Cytomegalovirus, CMV, is a prime suspect in one of the characteristic malfunctions seen in the aging human adaptive immune system. CMV is a very prevalent form of herpesvirus, and something like 90% of individuals test positive for exposure by the time old age rolls around. Most people have no noticeable symptoms of infection, and CMV is usually only a topic in clinical practice when it comes to immune compromised patients or transmission to unborn children, both situations in which infections largely harmless to everyone else can become a threat. While it is indeed largely harmless in the short term, like all herpesviruses CMV lingers latent in the body to emerge over and again to challenge the immune system.
The scenario suspected of CMV is that while its latent infection goes unnoticed in the vast majority of people, every time the virus emerges from hiding ever more T cells specialize as memory T cells that identify CMV. The immune system in adults has a low pace of replacement for T cells, and is effectively running in a capacity system: there are only so many cells to go around at any one time, and over the years ever more of that limited resource is devoted to CMV rather than to facing down new threats. At present this is a compelling hypothesis in the research community rather than a proven absolute. What is definitively observed in old people is an expansion of less useful T cells such as memory cells, a dysregulation of the immune system that occurs at the expensive of naive T cells and other types needed for a robust immune response. The immune system is complex and far from fully understood, and so there are competing explanations for this observation; pointing to the actions of CMV is one of the better supported hypotheses.
What to do about all of this? The engineering approach, which already has some backing from past animal studies, is to focus on selectively destroying the unwanted immune cells. They have a fairly distinctive surface chemistry, and the cancer research community is pouring a great deal of time and effort into the development of ways to safely and selectively destroy cells in living tissue based on these and other identifiable differences. If the misconfigured immune cells are cleared out, the hope is that they will be replaced with fresh copies that are not burdened by a lifetime of responding to CMV, and the immune system will be brought back into balance. The fastest way to quantify the effectiveness of this approach is to try it, given the technologies available today and the pace of discovery. Indeed, clearance of innate immune cells had this beneficial outcome in animal studies. Sadly there is all too little work on this front at the present time, as is the case for many of the more direct approaches to repairing the causes of age-related dysfunction and frailty.
Here is an interesting open access paper on a primate study of CMV, comparing two groups with and without exposure to the virus, that adds more supporting evidence for its role in immune system dysfunction in aging. The particular groups used perhaps offer a platform for further and more incisive investigations in the future:
The worldwide increase in life expectancy has been associated with an increase in age-related morbidities. The underlying mechanisms resulting in immunosenescence are only incompletely understood. Chronic viral infections, in particular infection with human cytomegalovirus (HCMV), have been suggested as a main driver in immunosenescence. Here, we propose that rhesus macaques could serve as a relevant model to define the impact of chronic viral infections on host immunity in the aging host. We evaluated whether chronic rhesus CMV (RhCMV) infection, similar to HCMV infection in humans, would modulate normal immunological changes in the aging individual by taking advantage of the unique resource of rhesus macaques that were bred and raised to be Specific Pathogen Free (SPF-2) for distinct viruses.
Our results demonstrate that normal age-related immunological changes in frequencies, activation, maturation, and function of peripheral blood cell lymphocytes in humans occur in a similar manner over the lifespan of rhesus macaques. The comparative analysis of age-matched SPF-2 and non-SPF macaques that were housed under identical conditions revealed distinct differences in certain immune parameters suggesting that chronic pathogen exposure modulated host immune responses. All non-SPF macaques were infected with RhCMV, suggesting that chronic RhCMV infection was a major contributor to altered immune function in non-SPF macaques, although a causative relationship was not established and outside the scope of these studies. Further, we showed that immunological differences between SPF-2 and non-SPF macaques were already apparent in adolescent macaques, potentially predisposing RhCMV-infected animals to age-related pathologies.
Our data validate rhesus macaques as a relevant animal model to study how chronic viral infections modulate host immunity and impact immunosenescence. Comparative studies in SPF-2 and non-SPF macaques could identify important mechanisms associated with inflammaging and thereby lead to new therapies promoting healthy aging in humans.