Q&A: Even mild COVID-19 cases may accelerate aging process

A recent study published in Frontiers in Genetics found that even mild cases of COVID-19 may speed up the body’s rate of aging, although receiving a COVID-19 vaccine might reverse these effects.

In a retrospective, non-randomized study, Florence Comite, MD, a precision medicine clinician-scientist, founder of the Center for Precision Medicine & Health and CEO of Groq Health, and colleagues analyzed DNA methylation states in 21 study participants before and after mild or moderate SARS-CoV-2 infection to investigate how the virus and messenger RNA vaccination might impact methylation patterns and epigenetic clocks.

According to the researchers, there were significant differences in DNA methylation after SARS-CoV-2 infection, which suggests that aberrant DNA methylation states related to COVID-19-induced immune dysfunction might produce an immune cell-based epigenetic signature. The findings also “suggest that the epigenetic aging signal related to COVID-19 exposure is driven by changes in blood immune cell type composition” — something even more pronounced in older patients, the researchers wrote.

For people aged 50 years or older, Comite and colleagues found that SARS-CoV-2 infection increased epigenetic age by an average of 2.1 years. After vaccination with the Moderna vaccine, however, biological aging captured by an epigenetic clock was significantly decreased by an average of 3.91 years.

Healio spoke with Comite about how SARS-CoV-2 affects the aging process and the vaccine’s mitigating effects.

Healio: How does SARS-CoV-2 speed up the aging process? What are the underlying mechanisms?

Comite: The major trend is that the aging response to COVID is different for people and actually seems to be triggered by chronological age. That's an important concept. But I think underlying it is the immune system. There are a few aspects of it. When you're young — and that's 30, usually — your body is going to be at its peak. By the time you hit 30, things are beginning to decline under the surface, and by the time it gets to 50, there are ongoing disorders of aging that are undermining. Even if we feel okay, maybe symptoms haven't fully emerged. So, the immune system is really behind this whole mechanism of why the aging process may increase during COVID.

Healio: When patients hear “speeds up the aging process,” they might be concerned about how that will affect their lives. What kind of impact might this have on a patient’s health?

Comite: I think that the impact might be a wake-up call more than anything. Once you know that maybe time changes things — and we all kind of know that intellectually, maybe, but we don't feel it until we're hit with an illness and we watch other people around us get sick and don't get well or die, even, and that happened very dramatically during COVID.

I got COVID right away in March 2020. I came back from a meeting in California and ended up with COVID after a 36-hour trip. I remember watching the news and feeling so sad because, underneath, our system is beginning to deteriorate. That kind of impact — knowing that psychologically may help individuals say “I'm going to take care of myself better. I want to figure out why if I'm at risk for disease.” For example, if a mother has diabetes or a grandfather has a heart attack, am I following in their footsteps? Who in the family do I resemble? So, health declines, but you don't necessarily feel it, and it starts emerging with symptoms, but addressing it before you get sick is probably the best method. Taking care of yourself to optimize who you are and how you feel beginning in the 30s always would be great, but since we take it for granted until we're about in our 30s, 30s is really probably a great place to start.

Healio: Are certain patients more likely to be affected?

Comite: In general, what happens in the immune system is that, when you get an infection, the number of T cells might have increased the ability to improve aging post-vaccine. There are two aspects to the study. There’s one aspect to the study where getting COVID alone affects you; the other aspect is what vaccination does.

By interacting through the immune system, we’re possibly improving aging, but it could be a transient effect. And then in other folks, it would be helpful maybe to understand that, under 50, you get this increase in protective cells in the blood whereas, in contrast, those over 50 years of age, we saw a significant decrease in the percentage of CD4 and T cells in the blood following COVID-19. So, I think that by recognizing where you are not only on the chronological age curve, but biologically, we think of age in different ways.

The most important way to think of age is how old are we really, cellularly. Speaking in terms of not the number of candles we blow out on the cake, but rather the health we own and the optimal health. Therefore, invest in yourself in terms of your health. Because as we age, it's inevitable that we will decline and usually we wait because our health care system is about disease care, not really health, and we don't get taken care of or even see our doctor sometimes until we're sick. So, ideally, it's a way to think about ‘how do I stay healthy?’ And start thinking about this in my 30s and 40s as, below the surface, your health is beginning to decline. And I think the end organ effect — meaning it all accumulates in the immune system, and that is really what we want to keep strong. For example, it's getting enough sleep because clients who sleep adequately — and adequately means different for everybody because we look at an n of one effect. That's a unique way we think about the system: that each one of us is unique. But figuring out how much we need to take care of yourself and feel good is an important component.

Healio: How does COVID-19 vaccination help reverse the body's epigenetic age?

Comite: The number of B cells after infection might have caused that improved aging rather than a true aging signal, so that we don't yet know whether it's something that we can count on seeing again when we continue to test people or if it's transient. So, if you're in good shape and you're younger, you're going to have an immune system that can rise to the occasion of an infection — whether it's COVID or anything else, like the flu — and in general, your response will be better. And in doing so, that contributes to what the aging number was in our study. And yet, after 50 — and we happen to use 50 as a marker; remember, this is a small study, there aren't a ton of patients here — but after 50, our body may tackle the immune system. We know that's true. We know that, in acute COVID, the second half of the infection when you have inflammatory disease, that's where people begin to decline. They don't do as well. So it may be that the immune system can rise to battling an infection even after 50, but then doesn't recover as quickly, even perhaps alluding to the incidence of prolonged or long COVID.

Or another factor in our system is what other issues are going on under the surface; that our immune system may be distracted. So, when someone gets sick with COVID and they are diabetic, they were four times as likely to need a respirator. If they were a diabetic, but it had never been diagnosed — and diabetes shows up when you get sick, particularly when 80% of diabetics are actually diagnosed in the ER — then they're going to go downhill faster, and they don't know they have diabetes. So, understanding that there is an improved response and folks survive after infection, but their immune system may have taken a hit and it's hard for it to recover the older or sicker somebody is.

Healio: Would additional boosters help the age-reversing process?

Comite: It's likely to make a difference because that's what our study showed, even with a few numbers. But the few numbers work against us because we have no way to be able to tell if this is a true anti-aging prospect. I think it’s absolutely worth studying, and we're going on to do that, but there's lots of ways to help the age-reversing process before you would get COVID or a booster.

Healio: What are the clinical implications of your findings and the take-home message for primary care physicians?

Comite: More needs to be done to validate the findings, given the limited number of participants. Again, the decrease might have been due to changes in the immune cell composition rather than the actual aging signal. But what's impressive is that the PCPhenoAge class significantly increased in those over 50 years of age. In contrast, of course, to observations of those under 50 years of age where the PCPhenoAge would decrease. And that's fascinating. If we go on to look at what the implications are, it is monitor and take care if disorders run in your family like disorders of aging — which I consider to be diabetes, cardiovascular disease, Alzheimer's, bone loss, cancer — then address them find out what biomarkers you might be able to actually utilize as a marker of health. And that is really critical. And recognize from the physician point of view that there are immune biomarkers and function that can be measured that can help prevent decline whether it's with COVID, cancer, or any other condition like diabetes, heart disease, stroke, that a person is at risk for. We have studied this extensively the last 20 years and have data here at the Comite Center that that show us that we can actually optimize health and reverse those biomarkers, which you can recognize even in a 20-something but certainly by 30-something, there's beginning to be real findings that will progress into disease.

Healio: What are the next steps of your research?

Comite: Our work really focuses on what I think of as ‘n of 1,’ meaning each of us is unique. I happen to be born an identical twin, and so as genetics became available, I realized that my twin and I were very different, which means that the way medicine is generally practiced is more ‘one size fits all.’ And we believe that it's important to know thyself, if you will, to be able to direct the choices you make. For example, for sleep, for the food you eat, or for exercise, or even restorative kind of practices like meditation, which can decrease cortisol, which can decrease sugar and decrease weight — mainly visceral fat. And all of that will help. And an individual can own that in some ways, and we are measuring all of those factors, as well as what supplements can make a difference and what medications may be necessary, because we have even very young folks who have a genetic makeup that means they have carbohydrate craving, and we need to understand how that might impact putting on weight, never being able to lose it no matter how well you eat or work out. There are factors that that kind of undermine you and how we can best help people take care of themselves. So, the next steps of our research are to continue to collect data to make it tighter with higher numbers, but also to see what are the factors that can mitigate change over time; stop what we call the disorders of aging progression.

Our goal is to collect more n of one data, which we do at our centers. We have centers that have been doing this work since I was at Yale. I started at Yale, and I continued to do that work and the data is phenomenal where we see people deaccelerate aging and literally get biologically younger so their cells are younger under the surface and we can measure that epigenetically by looking at 100,000 variants on your genetic makeup, even as they blow out more candles on the cake.

Healio: Is there anything else you’d like to add?

Comite: One final thing would be the notion of personalized precision medicine. So, to take care of yourself before symptoms emerge. Because under the surface, we know at 40 or 50 or 60, we're no longer 20 or 30, and each one of us has their own future health trajectory by owning data, by actually collecting data, which is what this study represents, and marrying that data, which I think of as precision. So, the data that we collect makes it more precise, and marrying that to who you are as a person. I think of it as a health story.

We can actually induce change in folks because there are never going to be enough doctors. We're never going to know everything there is to know. But the more we have in terms of actual data, which I think goes as vision — below the surface things we may not see with their eyes, or even know what's happening until we get a heart attack or diagnosed with cancer. And the more we know ourselves and we can turn to our family to get that information we can absolutely, as a physician, turn to our patients and say, “let's see what's going on in your family history. Let's understand your potential for the future.” Because, in this day and age, we don't really have a family doctor. They don't exist. We tend to use urgent care. In the old-fashioned days, a family doctor might not have all these tools and these studies we can do, but they knew you and they knew your family. I think that's where we're seeing the future of medicine emerge. The digital health market, the data that we can collect and actually make a difference in the way we live life. Who wants to live life getting ill or not feeling well? I think we all want to live life to the fullest.