Cytomegalovirus Presence Expands Considerably in Old Age

The open access paper referenced here expands the picture of cytomegalovirus and the aging immune system with additional data. Cytomegalovirus (CMV) is a common herpesvirus present in near everyone by the time old age rolls around. In the majority of people it presents no symptoms, but it is apparently an important factor in the age-related decline of the immune system. Like all herpesviruses it cannot be effectively cleared from the body, and over the years the immune system devotes ever more of its limited resources to uselessly fighting it. An old immune system contains legions focused on cytomegalovirus and all too few cells capable of responding to other pathogens. This is one of the contributing causes of immunosenescence, the progressive failure of the immune system with age.

The best approaches to solving this problem actually involve expanding the population of useful immune cells rather than getting rid of cytomegalovirus. Clearing it doesn't fix the damage done: the specialized cells are already specialized. So possible treatments might involve delivering infusions of immune cells grown from the patient's own stem cells, selectively destroying cytomegalovirus-targeted immune cells to free up space for replacement with new immune cells, or restoring the thymus to increase the pace at which new immune cells are created.

Cytomegalovirus infection has been associated with a variety of health problems in elderly people and there is increasing interest in the mechanisms that underlie this association. A key determinant in this regard will be greater understanding of the balance of the viral load and the host immune response during healthy ageing. In this study we report, for the first time, that the level of cytomegalovirus viral load within the blood increased markedly in elderly people. A novel feature of our work was the use of digital droplet PCR (ddPCR) to provide an accurate quantitative measure of latent viral DNA. Previous methods for detection of CMV generally relied on nested PCR techniques, which made quantification challenging and also raised substantial problems with reproducibility.

Our work was performed using DNA isolated from monocytes, which are established as the most important haemopoietic site of viral latency. The first interesting finding was the observation that CMV was detectable in only a minority of donors, as 64% of people remained negative by ddPCR despite the presence of chronic infection as confirmed by CMV-specific IgG positivity. Indeed, in younger people below the age of 50 years, the detection of CMV load in the blood was uncommon, being observed in only 13% of donors tested. The lower limit of detection provided by ddPCR in our assay was for a single copy of virus within the total reaction volume and as such a negative result indicated absent or extremely low levels of virus. This low level carriage may reflect a lower intrinsic probability of viral reactivation in younger donors but is perhaps more likely to reflect the consequence of effective immune surveillance of viral replication in younger individuals.

The frequency of viral detection increased markedly with each decade above the age of 50 years to 37.5% and 50% and finally became positive in every donor who was older than 70. Interestingly the amount of viral DNA detected within the blood also increased substantially with age with a 29 fold increase observed between donors aged less than 70 and those over this age. The use of nested PCR also detected viral DNA within the majority of healthy elderly donors. These data indicate that a gradual impairment in the ability to control CMV load within blood starts around the age of 50 years and then deteriorates markedly beyond the age of 70. In conclusion, these data reveal the delicate balance that has evolved between chronic CMV infection and the host immune response and indicate that this symbiosis can break down during ageing, where an increase in CMV viral load occurs as the attritional effects of chronic surveillance and the impact of immune senescence become more apparent. It is likely that increased understanding of the clinical importance of chronic viral infection on human health will become an important health consideration in future years.



New reader here, thank you for the great up-to-date info you post. I'm fairly new to educating myself on current anti-aging research. This post makes me wonder again about something I have considered before. That is, whether viruses in our virome, or otherwise, contribute significantly to aging by simply out-competing our bodies for resources like amino acids as we get older and our immune systems fail to keep viruses in check. I wonder if viral load across the board mirrors the evidence shown here for cytomegalovirus, and whether it could be shown to correlate with any measurable deficiency? Are you aware of any studies that tested anti-viral meds for anti-aging properties?

Posted by: Chad at February 12th, 2016 4:04 PM


I have searched for those types of studies but haven't found any in healthy humans. I have read statistics that say the average lifespan in the US would be lengthened more by a cure for Cytomegalovirus than with a cure for cancer. Of course that is because almost everyone has Cytomegalovirus compared to a smaller percentage of people who get cancer. It does point to the importance of having a strategy which protects against viruses and aging of the immune system if you want to maximize your lifespan.

The two main strategies available right now that I am aware of are:

Use of Acyclovir/Valacyclovir which helps with Cytomegalovirus and is believed to actually clear the Epstein-Barr virus if taken long enough. In addition is also assist in decreasing the damage from other common viruses from the same family.

The other strategy is increasing FGF21. FGF21 which extends lifespan in mice by 40% protects against the loss of immune function that comes with age.

Posted by: Santi at February 12th, 2016 6:08 PM

ah thank you for the reply. I'll definitely look into those strategies more. Seems like it would be very straightforward to test anti-virals in aged mice for an effect on longevity, so I'd be surprised if it hasn't been done. I'll search for that as well when I get a chance and post back if I find anything.

Posted by: Chad at February 12th, 2016 8:58 PM

Very interesting. Just a side-effect of the immune system losing the plot with age, or a specific issue with CMV you think?

Posted by: ale at February 13th, 2016 6:37 AM

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