Ageing Through the Looking-Glass: The Different Flavours of Clonal Haematopoiesis

Clonal haematopoiesis (CH) is the presence of acquired mutations in blood cells and is a consequence of ageing that is linked to malignancy, cardiovascular disease and other diseases of ageing. CH is a reflection of genomic instability with ageing; however, there is evidence that CH may exacerbate features of normal ageing, including inflammageing and immunosenescence, and more directly contribute to disease causation. CH can manifest as mosaic loss of X or Y, autosomal mosaic chromosomal rearrangements, or point mutations or small insertions or deletions. Until recently, little has been known about the relationship between different forms of CH and other biomarkers of ageing, including whether they are more likely to co-exist, whether they work synergistically to promote clonal expansion, and whether they have independent impacts on risk of clinical outcomes. Defining the overlap between different forms of CH and other markers of ageing is important to understand the biological processes involved in ageing, and the mechanisms underlying the associations with diseases of ageing. Here we provide an overview of the current literature on intersections of different forms of CH, the clinical implications of these, and a perspective on how CH enhances our understanding of the biology of ageing.