Growing old in the age of heterogeneity the perils of shifting clonalityGustafsson, Karina,b,c; Scadden, David T.a,b,cCurrent Opinion in Hematology: July 2019 - Volume 26 - Issue 4 - p 222–227 doi: 10.1097/MOH.0000000000000513 HEMATOPOIESIS: Edited by Hal E. Broxmeyer and Maegan L. Capitano Buy Abstract Author InformationAuthors Article MetricsMetrics Purpose of review Hematopoietic stem cells (HSC) are functionally heterogeneous in a clone-specific manner. The complexity of that heterogeneous mix of cells is progressively lost with age as a myeloid-dominant hematopoietic system is established. Yet, the function of this diversity, as well as the consequences of its loss, remains unknown. This review will bring together recent advances in HSC diversity and novel insights into myeloid heterogeneity and specification in order to bring focus on how this may affect the ageing individual. Recent findings The ageing haematopoietic system is dominated by a low number of active HSC clones that produce an excess of myeloid cells. In addition, individual myeloid progenitors and their mature progeny are proving to be more functionally restricted than previously recognized. The presence or absence of a particular type of myeloid cell can greatly affect the outcome of various pathological processes. Summary Myeloid cells are important drivers of many ageing-associated diseases. The loss of HSC heterogeneity, with a possible concomitant restriction of myeloid cell diversity, could significantly impact health during ageing. aHarvard Stem Cell Institute, Cambridge bMGH Center for Regenerative Medicine and Cancer Center, Boston cDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts, USA Correspondence to David T. Scadden, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA. Tel: +1 617 726 5615; e-mail: email@example.com Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.