Are the Healthy Vulnerable? Cytomegalovirus Seropositivity in Healthy Adults Is Associated With Accelerated Epigenetic Age and Immune Dysregulation

BACKGROUND: Evaluating age as a risk factor for susceptibility to infectious diseases, particularly coronavirus disease 2019 (COVID-19), is critical. Cytomegalovirus (CMV) serologic prevalence increases with age and associates with inflammatory-mediated diseases in the elderly. However, little is known regarding the subclinical impact of CMV and risk it poses to healthy older adults. Prior to the COVID-19 pandemic we conducted a study to determine the association of CMV to biologic age and immune dysregulation. METHODS: Community-dwelling, healthy adults older than 60 years were evaluated using DNA methylation assays to define epigenetic age (EpiAge) and T-cell immunophenotyping to assess immune dysregulation. RESULTS: All subjects were healthy and asymptomatic. Those CMV seropositive had more lymphocytes, CD8 T cells, CD28(−) T cells, decreased CD4:CD8 cell ratios, and had higher average EpiAge (65.34 years) than those CMV seronegative (59.53 years). Decreased percent CD4 (P = .003) and numbers of CD4 T cells (P = .0199) correlated with increased EpiAge. CONCLUSIONS: Our novel findings distinguish altered immunity in the elderly based on CMV status. Chronic CMV infection in healthy, older adults is associated with indicators of immune dysregulation, both of which correlate to differences in EpiAge.