Clonal Hematopoiesis and Aging in a Naturalistic Population of Rhesus Macaques

Understanding why individuals vary in the onset and progression of aging-related diseases is important for developing interventions to extend healthy human lifespans. A possible mechanism underlying variation in aging and disease is increased somatic mutations with age. One result of somatic mutation, clonal hematopoiesis (CH), is the overrepresentation of blood cells originating from a single progenitor stem cell. When these clones become more frequent (≥4% of white blood cells), it is called “clonal hematopoiesis of indeterminate potential” (CHIP), which is associated with aging, pre-cancer, inflammation, and cardiovascular disease. Frequency of these mutations may also be predicted by facets of individuals’ environments, such as experiencing significant adverse life events, which have been linked to acceleration of other aspects of aging. We hypothesize that older individuals, particularly those that have experienced environmental adversity, will be more likely to have CH mutations. We also expect to see expansion of CHIP clones over time within individuals. We are testing these hypotheses in a population of free-ranging rhesus macaques, which have similar immune systems to humans and experience various types of environmental adversity. We have sequenced DNA from this population and are working to identify animals with CHIP. We plan to test whether demographic and environmental factors (i.e., adversity, sex) influence the development of CH driver mutations during aging, along with analyzing clonal dynamics and phenotypic effects in individuals with CHIP. Our findings will provide insight into the factors that influence CHIP development and progression, ultimately contributing to interventions to delay or prevent CHIP.