There is plenty of evidence to suggest that the persistent herpesvirus species cytomegalovirus (CMV) plays an important role in immune system aging. A majority of people carry the virus by the time they reach old age, and its presence causes an ever-increasing number of immune cells to become uselessly specialized to deal with CMV rather than able to respond to new threats. There are other contributing causes to immune system aging, but this seems like a potentially important one, for all that there is still work to be done to definitively prove the case. It is worth chasing this to a conclusion, because a state of too many CMV-specialized immune cells is reversible by the targeted removal of these cells, which will trigger their replacement with new non-specialized cells. This sort of approach has been demonstrated in laboratory animals for similar situations, and so is a possible tool for the rejuvenation toolkit.
As is the case for many potential causes of aging, it would be faster and cheaper to carry out destruction of CMV-specialized cells and then see what happens rather than to fully investigate all of the mechanisms and come to a conclusion without the data from such a prospective treatment. Nonetheless, the research community tends to take the latter rather than the former path. This open access review paper looks over what is known and still unknown about CMV in the context of immune system aging:
Immunosenescence, defined as the age-associated dysregulation and dysfunction of the immune system, is characterized by impaired protective immunity and decreased efficacy of vaccines. An increasing number of immunological, clinical and epidemiological studies suggest that persistent Cytomegalovirus (CMV) infection is associated with accelerated aging of the immune system and with several age-related diseases. However, current evidence on whether and how human CMV (HCMV) infection is implicated in immunosenescence and in age-related diseases remains incomplete and many aspects of CMV involvement in immune aging remain controversial.
After primary infection, CMV is carried for the lifetime of its host. Viral persistence is based on complex interactions between multiple viral and host determinants. These interactions generally result in a carefully negotiated and clinically "innocuous" balance between the virus and the immunocompetent host. Indeed, CMV rarely produces symptoms in the host unless the balance is upset by reduced immune competency of the host.
The co-existence of human CMV in healthy, and even more so, in elderly individuals is still a poorly understood phenomenon. A number of longstanding questions related to CMV's role as a "driver" or "passenger" in the aging of the immune system, in age-related diseases and in complex comorbidities remain incompletely resolved and rather recalcitrant to being rapidly and conclusively resolved. Part of the obstacle lies in the complexities of longitudinal human studies, with pronounced ethical barriers and genetic and epigenetic variabilities on the one hand, and the imperfect concordance between human infection and more tractable animal models of CMV infection in a specific pathogen-free and genetically homogenized settings, on the other.