Competition between stem cells, driven by a specific collagen protein (COL17A1), is critical to maintain ‘youthful’ skin in mice, but with time also causes the skin to age, reports a paper published online in Nature this week. The work also identifies compounds that could potentially represent a new anti-ageing intervention.
Aged skin is characterized by thinning, fragility and delayed wound healing, as well as reduced reservoirs of skin cells such as keratinocytes and melanocytes. The phenomenon of stem cell competition, in which the clonal offspring of certain stem cells out-grow other clones, has been implicated in maintaining tissue fitness.
Emi Nishimura and colleagues investigated the role of stem cell competition in skin ageing in the tails of mice, where the skin shares many features with human skin and ages in a similar manner. The authors show that stem cell competition is driven by the collagen protein COL17A1, the expression of which decreases with age. They observe that expression of COL17A1 varies between stem cells, and that those with higher levels remain firmly anchored to, and divide symmetrically along, the basement membrane, and push out nearby cells that express less COL17A1. The competition between cells helps to maintain the overall structure and integrity of the skin. However, the expression of COL17A1 declines with age and in response to stresses, such as oxidation or exposure to UV radiation. As COL17A1 levels ultimately decline in all stem cells, the skin ages.
The authors also identified two chemical compounds that maintained COL17A1 expression in human keratinocytes - Y27632 and apocynin. These drugs also promoted wound healing in mice. Together, these results uncover the importance of stem cell competition and COL17A1 in skin homeostasis and ageing, and represent an important step towards skin regeneration and anti-ageing medicine.