There is some debate over whether accumulated stochastic nuclear DNA damage is significant in aging over the present human life span in ways other than increased cancer risk, and a lack of good studies that provide evidence to support theoretical arguments in either direction. Stochastic DNA damage is observed, different in every cell, but like many of the changes of aging this cannot yet be effectively repaired, and thus it is very challenging to distinguish its effects in isolation. On the side of arguing for significance, the mechanism by which it contributes to aging is assumed to be a growing level of general dysfunction in cellular populations. This conjecture is supported by work such as that shown here, in which specific mutations are pointed out as problematic for the normal function of tissues, but the challenge here is still that there is no good demonstration of its significance in normal aging over and above other mechanisms, such as those outlined in the SENS vision of aging. It might only be a problem if ten times as many cells are mutated than normally happens. Or a hundred times. One possible next step would be gene therapy to repair mutated instances of the gene where they occur in order to assess the size of the effect, but that sort of study hasn't taken place yet.
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 percent 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, researchers investigated whether there is a direct relationship between such mutations and atherosclerosis. They generated an experimental model to investigate how one of the genes commonly mutated in blood cells of elderly humans, TET2, affects plaque development. Plaque formation accelerated in the models transplanted with Tet2-deficient bone marrow cells, 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. "Our studies show that mutations in our white blood cells, that we acquire as we age, may cause cardiovascular disease. Understanding this new mechanism of cardiovascular disease could lead to the development of new therapies to treat individuals who suffer from heart and blood vessel ailments due to these mutations. Furthermore, because these mutations become prevalent starting at middle age, these studies suggest that genetic analyses of blood samples could add to the predictive value of traditional risk factors - high cholesterol, hypertension, diabetes, and smoking - that are currently monitored."