title: Hair follicle aging is driven by transepidermal elimination of stem cells via COL17A1 proteolysis.
abstract: Hair thinning and loss are prominent aging phenotypes but have an unknown mechanism. We show that hair follicle stem cell (HFSC) aging causes the stepwise miniaturization of hair follicles and eventual hair loss in wild-type mice and in humans. In vivo fate analysis of HFSCs revealed that the DNA damage response in HFSCs causes proteolysis of type XVII collagen (COL17A1/BP180), a critical molecule for HFSC maintenance, to trigger HFSC aging, characterized by the loss of stemness signatures and by epidermal commitment. Aged HFSCs are cyclically eliminated from the skin through terminal epidermal differentiation, thereby causing hair follicle miniaturization. The aging process can be recapitulated by Col17a1 deficiency and prevented by the forced maintenance of COL17A1 in HFSCs, demonstrating that COL17A1 in HFSCs orchestrates the stem cell-centric aging program of the epithelial mini-organ.
authors.affiliation: Department of Stem Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Matsumura
authors.affiliation: Department of Stem Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Mohri
authors.affiliation: Department of Stem Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan. Department of Stem Cell Medicine, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa 920-0934, Japan.
authors.forename: Nguyen Thanh
authors.initials: NT
authors.lastname: Binh
authors.affiliation: Department of Stem Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Morinaga
authors.affiliation: Department of Stem Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Fukuda
authors.affiliation: Departments of Dermatology and Cell Biology, New York University School of Medicine, New York, NY, USA.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Ito
authors.affiliation: Beppu Garden-Hill Clinic, Kurata Clinic, Beppu city, Oita 8740831, Japan.
authors.forename: Sotaro
authors.initials: S
authors.lastname: Kurata
authors.affiliation: Department of Genetics, Cancer Genomics Center, Erasmus MC, Room Ee 722, Dr. Wytemaweg 80, 3015 CN Rotterdam, Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Hoeijmakers
authors.affiliation: Department of Stem Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan. nishscm@tmd.ac.jp.
authors.forename: Emi K
authors.initials: EK
authors.lastname: Nishimura
mesh_terms: D000368:Aged; D000375:Aging / Q000378:metabolism / Q000473:pathology; D000505:Alopecia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001324:Autoantigens / Q000235:genetics; D002454:Cell Differentiation; D016922:Cellular Senescence / Q000235:genetics / Q000502:physiology*; D004249:DNA Damage; D003896:Desmosomes / Q000378:metabolism / Q000473:pathology; D005260:Female; D042822:Genomic Instability; D018859:Hair Follicle / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D024041:Non-Fibrillar Collagens / Q000172:deficiency* / Q000235:genetics; D059748:Proteolysis; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology*; D000097805:Collagen Type XVII
chemical_list: D001324:Autoantigens; D024041:Non-Fibrillar Collagens; D000097805:Collagen Type XVII