Ageing of the Haematopoietic Stem Cell Compartment and Clonal Selection

Abstract

Background: Ageing of the haematopoietic stem cell compartment is described as declining cell function, largely in mice, and as
clonal selection measured in human blood.
Objective: To separate the evidence by species and by driver gene, and to ask what each body of work supports clinically.
Methods: Narrative review of population cohorts, clonal phylogenies, transplantation series and mouse experiments.
Findings: In 17,182 persons, clonal haematopoiesis rose from 5.6% at 60-69 years to 18.4% at 90 years and above. Growth rates
differed by driver, from about 5% per year for DNMT3A to over 50% for SRSF2 P95H among 385 individuals. In 10 subjects, 30-60%
of haematopoiesis over 75 years derived from 12-18 clones, a collapse that aged mice did not display.
Conclusions: The evidence supports driver-specific rather than pooled risk statements and labelling rejuvenation results as
mouse work; it does not show that oligoclonal haematopoiesis is typical after 70.