Cytomegalovirus Infection Accelerates Age-Related Epigenetic Changes

Cytomegalovirus (CMV) is one of the most prevalent of the many forms of persistent herpesvirus that our immune system cannot effectively clear from the body. It has few obvious immediate effects in most people, and you probably never noticed when you were first infected. The overwhelming majority of people test positive for infection by the time old age rolls around. There exists a range of fairly compelling evidence to suggest that long-term CMV infection is a primary cause of immune system dysfunction in aging, and the paper linked here adds to that collection. There are only so many immune cells that can be supported at once by our adult biology, and an ever larger fraction of this capacity becomes uselessly specialized to CMV, unable to respond to new threats. The best treatment for this problem isn't to get rid of CMV, as that probably won't greatly help people with very damaged immune systems, but to remove the unwanted immune cells and replace them with fresh new cells that can do their jobs.

Epigenetic mechanisms such as DNA methylation (DNAm) have a central role in the regulation of gene expression and thereby in cellular differentiation and tissue homeostasis. It has recently been shown that aging is associated with profound changes in DNAm. Several of these methylation changes take place in a clock-like fashion, i.e. correlating with the calendar age of an individual. Thus, the epigenetic clock based on these kind of DNAm changes could provide a new biomarker for human aging process, i.e. being able to separate the calendar and biological age.

Information about the correlation of the time indicated by this clock to the various aspects of immunosenescence is still missing, however. As chronic cytomegalovirus (CMV) infection is probably one of the major driving forces of immunosenescence, we now have analyzed the correlation of CMV seropositivity with the epigenetic age in the Vitality 90+ cohort of birth year 1920 (122 nonagenarians and 21 young controls, CMV seropositivity rates 95% and 57%, respectively). The data showed that CMV seropositivity was associated with a higher epigenetic age in both of these age groups (median 26.5 vs. 24.0 in the young controls and 76.0 vs. 70.0 in the nonagenarians). Thus, these data provide a new aspect to the CMV associated pathological processes.


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