A Review of Cytomegalovirus in Immune System Aging

There is plenty of evidence to suggest that the persistent herpesvirus species cytomegalovirus (CMV) plays an important role in immune system aging. A majority of people carry the virus by the time they reach old age, and its presence causes an ever-increasing number of immune cells to become uselessly specialized to deal with CMV rather than able to respond to new threats. There are other contributing causes to immune system aging, but this seems like a potentially important one, for all that there is still work to be done to definitively prove the case. It is worth chasing this to a conclusion, because a state of too many CMV-specialized immune cells is reversible by the targeted removal of these cells, which will trigger their replacement with new non-specialized cells. This sort of approach has been demonstrated in laboratory animals for similar situations, and so is a possible tool for the rejuvenation toolkit.

As is the case for many potential causes of aging, it would be faster and cheaper to carry out destruction of CMV-specialized cells and then see what happens rather than to fully investigate all of the mechanisms and come to a conclusion without the data from such a prospective treatment. Nonetheless, the research community tends to take the latter rather than the former path. This open access review paper looks over what is known and still unknown about CMV in the context of immune system aging:

Immunosenescence, defined as the age-associated dysregulation and dysfunction of the immune system, is characterized by impaired protective immunity and decreased efficacy of vaccines. An increasing number of immunological, clinical and epidemiological studies suggest that persistent Cytomegalovirus (CMV) infection is associated with accelerated aging of the immune system and with several age-related diseases. However, current evidence on whether and how human CMV (HCMV) infection is implicated in immunosenescence and in age-related diseases remains incomplete and many aspects of CMV involvement in immune aging remain controversial.

After primary infection, CMV is carried for the lifetime of its host. Viral persistence is based on complex interactions between multiple viral and host determinants. These interactions generally result in a carefully negotiated and clinically "innocuous" balance between the virus and the immunocompetent host. Indeed, CMV rarely produces symptoms in the host unless the balance is upset by reduced immune competency of the host.

The co-existence of human CMV in healthy, and even more so, in elderly individuals is still a poorly understood phenomenon. A number of longstanding questions related to CMV's role as a "driver" or "passenger" in the aging of the immune system, in age-related diseases and in complex comorbidities remain incompletely resolved and rather recalcitrant to being rapidly and conclusively resolved. Part of the obstacle lies in the complexities of longitudinal human studies, with pronounced ethical barriers and genetic and epigenetic variabilities on the one hand, and the imperfect concordance between human infection and more tractable animal models of CMV infection in a specific pathogen-free and genetically homogenized settings, on the other.

Link: http://dx.doi.org/10.1016/j.exger.2014.03.020


Are you proposing a "reset" so to speak, where CMV cells are eliminated, new non-specific cells replace them, and gradually become CMV-specific again? Wouldn't this suggest that the host would experience the symptoms of CMV after those specific cells are eliminated? Is the line of thinking here that being "sick" while you build up immunity again is worth the potential gains of cells responding to new threats? I guess I am not clear on what would stop the new non-specific cells from responding to the most immediate threat - the one that is already present, i.e., CMV - and becoming CMV specific cells again, which would defeat the point of eliminating them in the first place. Thanks for the post!

Posted by: Heather Underwood at July 15th, 2014 10:55 AM

@Heather Underwood: Yes, a reset. The repopulation rate is apparently pretty fast in a healthy individual, on the order of hours or a few days. If it needed to be faster, then the treatment could be accompanied by delivery of patient-specific immune cells grown from the patient's own stem cells. Having a lack of immune cells should not be a problem in this context.

The effects of CMV on immune system aging appear over the course of decades, so resetting every now and then is not an unreasonable approach. Most of the science you find in SENS follows the idea that it's fine to let damage accumulate provided you remove it periodically, and this is just more of the same.

Posted by: Reason at July 15th, 2014 1:56 PM

It occurs to me that with a virus as widespread in the body as CMV, using the DRACO apoptosis anti-viral approach may be problematic. I wish I knew more about the possible interactions here - it would be unfortunate if DRACO could only be used in the young due to these kinds of persistent infections.

Posted by: Dennis Towne at July 16th, 2014 2:06 PM

Reason, what do you make of Dennis' concern? Would a person's cell repopulation rate be sufficient to tolerate widespread destruction of cells from DRACO treatments without excessive risk? Or would any DRACO patient need simultaneous stem cell infusions?

Posted by: Morpheus at July 16th, 2014 5:23 PM

@Morpheus: I don't know whether it is a concern or not. But let us look at the worst case, which is that you throw in stem cell or immune cell infusions immediately following the treatment. Bear in mind that the research community has for a decade now been running trials in which they destroy a person's immune system completely (via chemotherapy rather than a safer approach with targeted cell killers), and then repopulate it afresh from stem cells. So cell therapy replacement and augmentation of the immune system is technically possible now, and will certainly be much more practical in the near future if there is a more of a call for it.

Posted by: Reason at July 16th, 2014 5:40 PM

I believe they also essentially destroy the immune system in treatments for Crohn's disease.

Posted by: Michael at July 17th, 2014 11:05 PM

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