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Senescent human melanocytes drive skin ageing via paracrine telomere dysfunction
Author(s) -
Victorelli Stella,
Lagnado Anthony,
Halim Jessica,
Moore Will,
Talbot Duncan,
Barrett Karen,
Chapman James,
Birch Jodie,
Ogrodnik Mikolaj,
Meves Alexander,
Pawlikowski Jeff S,
Jurk Diana,
Adams Peter D,
Heemst Diana,
Beekman Marian,
Slagboom P Eline,
Gunn David A,
Passos João F
Publication year - 2019
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2019101982
Subject(s) - biology , telomere , ageing , paracrine signalling , melanocyte , cellular aging , skin aging , microbiology and biotechnology , genetics , dna , dermatology , melanoma , receptor , medicine
Cellular 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 p16 INK4A during human skin ageing. Aged melanocytes also display additional markers of senescence such as reduced HMGB 1 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 CXCR 3‐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 ABT 737 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.