A new study provides some of the first links between relatively common mutations in the blood cells of elderly humans and atherosclerosis. Though cardiovascular disease, which is characterized in part by atherosclerosis, or plaque build-up, is a leading cause of death in the elderly, almost 60% of elderly patients with atherosclerotic cardiovascular disease (CVD) exhibit no conventional risk factors, or just one. This and other data suggest that age-dependent risk factors that haven't yet been identified may contribute to CVD. Scientists know that accumulation of somatic DNA mutations is a feature of aging, though little data exists on the role of such mutations in age-associated disorders beyond cancer. Meanwhile, recent human studies indicate that aging is associated with an increase in somatic mutations in the hematopoietic system, which gives rise to blood cells; these mutations provide a competitive growth advantage to the mutant hematopoietic cells, allowing for their clonal expansion - a process that has been shown to be associated with a greater incidence of atherosclerosis, though specifically how remains unclear. In this study, Jose Fuster and colleagues investigated whether there is a direct relationship between such mutations and atherosclerosis. They generated a mouse model to investigate how one of the genes commonly mutated in blood cells of elderly humans, TET2, affects plaque development. Plaque formation accelerated in mice transplanted with Tet2-deficient bone marrow cells, they report, likely through increasing macrophage-driven inflammation in the artery wall. The results strengthen support for the hypothesis that hematopoietic mutations play a causal role in atherosclerosis.