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Stem cell competition orchestrates skin homeostasis and ageing.


Maximus Peto’s Commentary

I almost passed on this paper, but then I got to the part where they said “forced maintenance of COL17A1 rescues skin organ ageing” and it made me wonder how exactly they defined “skin aging”. Some readers on this distribution list may want to look into this in more detail.


Stem cell competition orchestrates skin homeostasis and ageing.
Nature. 2019 Apr;568(7752):344-350.
Liu N, Matsumura H, Kato T, Ichinose S, Takada A, Namiki T, Asakawa K, Morinaga H, Mohri Y, De Arcangelis A, Geroges-Labouesse E, Nanba D, Nishimura EK
DOI: 10.1038/s41586-019-1085-7
PubMed publication date (edat): 4/5/2019

Abstract

Stem cells underlie tissue homeostasis, but their dynamics during ageing-and the relevance of these dynamics to organ ageing-remain unknown. Here we report that the expression of the hemidesmosome component collagen XVII (COL17A1) by epidermal stem cells fluctuates physiologically through genomic/oxidative stress-induced proteolysis, and that the resulting differential expression of COL17A1 in individual stem cells generates a driving force for cell competition. In vivo clonal analysis in mice and in vitro 3D modelling show that clones that express high levels of COL17A1, which divide symmetrically, outcompete and eliminate adjacent stressed clones that express low levels of COL17A1, which divide asymmetrically. Stem cells with higher potential or quality are thus selected for homeostasis, but their eventual loss of COL17A1 limits their competition, thereby causing ageing. The resultant hemidesmosome fragility and stem cell delamination deplete adjacent melanocytes and fibroblasts to promote skin ageing. Conversely, the forced maintenance of COL17A1 rescues skin organ ageing, thereby indicating potential angles for anti-ageing therapeutic intervention.
Comment in
* Elimination of unfit cells in young and ageing skin. [Nature. 2019] * Putting Cell Competition under the Microscope. [Dev Cell. 2019]

PMID: 30944469
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Maximus Peto

Max Peto is a longevity researcher and founder of Long Life Labs. A biochemist by training, he studies the biochemistry of aging and longevity and has worked with research organizations such as SENS Research Foundation, Methuselah Foundation, BioAge Labs, Life Extension Foundation, and Ichor Therapeutics. His work at Long Life Labs is focused on empowering people to understand and manage the most critical factors for better health and longer life.

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