Figure 1 |. CHIP as a mechanistic link of comorbidities.

Clonal hematopoiesis of intermediate potential (CHIP) is an aging-related phenomenon in which hematopoietic stem and progenitor cells (HSPCs) acquire somatic mutations resulting in a proliferative advantage (vs. normal HSPCs) and selective expansion of a genetically distinct subset of mutant leukocyte progeny, which thus comprise an outsized fraction of total leukocytes in the periphery^3–6. CHIP-mutant leukocytes exhibit altered phenotypes that not only contribute to systemic inflammation but also promote the pathogenesis of chronic diseases, including cardiovascular disease (CVD), the disorder most strongly linked with CHIP^{9,12,19,52–54,128,130}. CHIP-driven chronic disorders depicted here often coexist as comorbidities; it is thus possible that CHIP acts as a common mechanistic basis that contributes to their emergence in the same patients¹⁹. CKD, chronic kidney disease; COPD, chronic obstructive pulmonary disease; MASLD, metabolic dysfunction-associated steatotic liver disease.