Early-life environment influencing susceptibility to cytomegalovirus infection: evidence from the Leiden Longevity Study and the Longitudinal Study of Aging Danish Twins.

Human cytomegalovirus (CMV) is a common herpesvirus establishing lifelong persisting infection, which has been implicated in immunosenescence and mortality in the elderly. Little is known about how and when susceptibility to CMV infection is determined. We measured CMV seroprevalence in two genetically informative cohorts. From the Leiden Longevity Study (LLS) we selected long-lived sib-pairs (n=844) and their middle-aged offspring and the offspring's partners (n=1452). From the Longitudinal Study of Aging Danish Twins (LSADT) 604 (302 pairs) same-sex monozygotic (MZ) and dizygotic (DZ) twins aged 73-94 years were included (n=302 pairs). Offspring of the long-lived LLS participants had significantly lower seroprevalence of CMV compared to their partners (offspring: 42% vs. partners: 51%, P=0·003). Of 372 offspring living with a CMV-positive partner, only 58% were infected. The corresponding number for partners was 71% (P<0·001). In the LSADT, MZ and DZ twins had high and similar CMV-positive concordance rates (MZ: 90% vs. DZ: 88%, P=0·51) suggesting that shared family environment accounts for the similarity within twin pairs. Our findings suggest that susceptibility to CMV infection--even under continuous within-partnership exposure--appears to be more strongly influenced by early-life environment than by genetic factors and adult environment.

Senescence of the human immune system.

The umbrella term 'immunosenescence' is applied to describe age-associated failing systemic immunity and is believed to contribute to the increased incidence and severity of infectious disease in old animals and people. Very limited studies in man have begun to reveal biomarkers of immune ageing ('immune signatures') increasingly recognized as an 'immune risk profile' (IRP) predicting mortality in the elderly. Even more limited studies in companion animals seem consistent with the idea that most or all other mammals may also show an IRP. It is of practical and scientific interest to more accurately determine the IRP and to devise interventions to modulate immune ageing. In man, cytomegalovirus (CMV) infection has an enormous impact on biomarkers associated with immunosenescence; it is not clear whether the same is true for a persistent viral infection in other animals. A significant fraction of the human immune system is committed to controlling CMV; this commitment increases with age and may itself cause pathology as a result of maintaining higher systemic levels of inflammatory mediators. It will be interesting to test whether similar phenomena occur in relatively long-lived animals, often sharing a human environment, like cats and dogs, and whether interventions to restore appropriate immunity in companion animals might also be applicable to people.