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Current Opinion in Immunology 2009, 21:440–445 Biomarkers of human immunosenescence: impact of Cytomegalovirus infection Evelyna Derhovanessian, Anis Larbi and Graham Pawelec Lay summary Age-associated failing immunity, or “immunosenescence”, contributes to the increased incidence and severity of infectious disease in old people. Which of the multitude of ageassociated alterations thus far reported are causally-related to a person´s health and longevity is not known. If we could identify the mechanisms of immune ageing and intervene to restore appropriate immunity, a long healthy lifespan might result. This is, however, an enormous current challenge in a very long-lived species like humans. Circumstantial evidence and longitudinal studies limited to the very elderly have begun to reveal “immune signatures” or biomarkers of immune ageing consisting of several parameters which we have designated the “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.