title: Age-associated inflammation inhibits epidermal stem cell function.
abstract: Altered stem cell homeostasis is linked to organismal aging. However, the mechanisms involved remain poorly understood. Here we report novel alterations in hair follicle stem cells during skin aging, including increased numbers, decreased function, and an inability to tolerate stress. Performing high-throughput RNA sequencing on aging stem cells, cytokine arrays, and functional assays, we identify an age-associated imbalance in epidermal Jak-Stat signaling that inhibits stem cell function. Collectively, this study reveals a role for the aging epidermis in the disruption of cytokine and stem cell homeostasis, suggesting that stem cell decline during aging may be part of broader tumor-suppressive mechanisms.
authors.affiliation: Centre for Genomic Regulation, Barcelona 08003, Spain.
authors.forename: Jason
authors.initials: J
authors.lastname: Doles
authors.forename: Mekayla
authors.initials: M
authors.lastname: Storer
authors.forename: Luca
authors.initials: L
authors.lastname: Cozzuto
authors.forename: Guglielmo
authors.initials: G
authors.lastname: Roma
authors.forename: William M
authors.initials: WM
authors.lastname: Keyes
mesh_terms: D000375:Aging; D000818:Animals; D002452:Cell Count; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D000078404:Epidermal Cells; D004817:Epidermis / Q000201:enzymology; D018859:Hair Follicle / Q000166:cytology / Q000201:enzymology; D006706:Homeostasis / Q000502:physiology; D007249:Inflammation; D053612:Janus Kinases / Q000037:antagonists & inhibitors; D051379:Mice; D008810:Mice, Inbred C57BL; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology* / Q000201:enzymology
chemical_list: D016207:Cytokines; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D053612:Janus Kinases