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Lookup NU author(s): Stella Victorelli, Dr Anthony Lagnado, Jessica Halim, Dr James ChapmanORCiD, Dr Jodie Birch, Dr Mikolaj Ogrodnik, Dr Diana JurkORCiD, Dr Joao Passos
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© 2019 The AuthorsCellular senescence has been shown to contribute to skin ageing. However, the role of melanocytes in the process is understudied. Our data show that melanocytes are the only epidermal cell type to express the senescence marker p16INK4A during human skin ageing. Aged melanocytes also display additional markers of senescence such as reduced HMGB1 and dysfunctional telomeres, without detectable telomere shortening. Additionally, senescent melanocyte SASP induces telomere dysfunction in paracrine manner and limits proliferation of surrounding cells via activation of CXCR3-dependent mitochondrial ROS. Finally, senescent melanocytes impair basal keratinocyte proliferation and contribute to epidermal atrophy in vitro using 3D human epidermal equivalents. Crucially, clearance of senescent melanocytes using the senolytic drug ABT737 or treatment with mitochondria-targeted antioxidant MitoQ suppressed this effect. In conclusion, our study provides proof-of-concept evidence that senescent melanocytes affect keratinocyte function and act as drivers of human skin ageing.
Author(s): Victorelli S, Lagnado A, Halim J, Moore W, Talbot D, Barrett K, Chapman J, Birch J, Ogrodnik M, Meves A, Pawlikowski JS, Jurk D, Adams PD, van Heemst D, Beekman M, Slagboom PE, Gunn DA, Passos JF
Publication type: Article
Publication status: Published
Journal: EMBO Journal
Year: 2019
Volume: 38
Issue: 23
Print publication date: 02/12/2019
Online publication date: 21/10/2019
Acceptance date: 18/09/2019
ISSN (print): 0261-4189
ISSN (electronic): 1460-2075
Publisher: Wiley-Blackwell Publishing Ltd.
URL: https://doi.org/10.15252/embj.2019101982
DOI: 10.15252/embj.2019101982
PubMed id: 31633821
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