Impact of Lifelong Cytomegalovirus Infection on Aging

I don't normally point out funding press materials, preferring to focus on the other end of the research process, but this one, drawn to my attention by the Healthspan Campaign newsletter, contains a good overview of the current state of knowledge regarding the persistent herpesvirus called cytomegalovirus (CMV) and its role in immune aging. CMV is actually just about as innocuous and prevalent as herpesviruses get: most people are infected by the time they reach old age, and near all of them suffered no obvious and immediate consequences of that infection. Given the readership demographics here, I'd give even odds that you have CMV lurking in your tissues as you read this.

No obvious consequences is not the same as no consequences: the results of CMV infection are very real, just slow to appear. Like other herpesviruses, CMV can remain latent in the body and cannot be permanently cleared by the efforts of the immune system. One thesis on how it contributes to degeneration of the immune system is that ever more of the immune system's limited cohort of cells become specialized to attack CMV, with no resulting gain in that unending fight, leaving ever fewer cells able to tackle all of the other necessary tasks. In effect this is a sort of progressive misconfiguration of a programmable system, and a problem that might in the near future be addressed by selectively destroying these specialized cells. Some experiments conducted in recent years strongly suggest that this will spur the generation of replacement immune cells, and consequently a restoration of some lost functionality in the immune system.

This is a pretty compelling hypothesis given the evidence to date, but as for so much of everything that involves the immune system it is yet to be proven beyond a doubt. As for many of these sorts of things my preferred approach to investigation would be to fix the damage, here meaning removal of the CMV-specialized memory T cells, such as by adopting one of the targeted cell destruction technologies in the late stages of development in the cancer research community, and see what happens afterwards in tissue and animal studies. That of course is not the way things are done in the mainstream of research, where the tendency is to be much more conservative in adopting hypotheses for experimentation, and the first focus is on developing as complete an understanding as possible before building potential treatments. That may all lead to the same place in the end, or it may not - we shall see.

Impact of Lifelong Cytomegalovirus Infection on Aging and the Immune System Focus of UA Research

A virus that infects us when we're young and then hides in our cells throughout our lives without causing symptoms may weaken the ability of our immune system to defend against influenza, West Nile or other viruses as we age. "It is critically important to understand the causes and consequences of lifelong CMV infection for immunity and aging. CMV is present in 70 to 90 percent of people over 65, which by 2050 will translate into 70 million people in the United States and more than 1 billion people in the world." CMV has been associated with impaired immunity, increased morbidity due to cardiovascular diseases, and reduced lifespan and health span - the length of life spent in good health.

"Our research group recently showed that infection with only CMV, and no other acute or persistent viruses, causes defects in immune responsiveness to other infections and causes alterations in the naïve T cell receptor repertoire and impaired effector T cell responses. But the precise mechanism by which CMV affects naïve T cell responses remains incompletely understood. Our study seeks to define the cost, if any, of persistent CMV infection on immune function as we age and to begin to define ways to intervene against the negative effects of CMV in aging."

The adverse impact of lifelong CMV infection on the aging of T cells - a type of white blood cell essential to the functioning of the immune system - and the development of new immune responses could be due to a number of factors. "Improved control of CMV and/or reduction of CMV-specific [memory T cell] accumulation could be beneficial for immune defense, such as immune responsiveness to vaccination. But it is also possible that the virus actually helps the immune system in the younger age, while impairing it in older adults. The immune system works hard to keep the dormant CMV in check. We hypothesize that efficient CMV control will correlate with strong and successful responses to vaccination in humans and that individuals who use vast resources to control CMV will be less likely to respond well to vaccination."

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