Aging leads to well characterised changes in both innate and adaptive immunity resulting in reduced immune function and an increased frequency of infections among older individuals. These changes include reduced haematopoietic stem cell potential, reduced lymphocyte output and function, and an increased frequency of “virtual” memory CD8⁺ T cells, that is, cells that express memory-like markers without ever encountering their cognate antigen. Together these changes limit the ability of CD8⁺ T cell responses to be generated toward new infections. 

Although much is known about the consequences of aging on immune cell development and function, the molecular events underlying this process remain unclear. Here we identify that the immunological changes associated with ageing are recapitulated in mice deficient in the histone methyltransferases Suv39h1 and h2 (Suv39dn). Since loss of both Suv39h genes has previously been shown to result in severe defects during embryogenesis, we reconstituted the immune system of irradiated recipient CD45^Ly5.1 mice with e13 fetal livers from either WT or Suv39dn embryos (CD45^Ly5.2). Reduced haematopoietic stem cell potential was revealed through poor reconstitution by the Suv39dn cells compared with WT cells. Furthermore, decreased CD8⁺ T cell numbers and an increased frequency of memory CD8⁺ T cells were observed in the lymph nodes and spleens of Suv39dn chimeras compared with WT chimeras. Importantly, these changes are not observed in single Suv39h1 or h2 null mice.

Suv39h1 expression is known to decrease with age, and Suv39h2, whilst ubiquitously expressed during embryogenesis, is expressed at low levels in all adult tissues except the testes. Taken together, our results therefore suggest that the decreased levels of Suv39h1 and h2 in aging may drive the loss of immune function and susceptibility of older individuals to infections.