John Whyte, MD, MPH: Welcome everyone to the WebMD Health Discovered podcast. I'm Dr John Whyte, WebMD's Chief Medical Officer. We all age, but how and when has been a bit of a mystery. New research though helps shed some light on aging and it might even challenge our conventional wisdom. To help explain it all is my guest, Dr Michael Snyder. Dr Snyder is Stanford Ashman professor and the director of the Center of Genomics and Personalized Medicine at the Stanford School of Medicine. 

He's a leader in the field of functional genomics and proteomics and one of the major participants of the ENCODE project. His laboratory study was the first to perform a large-scale functional genomics project in any organism and has developed many technologies in genomics, so I know he is the person to talk to.

 Welcome to the WebMD Health Discovered podcast, Dr Snyder.

Michael Snyder, PhD: Oh, it's great to be here.

Whyte: You know, at WebMD, we always like to say, “better information leads to better health,” and that's what we try to do. Try to empower people with good health information. And I know you're a big proponent of health information and you really have this compelling health journey of your own.

So before we get into the issue of aging, I wanted to ask a little About your health journey.

Snyder: Well, as you point out, we're very big on taking deep data on people with the idea of health monitoring at a level that's never been done before. And in my case, we started this project about 15 years ago now. on me and then the smallest group of around 110 people. And we've been following them for quite some time.

And in my case, it turned out to be incredibly valuable in the sense that my genome predicted as high risk for diabetes, which was a surprise at the time. And then once you know it, I actually got diabetes. It was discovered during this profiling period. And so that was predicted from the genome and by doing the steep data, we discovered that.

And then I also discovered when I first got Lyme disease of all things with a simple smartwatch and a pole sock. So, we think this health monitoring could be super, super powerful on me. It's been powerful at least twice in my life.

Whyte: What did your smart watch tell you that kind of gave you a hint?

Snyder: Yeah, two things. One is that my resting heart rate went up and it turns out I was wearing a pulse ox as well. My blood oxygen dropped and that was the first clue. It was all pre symptomatically, meaning I saw these changes before symptoms appeared and told me something was up. And then I did get symptoms off and on and was diagnosed ultimately as Lyme disease.

Whyte: That is interesting. Well, let's turn to the topic of accelerated aging and I know you're not a huge fan of that term but there's been a lot of publicity around this recent study that talks about that we tend to think we age in this linear pattern, right? As we get older, we tend to age kind of like a car. The longer we have the car, the more problems that occur.

But some research suggests that there are these bursts of aging, and they may occur in the 40s and they get in their 60s. So, talk to us about this concept.

Snyder: Yeah, so it's exactly what you say. Everybody assumes that we just gradually age and then pass away. So, we decided to see, well, are there changes, what changes are occurring as people go through these various age periods. So by following this group of people, we actually follow them longitudinally.

And then we also did the analysis, what's called cross sectionally. We basically discovered that. People don't just, you know, age gradually that some things, there are all kinds of biological processes that occur at different times, but we asked where the most changes are occurring. And once you know, it was in the 40s, early 40s, and actually in the 60s, now the 60s we expected people know that already.

There's something called sarcopenia where you lose muscle mass, your immune system declines. That's why we get vaccinations when we hit our 60s. So that was kind of expected. We did discover things a lot more than was known because we are doing these deep data dives on people. Meaning we saw that, oxidative stress, other sorts of things were happening in the 60s, that weren't as well, in fact, kidney decline seemed to be occurring in the 60s.

So, we saw things that weren't necessarily known. The one in the forties was not expected necessarily. I think at sight, you can kind of rationalize that people do get, you know, kind of hurt themselves athletically as they hit their forties. We know that anecdotally, but we could see that we could see changes in muscle and, components as well as, other things as well.

Whyte: And you said early forties, you saw some of this data. 

Snyder: Yeah, around 44 is where it's centered, but it's a broad range. But yeah, we saw changes in lipid metabolism and the hindsight. I think that makes sense with people's fat distribution shifting and you know, lipids start going off. And that was one thing we saw changes in alcohol metabolism, caffeine metabolism hitting in the forties.

So that was a bit unexpected. And I think the information is useful. 

Whyte: Then what's happening in the fifties? I have to ask.

Snyder: You know, your carbohydrates are shifting a bit. Carbohydrate metabolism, oxidative stress. Some of these things are occurring throughout your life, but these are these forties and sixties are periods where their particular bursts of changes, if you will. 

Whyte: And that's important information for people to know. And we'll talk about why that's important. But I also want to ask you, how do people recognize the signs of this perhaps quicker aging, right? Because as we age, there are normal signs of aging that, you know, are the shape of our cornea changes and in terms of how we see in terms of our hearing, what should people be aware of?

Snyder: Yeah, I don't think we measure ourselves enough to be perfectly honest that it's when you're healthy people usually don't go to see a physician So I think that would be lesson number one I think people should really get monitor a lot more frequency so you can measure your cholesterol or your glucose Especially your glucose you may know the 12 percent of the U.S. is diabetic and 33 percent and that more now are pre-diabetic and most of them will become diabetic in the future if not within five years. So, we have a diabetes crisis that's out there that most people are ignoring, and they're not even aware. Most pre diabetics don't know it. 90 percent don't know it.

So, I think just getting yourself measured, checked up, see what your glucose looks like. And there are new ways of doing this. They're continuous glucose monitors that will actually track your glucose every five minutes. And you can see, it turns out it's really interesting, different foods spike different people.

And so, we all have our own personal patterns. what foods you eat spike your glucose may not be the same as those for me. In fact, they won't be. And so, knowing that's super important because then you can, eat the foods that don't spike you and avoid those that do.

And it doesn't mean you, you don't eat things you like, you just eat healthier things specifically for you. I think getting yourself measured, knowing that kind of information, and we're in a world where we can now do this. One thing our lab happens to do, we discover a lot of things and then we spin off companies.

So, it's been off one of these continuous glucose monitoring companies. It's called January. We've also spun off another company that does metabolic testing. It's called IOLO. We're the old test in a at home sample. He gives a little drop of blood. I know what this sounds like, but it does work. You give a little drop of blood, and we'll measure 600 analytes, and you'll see and it covers all kinds of things. Inflammation, oxidative stress, all sorts of things that are useful. 

Whyte: How often should we be thinking about that though? We tend to think it's the yearly checkup, which some people don't even get. And they go every other year or every couple of years. As we approach our forties, given this research around accelerated aging, should we be going in once a year, every other year, or is this concept of continuous monitoring?

You mentioned CGMs, Continuous Glucose Monitors. You mentioned, you know, smartwatch, the smartwatch and other wearables can collect continuous data. So, what should we be utilizing, Dr Snyder, as we know this new data about aging? 

Snyder: Yeah, I think some of these continuous monitors everybody should be wearing. So smart watches. Now I'm overboard. You can see my three 

Whyte: How many do you have on?

Snyder: Yeah, three watches. I often wear four. One broke. I have a ring that measures, believe it or not, I normally wear.

Whyte: It might be a little bit too much [laughs].

Snyder: Yeah, I don't think you need all these now. I'm a scientist. I'm trying to read, you know, use them all to figure out which one's best and what, how, what frequency these devices should be tuned at and things like that. So, but the average person just needs one, but they're very valuable. You'd be amazed. So, we can tell you when you're getting COVID on average, three days in advance of symptoms.

Whyte: And especially looking at trends, like you mentioned, your heart rate was higher than usual. So maybe sometimes the exact number for wearables is we shouldn't, you know, hang our hat on, but we should look at trends. Is that something that you recommend to people?

Snyder: Absolutely. So, it's really critical. You know, your baseline so that you can see shifts from your baseline and our baselines are all different. Our resting heart rate different. Our blood oxygen, everything about us is different from one person to the next. So, knowing your baseline so you can see a shift from that baseline is absolutely key.

And that's how I figured out my Lyme disease. That's how we now detect when people are getting respiratory viral infections. This will be the future. You'll be able to tell mental stress from a simple smart as well. We've in fact shown that, that when people, get, stressed at work and you will actually pick that up. And so, we think this kind of information is very, very valuable. 

Whyte: What about these tests that I see advertised that can tell me my biologic age versus my chronologic age, or they could tell me the age of my heart and my brain in theory that could be useful information as we talk about accelerated aging, but do we have enough data right now to do that? 

Snyder: Yeah. And in fact, that's one of the things we discovered from our research as because we're tracking people over time, we can see how they change and which we interpret as aging. And it turns out that everybody ages differently. Some people are cardio agers, some are immune agers, some are metabolic, some are all of the above.

And knowing that is very, very valuable because the information is actionable, 

Whyte: Do we have a good way to know that right now for the general consumer?

Snyder: Well, we first discovered this through our research we literally measure 135,000, take 135,000 measurements every time we sample someone. So, we'll follow the microbiome and, you know, as many molecules out of their blood and urine as possible.

And so, we do see what changes are occurring. And that information, as they say, depends from one person to the next. So we now have spun off a company on this, that one I mentioned earlier, Iolo. They actually will follow 600 metabolites, and they'll not only tell you your overall biological age relative to your chronological age, meaning you might actually be older or younger than your actual age in years, but they'll tell you exactly what's going on, like your, your oxidative stress Actually, you're older and you're oxidative stress or inflammation, and that information is very, very valuable, and this is where AI kicks in.

You can collect information that's out there in the literature, but also combine it with information around yourself and actually make good, you know, I think solid recommendations. And it's not just exercise more, eat better. It's very specific. You should eat better. You know, if your oxidative stress is off, they'll tell you five things to eat.

And I'm a big believer in that. So if you're tracking yourself, you can see what's shifting in an adverse direction and take action.

Whyte: Yeah. What about the role of physical activity? Would we change the physical activity based on this information? Should we be doing different types of exercises in our forties and our sixties?

Snyder: Yeah, I believe absolutely. So in fact, that's the number one thing I recommend for living a long, healthy life. And most people in the longevity field will say the same. Exercise is number one. So I exercise every day. and to be honest, I do strength training because Those shifts we were seeing in the 40s and 60s, muscle was one of the top items there.

And there's something called your extracellular matrix proteins and key muscle proteins that are shifting during those times. So, and it's very clear as people hit their 60s, they get sarcopenia and you know, that's a problem. And exercise makes all these beneficial hormones, they call them myokines and things like this are really, really good for your health.

And keeping your muscle mass up is really important. So, you know, this advice that when people, turn 80 and you say, well, grandpa, it's okay. Take it easy. Sit down. That's actually bad advice. You actually want them to keep moving because that will keep their health up. And I think it's just good for your vascular and your microvascular system.

So I'm a big believer in not just exercise, but strength training in particular for the muscle mass. we don't know why they're the big changes in the forties. My guess is as people hit their thirties and forties, they probably aren't getting as much exercise or nutrition, and they have a lot of other life stresses that are hitting.

And that's probably why some of those shifts, including muscle mass shifts are occurring then too. So I'm a believer you should keep it up your whole life. I myself was a runner for a long, long time. and I'm a type 2 diabetic. I'm a weird one, and I shifted from running to weight training to increase my muscle mass.

Now, in my case, it didn't work because I'm a weird diabetic, as they say. Muscle mass, increased didn't help, but I keep it up anyway because I think it's just really, really good for your health. 

Whyte: We'll call it unique, A unique type of diabetic. 

Snyder: Yeah. 

Whyte: Now, what about the role of sleep as we age, recognizing these births in the forties and the sixties? Should we change our sleep patterns? 

Snyder: Getting a good night's sleep is really important. It's not an area we've been studying much, but we're starting to do a lot there now. So, most people tell you, get at least seven or eight hours. And as you get older, people have a tendency to sleep less. And that's actually not good. And there's strong, we have some studies showing it correlates with increase in sleep.

Glucose dysregulation, meaning diabetes and prediabetes, likely to happen if you don't sleep as much. 

Whyte: And some of that is because as we get older, we have less time in deep sleep and we might have early awakening, but you're suggesting that we still focus on that seven to nine hours of quality sleep every night, especially as we get older.

Snyder: Yeah, you're right about that. That deep sleep and REM sleep is generally the prevailing wisdom is both. Those are important. So, yeah, you, quality of sleep counts for a lot too. And so this idea of how, you know, you should really should.

Stay dark and watch out for, you know, blue light and that sort of thing. It's real. I mean, you should really try to sleep and sleep continuously if you can. So you can hit those stages. 

Whyte: You know, as physicians, we tend not to talk to our patients about aging. Using that term, we tend to talk to them about, you know, their health and their conditions. But something I find that I want to ask you about is, sometimes when I'll talk to patients, they'll be like, Oh, Dr Whyte, my mom's in her 90s and doing great, so I don't have to worry.

And other people do get concerned when their parents die in their 50s, and it's kind of a wakeup call to them. And this kind of is that age old question, what's the role of genes, genetics versus lifestyle?

How do they play into how we age? We know they play some role, but do you have a better quantification of how much they play?

Snyder: Yeah, there's a lot of studies around this now. There's some disagreement, but the overall average is about that genetics accounts for about 16 percent of your life span, most of what your life span is dependent on environment and lifestyle. So you really have more control over your, lifespan than you think you do.

Now, it's true for people who live to be 100 or older, that number is more like 60 percent, meaning so to be a centenarian, you do need good genes, And even for centenarians, know, living a long, healthy life has other factors.

And in fact, if you look at people who live in the blue zones, they have several things in common. One is they're all physically active. Second, they all have pretty good nutrition and Mediterranean diets, one form of that.

There are other forms of a healthy diet as well. They're generally low and ultra-processed foods and things like that. And they have good social networks actually. So socialization is a very, very important part of longevity. So we think it's important that you do all of those and, and sleep has not been incorporated as much, but I, I think most of us think they probably sleep pretty well too. 

Whyte: And they have this sense of real community in their areas where they're physically getting together and looking after each other. It's not all virtual time and, you know, they're social friends on various platforms. I have to ask you about the role of stress and how stress factors into this. If you are very stressed, would that accelerate your aging even more or to a greater degree?

Snyder: Yeah, there are several kinds of studies out there that have shown that, you know, mental health stress actually does accelerate aging and certainly other kinds of stress too, like cancer and things like that, physical types of stress, disease stress will also accelerate aging as well. So, yeah, certainly on the mental health side, I think keeping a good healthy, balance and, you know, your mental state is very, very important for your health and for longevity.

Whyte: Are there any biomarkers or any specific test that our audience could ask their doctor about today to have a better sense of where they are in aging? Sometimes we talk about, you know, C reactive protein, you know, somewhat nonspecific. There's some other ones that have been in the news. What should people know?

Snyder: Yeah, great question. I think most markers are disease markers. You mentioned CRP for inflammation, things like that. And so I think we need better health markers to be honest. There are some simple things that people do, but they're not perfect, like grip strength or the ability to get up off the floor. Believe it or not, there's a few physical things where getting up off the floor without your hands, that's harder than you think as you get older. 

There's something called epigenetic clocks where you can look at your modified DNA. They're actually fairly accurate, believe it or not, for telling your biological age. and they can certainly measure that. Now, the epigenetic clocks aren't so actionable. The ones I mentioned earlier with metabolites and things like that.

They're better. I think because they give you information you can act upon. so I think the field will add more of these markers, but It is a problem. We don't have as many good markers for aging as you like, and gray hair is not a good one.

Whyte: Now, since we have this information about these points of accelerated aging, should people think about vitamins or minerals during those times? Do you take any vitamins? 

Snyder: Yeah, believe it or not, I take about 10 things. I obviously take things for my diabetes. That's been important for keeping that under control. But when it comes to supplements I'm a beliver in several kinds. Antioxidants, so I take, cytochrome, vitamin C is a good antioxidant. 

Anti-inflammatories, I'm big on those. So turmeric and things like that are good examples . I, believe it or not, I take these things that make nitric oxide beetroot extracts. 

Whyte: And everyone should talk to their doctor about these beforehand because even though they're over the counter, they can interact with some prescription medications as well. You know, there's been some discussion about certain drugs. You know, metformin has been in the news in the past about aging. There's been other ones. How would you quantify this body of research? Is it not yet ready for prime time? Is it we're almost there? We have enough kernels right now. So, listeners can say, you know what? I need to go do these things.

Snyder: I would say it's early days. There's still lots to learn and we are learning. There's getting to be science around these things now, which is what we really need, of course, to make this stuff work. 

Whyte: Should we change screening guideline if we know these times of accelerated aging, should we rethink when we screen people for cancer? 

Snyder: Oh, for sure. Yeah, I would argue we don't even know how often we should screen people. And so, your question earlier about, you know, what should we be doing and how often? Well, I think a smart watch is an easy thing, or a ring that tracks your heart rate and all that. There's a lot of powerful information around resting heart rate, heart rate variability.

You may know in the rings these days, they do blood oxygen and they do things that we don't do in a doctor's office that are valuable, so they're powerful. But then what? What about other things? Well, I would argue, you know, one reason I like this home sampling. I like the idea of getting measured every three months with some simple tasks that aren't expensive, that could tell when things are shifting off.

And that's turned out to be valuable in our research study where we'll see people shifting. We'll catch it right away and we'll make recommendations that bring him back into a more healthy range. and I think if it's cheap and easy, people do it. Okay. But people don't like to go to a physician's office.

It's always inconvenient, when they're healthy. so they tend to go when they're sick. So I like the idea of a lot of this home testing, which I think the field will move more and more towards. And I think that'll be valuable. 

Whyte: I have to say, Dr Snyder, I love your comment about that too often we only get measurements of our health when we're sick, and that's when we go to the doctor, and we need to change our concept of health and aging to think about how do we get more information when we're healthy to continue to promote that health. So, I'd love to close our interview with some actionable steps from you. You gave us a bunch over the last 20-25 minutes, but if people had to prioritize in terms of what they could start doing today with this information that we have these bursts of aging at different times in our 40s and our 60s, what would be your recommendation to them?

Snyder: Number one is exercise. And I, as you heard already, I'm a big believer in strength training. Keep your muscle mass up because people, their health just plummets once they lose mobility. So I would argue, you know, keeping active super important. We talked about nutrition with the antioxidants, the anti-inflammatory and other things, you know, these omega threes that generally viewed as useful.

So I think a good diet and definitely watch out for the ultra process for foods, the cakes, the sweets, and you may not know we eat 40,000 times more sugar now than we did after the end of World War II. It's ridiculous. So we've got to cut back on that sugar as my lesson there. And I think having good social community, as we talked about earlier, super important. And we mentioned sleep as well. I think all four of those ingredients are key to living a long, healthy life. 

Whyte: Well, those are a lot of good tips, and I want to thank you, Dr Snyder for being with us today and really explaining this research around accelerated aging and what we can do about it. And be sure to check out Dr Michael Snyder. You can find him at Stanford, and definitely want to look at his latest research and thank you all for listening.

Please take a moment to follow, rate, and review this podcast on your favorite listening platform. If you'd like to send me an email about topics you're interested in or questions for future guests, please send me a note at [email protected]. This is Dr John Whyte for the WebMD Health Discovered Podcast.