Clonal Hematopoiesis in Aging

Clonal hematopoiesis of indeterminate potential (CHIP) is a common, age-associated condition characterized by the acquisition of somatic mutations. This concise review explores our current understanding of the mechanisms that influence the development of clonality with aging and its potential malignant and non-malignant clinical implications.

Aging of the hematopoietic system results in phenotypic changes that favor clonal dominance. Cell-extrinsic factors provide additional selective pressures that further shape clonal architecture. Even so, small clones with candidate driver mutations appear to be ubiquitous with age and largely benign in the absence of strong selective pressures. Benign clonal expansion may compensate for the loss of regenerative HSC capacity as we age.

CHIP is a marker of aging that reflects the biologic interplay between HSC aging and cell-extrinsic factors. The clinical significance of CHIP is highly variable and dependent on clinical context. Distinguishing the causal relationships and confounding factors that regulate clonal behavior will be essential to define the mechanistic role of CHIP in aging and potentially mitigate its clinical consequences.