Subscribe to The Podcast by KevinMD. Watch on YouTube. Catch up on old episodes!

What if the real driver of aging isn’t your mitochondria or your telomeres but the tiny capillaries you never think about? Double board-certified emergency and internal medicine physician Kenneth Ro returns to the show to make a compelling case that microvascular decline is the overlooked upstream force behind nearly every disease of aging. In this episode, based on his KevinMD article “How the microvasculature drives the human aging process,” he explains why your body shuts down capillaries you stop using through a process called capillary rarefaction, and how that quietly starves tissues of oxygen long before symptoms appear. You will hear how microvascular disease connects diabetic complications, heart failure with preserved ejection fraction, and even sepsis under one unifying framework. He also shares why exercise works at a level deeper than most clinicians discuss, what GLP-1 agonists may be doing to your pericytes, and why VO2 max and heart rate variability are your best windows into microvascular health. This episode will change how you think about what it truly means to age well.

Tune into our episode “2026 Cholesterol Guidelines: LDL goals, lipoprotein(a), and coronary calcium scoring,” brought to you by Novartis Pharmaceuticals Corporation.

For the first time in eight years, LDL cholesterol goals have changed, and preventive cardiologist Seth Baum says the new guidelines are a long-overdue course correction. He breaks down the new LDL targets for your highest-risk patients, why the LDL hypothesis should be retired in favor of the LDL fact, why lipoprotein(a) screening finally belongs in every patient’s workup, what a coronary calcium score over 300 really means for how aggressively you treat, and how to talk to statin-skeptical patients without losing their trust. Listen now at KevinMD.com/cholesterol.

VISIT SPONSOR → https://kevinmd.com/cholesterol

Partner with me on the KevinMD platform. With over three million monthly readers and half a million social media followers, I give you direct access to the doctors and patients who matter most. Whether you need a sponsored article, email campaign, video interview, or a spot right here on the podcast, I offer the trusted space your brand deserves to be heard. Let’s work together to tell your story.

PARTNER WITH KEVINMD → https://kevinmd.com/influencer

SUBSCRIBE TO THE PODCAST → https://www.kevinmd.com/podcast

RECOMMENDED BY KEVINMD → https://www.kevinmd.com/recommended

Transcript

Kevin Pho: Hi, welcome to the show. Subscribe at KevinMD.com/podcast. Today we welcome back Kenneth Ro, emergency and internal medicine physician. Today’s KevinMD article is “How the microvasculature drives the human aging process.” Kenneth, welcome back to the show.

Kenneth Ro: Thanks, it’s great to be here again, Kevin. Thank you so much.

Kevin Pho: All right. So what led you to write this article and share it on KevinMD?

Kenneth Ro: Well, I really am an ER doctor, but I’m really interested in health, longevity. And there’s a lot out there, a lot of subspecialties. And I think physicians, providers, and patients, the general population, they have to be very confused because we all are. Lifestyle medicine, integrated medicine, precision, longevity, and everybody in those spaces are talking about kind of different things. It’s exciting, it’s new, and so a lot in the field, they’re talking about cellular biology and the mitochondria and cellular pathways. When I really sit back and look at it from a zoomed-out view, I really think a lot of it is looking at the trees instead of looking at the forest. The forest instead of trees.

But I love taking in all this. This is kind of like, it takes me back to medical school almost in my biochemistry days. I’m just like, well, these pathways are cool, but how can we really help people go towards health with these pathways? They’re important, but is it a little bit too much minutia? Is it too much rabbit holing? And of course, we all like to go down a rabbit hole, and we love this new technology and how we’re tracking it and biomarkers, but something kept nagging me saying, isn’t there something else that’s maybe a more unifying theme or might be a little more helpful for the general population and for our patients? So that’s kind of what led me to write the article.

Kevin Pho: All right, so tell us more about what you mean by microvasculature and its relation to aging.

Kenneth Ro: All right, so when you look at aging, everything just seems to decline, right? It’s like the odds are stacked against us. We try to put on more muscle, we try to exercise resistance training, but there’s anabolic resistance. There’s protein absorption decrease that happens while we age. Everything is just kind of stacked against us, right? We’re kind of fighting this uphill climb of sarcopenia and decline and osteopenia and loss of everything.

So I think a lot of the thought is, what is the aging process itself? We used to think it was just deterioration. Remember when we went to medical school, we were taught that the body creates senescence at the age of 30. After the age of 30, it’s all downhill. But now we know about neuroplasticity. We have seen people with broken barriers. Jack LaLanne, great example. One of my idols growing up. So the human capacity is not really tested either mentally or physically. And as society, we just keep lowering the ceiling and lowering the floor, accepting aging and kind of this fatalistic response to, on the one hand I’m getting older, and then on the other hand, there’s going to be some kind of procedure or pill that’s going to help me. That’s kind of the mindset that we have in our culture right now.

And so everybody’s looking for a quick fix. Everybody’s looking for a pill. But, Kevin, you can’t stent a capillary. When you really look back upon it, drawing on my experience as a physician, it’s staggering when you really think about how much microvascular disease you really see. It’s very evident in a diabetic. That’s all the end-stage problems for a diabetic, right? Neuropathy, nephropathy, retinopathy, it’s all microvascular. Now, heart failure with preserved ejection fraction, we used to call it diastolic dysfunction. We now know that that’s mostly a microvascular disease. Those people who get catheterizations, they have a no-reflow phenomenon. The bigger vessel might open up, but there’s no flow in the microvasculature.

So where does it really count in the body? It counts at the tissue level. And as an ER doctor, I can never overstress the importance of oxygen and oxygen delivery to the tissues. We’ve got four minutes of no oxygen to our brain before we’re brain dead. That’s got to supersede mitochondria and pathways, because if you don’t have the substrate, if you don’t have the supply of oxygen, which is vital for life, all these other processes aren’t going to work.

So with that framework, I started looking into maybe something different as far as something we should concentrate on. And a couple of things came up. First of all, you notice how exercise is beneficial for almost everything. For decreasing the aging process, for muscle building, for decreasing Alzheimer’s risk, for depression, you name it. Exercise is helpful. But the question is, why is that? People I think kind of drift into thinking it’s a mitochondrial issue. Well, when I really looked into it, it seemed like it was more a microcirculation issue.

One of the big turning points too is that there was a Nature article looking at GLP-1’s effects on the body. And they zeroed in on the capillaries, the little organs, the little cells that create capillary either vasodilation or vasoconstriction. For viewers, most of us know this, but some might not, back to your training medical school days, the arteries and the arterioles have vaso and muscular linings. That create either opening or closing. Capillaries don’t have that luxury because they’re so small. Only one red blood cell can fit through a capillary, right? So they have these cool little cells on the outside called pericytes. Not to be confused with parasites obviously, but those are the guys that actually open or close the capillary.

And what GLP therapy has found is that they have had a lot of surprises in medicine as far as positive effects. Everything from reduced cardiovascular endpoint events, MACEs, to even improvements in osteoarthritis, which led us to kind of say, well, arthritis is not just a degenerative mechanical problem. There’s something going on inflammatory as well and other cytokines. And then there’s just this whole Pandora’s box that GLP-1 agonist therapy, along with SGLT2 inhibitors, has shown. It’s not just decreasing glucose. It’s not just decreasing weight. There’s something else that’s going on.

So then when I kind of mix that in with exercise, I kept coming back to the microcirculation. In medical school, capillaries, you can remember the picture of arterioles, the big capillary bed, and the venules. And that’s all the training we got in capillaries and microcirculation. We’re more enamored with the big arteries, the coronary arteries and the aorta and all the other structures that we could actually see and dissect in anatomy. So I firmly believe we take that same kind of bias into our medical careers.

But the one thing that really highlights it for me is shock. Shock is defined as decreased oxygen delivery to tissues. It can come in many different flavors, obviously. Cardiogenic, neurogenic, distributive, and including septic. Now there’s a huge awareness about sepsis in medicine, particularly in the ER and in the hospital. But essentially what sepsis is, it’s leaky capillaries. The capillaries are not delivering the oxygen to the tissues, and that’s causing a whole cascade of cellular dysfunction and even death. So I was trying to just maybe, maybe it’s not about the mitochondria, maybe it’s something a little more upstream. And that’s what made me really kind of start to focus on the microcirculation.

Kevin Pho: So in your article you link microvascular decline to inflammation. So in terms of the chicken and the egg, in terms of the studies and evidence that you looked at, the microvascular decline, is that more a consequence of aging? Or is that more a cause of aging? What does the evidence say?

Kenneth Ro: I think it’s very, it’s kind of 50-50 chicken-egg. You can make the distinction either way, but the concept, well not the concept, but what the body does is something called capillary rarefaction. And that is essentially the essence of, if you don’t use it, you lose it.

Your body is a resource manager. Your brain is a resource manager. And over time, if you’re not using something in your body, your body’s going to say, OK, well, we don’t need to allocate those resources to this particular part of the body, be it maybe the hamstring or a calf or something like that, because we’re not really using it that much. So the body will, to match the resources and to maintain homeostasis, it will, our bodies will start shutting down capillaries. And of course that’s going to happen as we age.

So I think it’s more of an issue of input. And that input is going to be either maintained or possibly enhanced as time goes by, or it’s going to decrease. So it’s kind of like looking at an X and a Y axis, and if you’re not going to use something, then we’re not going to allocate those resources to use it because we’ve got to use these resources somewhere else.

Kevin Pho: So translating what you said into practical action. What are some things that people listening to you could do to optimize their microvascular circulation, assuming that it would help slow down aging? Or what kind of advice that I can give as a primary care physician in the exam room to optimize microvascular health?

Kenneth Ro: OK. So the main thing is, of course, just good old-fashioned movement. But the movement has to be planned. It has to be consistent. And there is a certain point where it has to be a little bit of a challenge. You have to really get to a point where, and there’s so many protocols out there, high intensity, altitude, zone two, that’s another rabbit hole you could really just get yourself down into. But it goes to the old adage that something is better than nothing. You have to do something.

And in this age, I think one of the best devices is, if you want to get something done, start off with the morning. It doesn’t have to be a massive gym session or a bunch of sprints, but at least a morning walk. Blood flow restriction bands, I think, will end up being very helpful because that produces a hypoxic environment and then creates kind of a stimulation for the microcirculation. And then of course, nitric oxide is very important within the endocalyx and increasing capillary blood flow. So anything that will enhance nitric oxide. So guys, if you’re already on Cialis once a day for your BPH and your ED, that actually helps your microcirculation. Arginine, beets, those sort of compounds do help your nitric oxide. So that’s all very helpful.

But I think it’s just being aware of how important it is so that you just put that in your conscious awareness and say, OK, yeah, this is important. Because literally, it’s pretty straightforward. Use it or lose it. So let’s start using it every day. And make it fun, make it to where you’re using it, doing things with other people. Then you get the connection, then you get the benefits of exercise. Dr. Gundry will recommend getting a dog because he has four dogs. So obviously that gets you up and about without you talking yourself out of doing something, or you’re just outside walking with your dog. But anything, the importance of movement and exercise, I think the take-home message is, why is exercise important? This is why exercise is important.

Kevin Pho: Any way to objectively measure microvascular health?

Kenneth Ro: I think VO2 max is still our best objective measurement. And there are wearables, the Apple Watch, a Whoop, can kind of approximate it. Of course, the best way to do it is formal testing in a lab. It could be tacked onto your treadmill, or out of curiosity, you can get it for maybe $100, $150, but it really should be tracked every year. And like I said, the wearables can track it and they’re getting better and better. But definitely VO2 max, that’s the efficiency of the extraction of oxygen and the efficiency of your cardiovascular system. That’s a very good measure.

Another good measure of how well your microcirculation is doing, in my opinion, because it’s also tied into your autonomic nervous system, is your heart rate variability. And also HRV and HRVC, both of those are very important because that kind of measures your capacity. So when you have more capacity, when you have more nutrients going to the tissues where you need it to go, going to your brain, going to your heart, going everywhere, that just gives you more energy and makes you feel more alive, makes you more vibrant, and just makes everything better.

Kevin Pho: So in terms of things that we can do, we could measure it with VO2 max and some of the metrics that you mentioned. Obviously exercise or planned intentional exercise. And then you did mention therapies like GLP-1 agonists and SGLT2 inhibitors. As far as any role that they play, perhaps in the future, do you know if studies are going on that would prospectively measure microvascular health with these medications?

Kenneth Ro: I think that’s kind of the way we’re going. Here’s kind of where we stand in medicine. We’re kind of getting out of threshold medicine, waiting for a hemoglobin A1C to be above a certain level. I think really in true precision or preventative or whatever kind of medicine you want to call it, I just call it good common-sense medicine, because we’re trying to improve health span and help people become more vital. One of my pet peeves is pre-hypertension, pre-diabetes. Well, your hemoglobin A1C is not quite high enough, so we don’t need to really start medications. Let’s do lifestyle first. I totally disagree with that. I understand it from a population point of view, but I think there will be studies where we will start treating people with some of these medications, maybe at different dosages, just to increase their metabolic health. And a big portion of that is the microcirculation.

Kevin Pho: We’re talking to Kenneth Ro, emergency and internal medicine physician. Today’s KevinMD article is “How the microvasculature drives the human aging process.” Kenneth, let’s end with some take-home messages that you want to leave with the KevinMD audience.

Kenneth Ro: I think we can kind of focus on how important exercise is. We talk about it and everybody is just, it’s one of those things where I think people want to procrastinate on exercise and sleep. But one thing I want to just pass along is that, don’t compare yourself to somebody else. Just get out there and do it because it’s enjoyable, it’s fun, and kind of hardwire it into your day. So instead of going straight to your computer, instead of doom scrolling your phone, give yourself a little extra time just to put that phone down. Wake up in the morning, get outside, do a 15-minute walk. Maybe do some calisthenics. It’ll make a huge difference in your day, I promise.

Kevin Pho: Kenneth, as always, thank you so much for sharing your perspective and insight. Thanks again for coming back on the show.

Kenneth Ro: Thanks a lot, Kevin. Always a pleasure.