarn G. Greying of the human hair: a worldwide survey, revisiting the “50” rule of thumb. Br J Dermatol. 2012;167:865–73.

    Article  CAS  Google Scholar 

  2. Keogh EV, Walsh RJ. Rate of greying of human hair. Nature. 1965;207:877–8.

    Article  CAS  Google Scholar 

  3. Mendelsohn AR, Larrick JW. The Danger of Being Too Sympathetic: Norepinephrine in Alzheimer’s Disease and Graying of Hair. Rejuvenation Res. 2020;23:68–72.

    Article  CAS  Google Scholar 

  4. Juceviciute N, Banaityte I, Vaitkus A, Balnyte R. Preclinical signs of Parkinson’s disease: A possible association of Parkinson’s disease with skin and hair features. Med Hypotheses. 2019;127:100–4.

    Article  Google Scholar 

  5. ElFaramawy AAA, Hanna IS, Darweesh RM, Ismail AS, Kandil HI. The degree of hair graying as an independent risk marker for coronary artery disease, a CT coronary angiography study. Egypt Heart J. 2018;70:15–9.

    Article  Google Scholar 

  6. Nishimura EK, Granter SR, Fisher DE. Mechanisms of hair graying: incomplete melanocyte stem cell maintenance in the niche. Science. 2005;307:720–4.

    Article  CAS  Google Scholar 

  7. Nishimura EK. Melanocyte stem cells: a melanocyte reservoir in hair follicles for hair and skin pigmentation. Pigment Cell Melanoma Res. 2011;24:401–10.

    Article  CAS  Google Scholar 

  8. Commo S, Gaillard O, Bernard BA. Human hair greying is linked to a specific depletion of hair follicle melanocytes affecting both the bulb and the outer root sheath. Br J Dermatol. 2004;150:435–43.

    Article  CAS  Google Scholar 

  9. Inomata K, et al. Genotoxic stress abrogates renewal of melanocyte stem cells by triggering their differentiation. Cell. 2009;137:1088–99.

    Article  CAS  Google Scholar 

  10. Zhang B, et al. Hyperactivation of sympathetic nerves drives depletion of melanocyte stem cells. Nature. 2020;577:676–81.

    Article  CAS  Google Scholar 

  11. Riley T, Sontag E, Chen P, Levine A. Transcriptional control of human p53-regulated genes. Nat Rev Mol Cell Biol. 2008;9:402–12.

    Article  CAS  Google Scholar 

  12. Aoki H, Hara A, Motohashi T, Kunisada T. Keratinocyte stem cells but not melanocyte stem cells are the primary target for radiation-induced hair graying. J Invest Dermatol. 2013;133:2143–51.

    Article  CAS  Google Scholar 

  13. Oh JW, et al. A Guide to Studying Human Hair Follicle Cycling In Vivo. J Invest Dermatol. 2016;136:34–44.

    Article  CAS  Google Scholar 

  14. Rachmin I, et al. Stress-associated ectopic differentiation of melanocyte stem cells and ORS amelanotic melanocytes in an ex vivo human hair follicle model. Exp Dermatol. 2021;30:578–87.

    Article  CAS  Google Scholar 

  15. Arck PC, et al. Towards a “free radical theory of graying”: melanocyte apoptosis in the aging human hair follicle is an indicator of oxidative stress induced tissue damage. FASEB J. 2006;20:1567–9.

    Article  CAS  Google Scholar 

  16. Peters EM, et al. Profiling mRNA of the graying human hair follicle constitutes a promising state-of-the-art tool to assess its aging: an exemplary report. J Invest Dermatol. 2013;133:1150–60.

    Article  CAS  Google Scholar 

  17. Poeggeler B, Bodo E, Nadrowitz R, Dunst J, Paus R. A simple assay for the study of human hair follicle damage induced by ionizing irradiation. Exp Dermatol. 2010;19:e306-309.

    Article  Google Scholar 

  18. Van Neste D, Tobin DJ. Hair cycle and hair pigmentation: dynamic interactions and changes associated with aging. Micron. 2004;35:193–200.

    Article  Google Scholar 

  19. Association WM. World Medical Association Declaration of Helsinki Ethical Principles for Medical Research Involving Human Subjects. JAMA. 2013;310:2191–4.

    Article  Google Scholar 

  20. Philpott MP, Green MR, Kealey T. Human hair growth in vitro. J Cell Sci. 1990;97(Pt 3):463–71.

    Article  CAS  Google Scholar 

  21. Ito T, et al. Interferon-gamma is a potent inducer of catagen-like changes in cultured human anagen hair follicles. Br J Dermatol. 2005;152:623–31.

    Article  CAS  Google Scholar 

  22. Schneider MR, Schmidt-Ullrich R, Paus R. The hair follicle as a dynamic miniorgan. Curr Biol. 2009;19:R132-142.

    Article  CAS  Google Scholar 

  23. Kloepper JE, et al. Methods in hair research: how to objectively distinguish between anagen and catagen in human hair follicle organ culture. Exp Dermatol. 2010;19:305–12.

    Article  CAS  Google Scholar 

  24. Peters E, et al. Control of human hair growth by neurotrophins: brain-derived neurotrophic factor inhibits hair shaft elongation, induces catagen, and stimulates follicular transforming growth factor beta2 expression. J Invest Dermatol. 2005;124:675–85.

    Article  CAS  Google Scholar 

  25. Dodt HU, et al. Ultramicroscopy: three-dimensional visualization of neuronal networks in the whole mouse brain. Nat Methods. 2007;4:331–6.

    Article  CAS  Google Scholar 

  26. Adema GJ, Bakker AB, de Boer AJ, Hohenstein P, Figdor CG. pMel17 is recognised by monoclonal antibodies NKI-beteb, HMB-45 and HMB-50 and by anti-melanoma CTL. Br J Cancer. 1996;73:1044–8.

    Article  CAS  Google Scholar 

  27. O’Sullivan JDB, et al. The biology of human hair greying. Biol Rev Camb Philos Soc. 2021;96:107–28.

    Article  CAS  Google Scholar 

  28. Commo S, Bernard BA. Melanocyte subpopulation turnover during the human hair cycle: an immunohistochemical study. Pigment Cell Res. 2000;13:253–9.

    Article  CAS  Google Scholar 

  29. Tobin DJ, Paus R. Graying: gerontobiology of the hair follicle pigmentary unit. Exp Gerontol. 2001;36:29–54.

    Article  CAS  Google Scholar 

  30. Hoashi T, et al. Glycoprotein nonmetastatic melanoma protein b, a melanocytic cell marker, is a melanosome-specific and proteolytically released protein. FASEB J. 2010;24:1616–29.

    Article  CAS  Google Scholar 

  31. Horikawa T, et al. DOPA-negative melanocytes in the outer root sheath of human hair follicles express premelanosomal antigens but not a melanosomal antigen or the melanosome-associated glycoproteins tyrosinase, TRP-1, and TRP-2. J Invest Dermatol. 1996;106:28–35.

    Article  CAS  Google Scholar 

  32. Slominski A, et al. Hair follicle pigmentation. J Invest Dermatol. 2005;124:13–21.

    Article  CAS  Google Scholar 

  33. Lee JH, Fisher DE. Melanocyte stem cells as potential therapeutics in skin disorders. Expert Opin Biol Ther. 2014;14:1569–79.

    Article  CAS  Google Scholar 

  34. Shi Y, et al. Premature graying as a consequence of compromised antioxidant activity in hair bulb melanocytes and their precursors. PLoS ONE. 2014;9: e93589.

    Article  Google Scholar 

  35. Ressler S, et al. p16INK4A is a robust in vivo biomarker of cellular aging in human skin. Aging Cell. 2006;5:379–89.

    Article  CAS  Google Scholar 

  36. Niedernhofer LJ, et al. Nuclear Genomic Instability and Aging. Annu Rev Biochem. 2018;87:295–322.

    Article  CAS  Google Scholar 

  37. Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. 2013;153:1194–217.

    Article  CAS  Google Scholar 

  38. Kudlova N, et al. An efficient, non-invasive approach for in-vivo sampling of hair follicles: design and applications in monitoring DNA damage and aging. Aging (Albany NY). 2021;13:25004–24.

    Article  CAS  Google Scholar 

  39. Matsumura H, et al. Hair follicle aging is driven by transepidermal elimination of stem cells via COL17A1 proteolysis. Science. 2016;351:aad4395.

    Article  Google Scholar 

  40. Lu Z, et al. Profiling the response of human hair follicles to ultraviolet radiation. J Invest Dermatol. 2009;129:1790–804.

    Article  CAS  Google Scholar 

  41. Harris ML, et al. A dual role for SOX10 in the maintenance of the postnatal melanocyte lineage and the differentiation of melanocyte stem cell progenitors. PLoS Genet. 2013;9: e1003644.

    Article  CAS  Google Scholar 

  42. Harris ML, et al. A direct link between MITF, innate immunity, and hair graying. PLoS Biol. 2018;16: e2003648.

    Article  Google Scholar 

  43. Stone RC, Aviv A, Paus R. Telomere Dynamics and Telomerase in the Biology of Hair Follicles and their Stem Cells as a Model for Aging Research. J Invest Dermatol. 2021;141:1031–40.

    Article  CAS  Google Scholar 

  44. Kaur K, Kaur R, Bala I. Therapeutics of premature hair graying: A long journey ahead. J Cosmet Dermatol. 2019. https://doi.org/10.1111/jocd.13000.

    Article  Google Scholar 

  45. Jo SK, et al. Three Streams for the Mechanism of Hair Graying. Ann Dermatol. 2018;30:397–401.

    Article  CAS  Google Scholar 

  46. Kurita K, et al. Suppression of progressive loss of coat color in microphthalmia-vitiligo mutant mice. J Invest Dermatol. 2005;125:538–44.

    Article  CAS  Google Scholar 

  47. Chang S, et al. Essential role of limiting telomeres in the pathogenesis of Werner syndrome. Nat Genet. 2004;36:877–82.

    Article  CAS  Google Scholar 

  48. Stout R, Birch-Machin M. Mitochondria's Role in Skin Ageing. Biology (Basel). 2019;8

  49. Kauser S, Westgate GE, Green MR, Tobin DJ. Human hair follicle and epidermal melanocytes exhibit striking differences in their aging profile which involves catalase. J Invest Dermatol. 2011;131:979–82.

    Article  CAS  Google Scholar 

  50. Wood JM, et al. Senile hair graying: H2O2-mediated oxidative stress affects human hair color by blunting methionine sulfoxide repair. FASEB J. 2009;23:2065–75.

    Article  CAS  Google Scholar 

  51. Pruche F, Kermici M, Prunieras M. Changes in glutathione content in human hair follicle keratinocytes as a function of age of donor: relation with glutathione dependent enzymes. Int J Cosmet Sci. 1991;13:117–24.

    Article  CAS  Google Scholar 

  52. Di Micco R, Krizhanovsky V, Baker D, d’Adda di Fagagna F. Cellular senescence in ageing: from mechanisms to therapeutic opportunities. Nat Rev Mol Cell Biol. 2021;22:75–95.

    Article  Google Scholar 

  53. Taylor CT, Colgan SP. Regulation of immunity and inflammation by hypoxia in immunological niches. Nat Rev Immunol. 2017;17:774–85.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We greatly appreciate the valuable technical support from Yan-wei Xu PhD, Xiao-xiong Zhou PhD, Jia-rui Zhang PhD and Yu-yang Gan PhD. We also would like to thank Editage (www.editage.cn) for English language editing.

Funding

This study was supported by the National Natural Science Foundation of China (Grant 81701929, No.81971889, No.81902013, No.82103763), the Natural Science Foundation of Guangdong Province (Grant No.2019A1515012170, Grant No.2020A1515110700). We also like to acknowledge all the patients and volunteers who have kindly contributed samples.

Author information

Authors and Affiliations

  1. Department of Plastic and Aesthetic Surgery, Nan Fang Hospital, Southern Medical University, 1838 North, Guangzhou, 510515, China

    Da-mao Dai, Ye He, Qing Guan, Zhe-xiang Fan, Yunmin Zhu, Jin Wang, Shulian Wu, Jian Chen, Demengjie Le, Zhi-qi Hu, Qian Qu & Yong Miao

Authors
  1. Da-mao Dai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ye He
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Qing Guan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zhe-xiang Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yunmin Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jin Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shulian Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jian Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Demengjie Le
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Zhi-qi Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Qian Qu
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Yong Miao
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All the authors agree with the contents of the manuscript and to have it published. Da-mao Dai: conceptualization, methodology, writing—review and editing, resources, formal analysis, project administration, investigation. Ye He & Qing Guan: Conceptualization, methodology, formal analysis, data curation, writing–original draft, visualization, investigation. Zhe-xiang Fan & Yun-min Zhu: Data Curation, Formal analysis, Resources, Investigation, Writing—Original Draft. Jin Wang: Conceptualization, validation, and investigation. Shu-lian Wu & Jian Chen: Data curation and formal analysis. De-meng-jie Le: Methodology and visualization. Zhi-qi Hu: Funding acquisition, supervision, writing, review, and editing. Qian Qu & Yong Miao: Funding acquisition, supervision, project administration, writing, review, and editing.

Corresponding authors

Correspondence to Zhi-qi Hu, Qian Qu or Yong Miao.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOC 1966 KB)

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dai, Dm., He, Y., Guan, Q. et al. Modeling human gray hair by irradiation as a valuable tool to study aspects of tissue aging. GeroScience 45, 1215–1230 (2023). https://doi.org/10.1007/s11357-022-00592-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11357-022-00592-6

Keywords

Search

Navigation