More Research into the Details of the Harm Done to the Aged Immune System by Cytomegalovirus

A fraction of the characteristic age-related decline and disarray of the immune system is due to long-term cytomegalovirus (CMV) infection. This herpesvirus is near ubiquitous in the population by the end of life, but for most people there are no immediate or obvious symptoms, or at least not beyond the slow corrosion of the immune system. CMV cannot be cleared from the body, but the immune system appears to devote ever more of its limited resources to this futile battle at the cost of its overall effectiveness. In the research paper noted below, researchers catalog more of the details of this process.

A robust therapy to clear CMV, were one developed, wouldn't fix the damage to the immune system created during the period of infection. One possibly alternative approach is to use targeted cell killing treatments to remove the specialized immune cells and free up space for their replacement, something that has been demonstrated to various degrees in the laboratory, but there is sadly little ongoing work here - the usual story for anything that might make a real difference in aging.

Aging and latent infection with cytomegalovirus (CMV) are thought to be major factors driving the immune system towards immunosenescence, primarily characterized by reduced amounts of naïve T-cells and increased memory T-cells, potentially associated with higher morbidity and mortality. The composition of both major compartments, γδ as well as αβ T-cells, is altered by age and CMV, but detailed knowledge of changes to the γδ subset is currently limited. Here, we have surveyed a population of 73 younger (23-35 years) and 144 older (62-85 years) individuals drawn from the Berlin Aging Study II, investigating the distribution of detailed differentiation phenotypes of both γδ and αβ T-cells.

This study presents a uniquely detailed analysis of the γδ T-cells, in younger and older people with a carefully characterized background. In the same subjects, we also assessed αβ T-cells, and found strong associations of CD8+ αβ T-cells, Vδ1+, other (Vδ1-Vδ2-) with age and also with CMV-seropositivity. The CD4:CD8 ratios were lower in old CMV-seropositive than in seronegative individuals. We found increased Vδ1:Vδ2-ratios associated with CMV in the old, similar to what is reported in cancer, supporting the theory of dual reactivity of γδ T-cells. It remains to be determined whether the increased Vδ1+ compartment in CMV-seropositive individuals might have similar detrimental impact as reported for the survival of melanoma patients. The memory differentiation patterns in the Vδ1+ compartment are similar to the CD8+ αβ T-cells markedly changed by age and amplified by the presence of CMV, suggesting an increased memory compartment of acquired immunity over the life-time and in particular in association with CMV. More functional and longitudinal studies are needed to better understand age-associated immune exhaustion and the role, if any, that a latent CMV infection plays therein due the major investment of immune system resources to maintain control of latent CMV.



'Little ongoing work' does this mean that the funding for Janko Nikolich-Zugich's group has run out?

Posted by: Jim at December 14th, 2015 10:19 AM

@Jim: No, it means you have to go digging to find more than one or two labs putting meaningful effort into that approach, and even there it isn't as though efforts and funding rises to the level merited by the potential benefits.

Posted by: Reason at December 14th, 2015 11:02 AM

Has there been any research yet that shows suppressive therapy with acyclovir or valacyclovir decreases the rate of damage done to the immune system by the cytomegalovirus?

Posted by: Santi at December 14th, 2015 4:23 PM

@Adam - It would be great if the Draco Indidgogo reached its target. Another potentially game changing technology that is somehow stuck below the level where companies would be interested in it.

Posted by: Jim at December 14th, 2015 5:28 PM

@Jim Thank you for your reply. I agree. Hopefully this is the first step in a slightly slower road to success, rather than a loss of momentum. There is an astronomical amount of purchasing occurring within the biotech sector and it is said to continue until at least 2020. DRACO has such potential to change the lives of so many, from young people with STD's, elderly individuals with shingles, and those in 3rd world countries facing viral epidemics. I would love to see one of the major industry players scoop this up and bring it to market. I guess the question is: Can they bring a cure to market profitably without crippling a treatment sector within their own operation that may be even more profitable than the cure? I hope for everyone affected, the answer is yes.

Posted by: Adam at December 14th, 2015 6:35 PM

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