Ho, Ya-HsuanToro, Raquel delRivera Torres, JoséRak, JustynaKorn, ClaudiaGarcía García, AndrésMacías, DavidGonzález Gómez, CristinaMonte, Alberto delMéndez Ferrer, SimónEt al.2022-02-242022-02-242019Ho, Y.-H., Toro, R., Rivera-Torres, J., Rak, J., Korn, C., García-García, A., Macías, D., González-Gómez, C., del Monte, A., Wittner, M., Waller, A. K., Foster, H. R., López-Otín, C., Johnson, R. S., Nerlov, C., Ghevaert, C., Vainchenker, W., Louache, F., Andrés, V., & Méndez-Ferrer, S. (2019). Remodeling of bone marrow hematopoietic stem cell niches promotes myeloid cell expansion during premature or physiological aging. Cell Stem Cell, 25(3), 407-418.e6. https://doi.org/10.1016/j.stem.2019.06.0071934-59091875-9777http://hdl.handle.net/11268/10828Hematopoietic stem cells (HSCs) residing in the bone marrow (BM) accumulate during aging but are functionally impaired. However, the role of HSC-intrinsic and -extrinsic aging mechanisms remains debated. Megakaryocytes promote quiescence of neighboring HSCs. Nonetheless, whether megakaryocyte-HSC interactions change during pathological/natural aging is unclear. Premature aging in Hutchinson-Gilford progeria syndrome recapitulates physiological aging features, but whether these arise from altered stem or niche cells is unknown. Here, we show that the BM microenvironment promotes myelopoiesis in premature/physiological aging. During physiological aging, HSC-supporting niches decrease near bone but expand further from bone. Increased BM noradrenergic innervation promotes β2-adrenergic-receptor(AR)-interleukin-6-dependent megakaryopoiesis. Reduced β3-AR-Nos1 activity correlates with decreased endosteal niches and megakaryocyte apposition to sinusoids. However, chronic treatment of progeroid mice with β3-AR agonist decreases premature myeloid and HSC expansion and restores the proximal association of HSCs to megakaryocytes. Therefore, normal/premature aging of BM niches promotes myeloid expansion and can be improved by targeting the microenvironment.engAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/Movilización de célula madre hematopoyéticaNicho de células madrejournal article10.1016/j.stem.2019.06.007open accessBiología celularEnvejecimientoEfectos fisiológicos