Biomarkers of human immunosenescence: impact of Cytomegalovirus infection

Age-associated failing systemic immunity, loosely termed ‘immunosenescence’, is thought to contribute to the increased incidence and severity of infectious disease in old people. It would therefore be of great practical as well as academic interest to accurately identify which of the multitude of alterations to immune parameters thus far reported are causally related to a person's clinically unfavourable health status, in order to identify the mechanisms of immune ageing and intervene to restore appropriate immunity. This is an enormous current challenge, as it requires longitudinal studies in a very long-lived species. Circumstantial evidence and longitudinal studies limited to the very elderly have begun to reveal ‘immune signatures’ or biomarkers of immune ageing consisting not of a single parameter, but clusters of parameters increasingly recognized as an ‘immune risk profile’, or IRP. Although hinted at many years ago, a marked impact of usually asymptomatic infection with the persistent β-herpesvirus Cytomegalovirus (CMV) on markers of immunosenescence is now becoming incontrovertible. The fascinating cohabitation of CMV with the human immune system, which commits a very significant fraction of its entire resources to CMV-immunosurveillance, may suggest an early-life benefit from infection, which becomes deleterious for the majority of the population only in later life or under pathological conditions.