Wnt/β-catenin signaling promotes aging-associated hair graying in mice

Abstract

Canities is an obvious sign of aging in mouse and human, shown as hair graying. Melanocytes in the hair follicle show cyclic activity with hair cycling, which transitions from anagen, catagen to telogen. How the hairs turn gray during aging is not completely uncovered. Here, by using immunostaining and LacZ staining in Dct-LacZ mice, we show that β-catenin is expressed in melanocytes during hair cycling. RT-PCR, western blot and immunostaining show that β-catenin expression is significantly increased in both anagen and telogen skin of aged mice, when compared to the anagen and telogen skin of young mice, respectively. Overexpression of Wnt10b not only accelerates hair follicle to enter anagen phase, but also promotes melanocytes differentiation in young adult mice (2-month old), with increased β-catenin expression in melanocytes at the secondary hair germ and matrix region of regenerated hair follicles. Overexpression of Wnt10b also promotes melanocyte progenitor cells differentiation in vitro. Our data suggest that increased Wnt signaling promotes excessive differentiation of melanocytes, leading to exhaustion of melanocyte stem cells and eventually canities in aged mice.

Genome‐wide scan reveals divergent selection among taurine and zebu cattle populations from different regions

“…) and is implicated in promoting melanocyte differentiation (Zhang et al . ). The Hippo pathway plays several prominent functions including regulation of homeostasis under oxidative stress and DNA damage response (Mao et al .…”

“…), and in promoting melanocyte differentiation (Zhang et al . ). Again, removal of this gene has led to diminished size of the appendicular skeleton in mice (Bandyopadhyay et al .…”

WNT Signaling in Disease

“…One mouse study found that β-catenin expression is significantly elevated in the skin of aged mice through WNT10b/β-catenin signaling promoting melanocyte stem cell differentiation. The authors concluded that the increase in WNT signaling is insufficient to induce hair regeneration but may promote melanocyte stem cell differentiation resulting in a decreased number of melanocyte stem cells and eventually hair graying [55].…”

Regulation of melanocyte stem cells in the pigmentation of skin and its appendages: Biological patterning and therapeutic potentials

“…Loss of the key signalling molecules (eg, Bcl2) that maintain the survival of McSCs causes the deletion of McSCs and hair greying . Forced activation or increased expression of Wnt signalling in McSCs induces exhaustion of McSCs and premature hair greying; TGF‐β type 2 receptor deficiency in hair follicle bulge causes incomplete maintenance of McSC quiescence, leading to mild hair greying in mice …”