Growing old in the age of heterogeneity: the perils of shifting clonality

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.

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.

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.