Correlating CMV Infection and Markers of Inflammation in Older Individuals

Cytomegalovirus (CMV) is a highly prevalent herpesvirus, and cannot be effectively cleared from the body by the immune system. Nearly everyone is infected by the time old age rolls around. While most people have no obvious symptoms of infection, over decades CMV corrodes the immune system. Ever more cells of the limited number available to the adaptive immune system become uselessly specialized to fight CMV, which leaves ever fewer cells for other tasks. This is one of the contributing causes of immune system aging. A range of studies have demonstrated correlations between CMV infection and markers of immune system decline, such as chronic inflammation. The open access paper noted here is an example of the type.

What to do about CMV? A way to clear it from the body will prevent future issues for those who are young, but won't do much to fix the disruption of the immune system in those already old. Since CMV doesn't appear to cause much damage other than this slow breakage of immune function, it might be better to use targeted cell killing technologies to clear out the adaptive immune cells that are specialized to CMV, and then replace them via some form of cell therapy, or regeneration of the thymus, or another approach with a similar outcome of increased creation of new adaptive immune cells.

Aging has been linked to persistent low-grade systemic inflammation that is characterized by a chronic increase in the levels of circulating pro-inflammatory cytokines, whose presence is highly related to age-related metabolic, cardiovascular, and neurodegenerative diseases. To underscore the importance of pro- and anti-inflammatory homeostasis in aging, and the role of chronic low-grade inflammation in shaping the aging phenotype, a term "inflammaging" has been coined.

Cytokines are signaling molecules possessing unique modulatory functions. Among numerous pro- and anti-inflammatory cytokines, some stand out as influential contributors to age-related differences in health, immunity, and cognition. The tumor necrosis factor (TNF) that plays a key role in several neuroimmune functions is associated with the increased risk for neurodegeneration. IL-6 that is produced mostly by adipose tissue macrophages is elevated in persons of advanced age and people suffering from obesity. IL-10, an anti-inflammatory cytokine, suppresses, in turn, the release of TNF and other inflammatory cytokines. Another prominent pro-inflammatory cytokine, IL-1β is primarily produced by monocytes. Alone or in synergy with TNF, IL-1β affects nearly every cell in the organism.

To complicate matters, the interrelated effects of all surveyed cytokines as well as their influence on immune and neuroendocrine functions can be modified by chronic activity of an infectious agent. A lifelong persistent infection influences immunosenescence and can significantly alter the course of cognitive aging when it acts in conjunction with individual differences in cytokine production and release. Currently, consensus seems to be building around the CMV as such a chronic modifier of cytokine action. CMV exerts significant influence on the aging immune system and thus acts as a driving factor of inflammaging. In older adults, CMV has been linked to increased frailty, accelerated cognitive decline, and an increased risk of cardiovascular and Alzheimer's diseases.

The present study posited four major goals. First, we aimed to measure and characterize the baseline inflammatory status of aged individuals recruited for an intervention study of active aging before starting the cognitive and physical training. Specifically, we assessed main inflammatory and anti-inflammatory biomarkers, such as circulating cytokines. Second, we aimed to explore the influence of gender and CMV-seropositivity on the immune and metabolic markers measured at baseline. Third, we examined the associations among inflammatory and metabolic factors, and assessed whether CMV-seropositivity modifies these relationships. Fourth, we explored the influence of the measured inflammatory factors on the cognitive abilities, such as fluid intelligence, episodic memory, speed, and working memory, in the context of CMV-serostatus and gender.

In the present study we found that both gender and CMV-seropositivity modulate circulating peripheral biomarkers, and that CMV infection modifies associations among the latter. In CMV-seropositive individuals, episodic memory and fluid intelligence correlated negatively with pro-inflammatory IL-6; and episodic memory, fluid intelligence, and working memory correlated negatively with anti-inflammatory IL-1RA. We conclude that both CMV-serostatus and gender may modulate neuroimmune factors, cognitive performance, and the relationship between the two domains.