Telomere attrition associated with herpesvirus infections

Their findings were recently published in the Journal of Infectious Diseases.

The medical significance of a virus such as cytomegalovirus (CMV) that infects many, but seems innocuous due to a lack of symptoms in those who are seropositive, is hard to pinpoint. Several recent studies unearthed associations with certain viruses and an increased mortality rate among those who were seropositive for the virus being examined. One of the potential mechanisms by which herpesviruses contribute to cellular aging is examined in the study by Dr. Dowd et al.

The determinants of telomere attrition, a potential marker of cellular aging, are not well understood. Persistent herpesvirus infections including CMV infection may be particularly important for telomere dynamics via mechanisms such as inflammation, oxidative stress, and their impact on peripheral blood lymphocyte composition. This study examined the association of 4 human herpesviruses (CMV, herpes simplex virus type 1, human herpesvirus type 6, and Epstein-Barr virus) with change in leukocyte telomere length (LTL) over 3 years in 400 healthy individuals (aged 5376 years) from the Whitehall II cohort.

CMV, herpes simplex virus type 1, and human herpesvirus 6 infection were independently associated with greater 3-year LTL attrition, with no association found for Epstein-Barr virus, and a particularly strong effect found for CMV, which has previously been implicated in immune aging. The magnitudes of these associations were large. On average, those who were CMV positive showed telomere shortening that was the equivalent of almost 12 years of additional chronological age compared to those who were CMV negative. Seropositivity to more herpesviruses was additively associated with greater LTL attrition (3 herpesviruses vs none, β = −0.07 and P = .02; 4 infections vs none, β = −0.14 and P andlt; .001). Higher immunoglobulin G antibody levels among those seropositive to CMV were also associated with shorter LTL at follow-up. These associations were present after adjusting for age, sex, employment grade, body mass index, and smoking status.

Dr. Dowd discusses the significance of these findings, “This study was the first to investigate the role of persistent herpesviruses in accelerated aging as measured by telomere length. Telomeres are the physical structures that cap and protect chromosomes, and their shortening has been proposed as a marker of cellular aging. The mechanisms underlying differences in telomere length across individuals is not well understood, but we hypothesized that infections that have been shown to play a role in inflammation and immune aging may play a role.”These results suggest that exposure to infectious agents should be an important consideration in future studies of telomere dynamics.

The significance of herpesvirus infections may crossover into non-biological health determinants as well. Dr. Dowd explains, “Our previous research has shown that CMV seropositivity is more common among those of lower socioeconomic status, suggesting that CMV may be one biological mechanisms responsible for SES disparities in health and aging.”

Jennifer B. Dowd, Jos A. Bosch, Andrew Steptoe, Bamini Jayabalasingham, Jue Lin, Robert Yolken, Allison E. Aiello; Persistent Herpesvirus Infections and Telomere Attrition Over 3 Years in the Whitehall II Cohort, The Journal of Infectious Diseases, , jix255, https://doi.org/10.1093/infdis/jix255