Emerging role of the centromere in human lymphocyte proliferation and aging – LymphoCentro

T cells are essential for immune responses, but they become dysfunctional and less proliferative during aging. Aging is characterized by increased aneuploidy. The hallmark is the exponential loss of Y chromosome (LOY) in leukocytes during male aging, which is associated with increased disease risk and mortality. Centromeres ensure chromosome segregation during mitosis and prevent aneuploidy and senescence. The role of centromeres in immune aging and LOY is unknown. We recently discovered a significant population of human CD4+ T cells with reduced levels of an essential centromeric protein. These results raise a novel question : what is the role of centromere regulation in T cell biology ? Here, we propose to characterize centromere regulation in T cells, to assess its role in LOY and T cell functions, and to determine its relevance during aging.