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.

J.D. is supported by an EMBO long-term fellowship, and M.A.S. is funded by a La Caixa bank studentship. This work was funded in part by a Plan Nacional grant to W.M.K. from the Spanish/nMinistry for Science and Innovation (SAF2010-18829)