How to Measure Biological Age with John Wilkins, MD

“Our hope is to pretty rapidly move into interventional studies where we're going to see, are there lifestyle interventions? Are there pharmacologic interventions or others that can slow or maybe reverse biologic aging in some individuals?” - John Wilkins, MD  

• Associate Professor of Medicine in the Division of Cardiology 
• Associate Professor of Preventive Medicine in the Division of Epidemiology 
• Associate Director of the Human Longevity Laboratory 

The Potocsnak Longevity Institute at Northwestern University Feinberg School of Medicine has launched the Human Longevity Laboratory, a longitudinal cross-sectional study that investigates the relationship between chronological age and biological age across different organ systems and aims to validate interventions that may reverse or slow down the process of aging.  

• Over the last several years, there has been a flattening of the curve when it comes to life expectancy, and potentially even a decline due to cardiovascular risk determinants. Simultaneously, chronic non-infectious diseases have become far more prominent in recent years, becoming the number one cause of mortality. 
• The Potocsnak Longevity Institute, run by Douglas Vaughan, MD, is a multifaceted institute focused on how to understand mechanisms of human aging, the burden of aging and age-related diseases on a population level, as well as the development of interventions that can slow the rate of aging, and maybe even turn back the clock for some people. 
• The Human Longevity Lab investigates the best ways to measure biological aging: how does biological aging vary within different organ systems within an individual? How much does it vary in an individual over time? And how much does it vary across individuals? 
• In contrast to chronological age, biological age is defined by the rate of age-related tissue or organ dysfunction, and whether that dysfunction is greater than what one would expect based on how long someone has been on the planet.  
• One of the best ways to measure biological age is by measuring epigenetic age. Wilkins and his team are developing other systems of measurement as well, such as looking at the proteome, cardiovascular aging, cognitive function, lung function, among many others. 
• Wilkins and his team are particularly interested in participants of the study who have been subject to adverse social determinants of health as well as those who are HIV positive, which increases the rate of biological aging. 
• Within the next few years,  Wilkins would like to pivot to interventional studies, including rigorous randomized controlled clinical trials in humans.  
• Wilkins envisions the development of multi-nation, interventional studies, including a network of longevity labs around the world, to understand aging within broader cultural contexts.  
• Recruitment for this study is underway and people interested in participating can fill out this participant interest form. 

Additional Reading

• https://pubmed.ncbi.nlm.nih.gov/38639077/
• https://www.feinberg.northwestern.edu/research/podcast/2023/alcohol-impacts-aging.html
• https://magazine.nm.org/2024/07/16/turning-back-the-clock/

Recorded on June 7, 2024.

Target Audience

Academic/Research, Multiple specialties

Learning Objectives

At the conclusion of this activity, participants will be able to:

1. Identify the research interests and initiatives of Feinberg faculty.
2. Discuss new updates in clinical and translational research.

Accreditation Statement

The Northwestern University Feinberg School of Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

Credit Designation Statement

The Northwestern University Feinberg School of Medicine designates this Enduring Material for a maximum of 0.25 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

American Board of Surgery Continuous Certification Program

Successful completion of this CME activity enables the learner to earn credit toward the CME requirement(s) of the American Board of Surgery’s Continuous Certification program. It is the CME activity provider's responsibility to submit learner completion information to ACCME for the purpose of granting ABS credit.

All the relevant financial relationships for these individuals have been mitigated.

Disclosure Statement

John Wilkins, MD, has received consulting fees from 3M. Content reviewer, Nilay Shah, MD, MPH, has nothing to disclose. Course director, Robert Rosa, MD, has nothing to disclose. Planning committee member, Erin Spain, has nothing to disclose. FSM’s CME Leadership, Review Committee and staff have no relevant financial relationships with ineligible companies to disclose.

[00:00:00] Erin Spain, MS: This is Breakthroughs, a podcast from Northwestern University Feinberg School of Medicine. I'm Erin Spain, host of the show. There are many reasons why some people seem to age faster than others: genetics, lifestyle, environmental factors could all play a role. But what if there was an intervention that could slow down biological aging and help us all live longer, healthier lives? A team of Northwestern medicine scientists think this is possible. The Potocsnak Longevity Institute at Northwestern University Feinberg School of Medicine has launched the Human Longevity Laboratory, a longitudinal cross-sectional study that investigates the relationship between chronological age and biological age across different organ systems, and aims to validate interventions that may reverse or slow down the process of aging. Joining me to talk about the launch of this fascinating study is Dr. John Wilkins, associate Director of the Human Longevity Laboratory and Associate Professor of Medicine in the Divisions of Cardiology and Preventive Medicine at Feinberg. He's also a cardiologist at Northwestern Medicine. Welcome to the show. 

[00:01:21] John Wilkins, MD: Thank you. Nice to be here. 

[00:01:22] Erin Spain, MS: Dr. Wilkins, can you talk to me about aging. Now we're able to live so much longer than even our great, great grandparents. Give me an overview of where we've been, where we're going when it comes to aging. 

[00:01:35] John Wilkins, MD: We've definitely seen substantial changes in survival time over the centuries, and we've seen real shifts actually in what people die from over time. So, 19th century, right? People were more likely to die of things like infectious diseases, accidents, et cetera. There was a lot more obviously infant mortality. As we progressed into the 20th century, we did see a little bit of a transition towards people dying of more chronic diseases. We're seeing this now worldwide, that these sort of chronic non-infectious diseases are taken over, as a number one cause in mortality. These are often diseases related to cardiovascular health. And certainly we're seeing, you know, increases in cancer-related mortality as well. So we've seen this sort of increase in life expectancy. However, more recently you've probably seen that we're starting to see a flattening, if you will, of the curve, so to speak. And maybe even a decline in life expectancy, we think related essentially to obesity and overnutrition. So overall I'd say, last few hundred years, we've generally seen an increase in life expectancy, but I think due to some less favorable trends and release cardiovascular risk determinants, we're starting to see that that slow or maybe even go the other direction, where life expectancy is going to shorten now. Our understanding of what aging is changes every day. And the rate at which we're developing new knowledge just seems to just keep increasing and increasing and increasing over time. More recently we even have this concept that, you know, age is more than just years that you live on the planet. There are kind of rates of molecular, cellular tissue and organ dysfunction with time that can be slowed by potentially even intervening on these fundamental molecular, biochemical, cellular kind of mechanisms of age. 

[00:03:13] Erin Spain, MS: Talk to me a little bit about this idea that we want to optimize our health as we age. 

[00:03:19] John Wilkins, MD: I'm a clinical cardiologist, and I do a lot of work in prevention and when I talk to people about optimizing their lifestyle or treating their risk factors, some patients push back at me and say, you know, Dr. Wilkins, I gotta die of something. And I say, that's true. You're right. The question is, number one, how healthy do you wanna be before you die? And then they go, oh yeah, I guess I don't wanna be sick, you know, for a long time. 

I mean, if you gave me a choice, you said, you know, John, do you wanna live to 95 and be sick for 10 years before or do you wanna live to 95 and get really, really sick at 94 and three quarters and you know, die a few months into some illness? I'd say I take the latter. I mean, who wouldn't, right? With the Human Longevity Lab, I mean, that's one of our main objectives is to help people live more of their life healthier. And we think that intervening on biologic aging can be one of the things to do that. We'd like to extend the overall lifespan as well. But I think you can do both. In fact, I think in order to extend lifespan, you have to extend healthy longevity. 

[00:04:13] Erin Spain, MS: So the Human Longevity Lab. This is a project, as I mentioned, out of the Potocsnak Longevity Institute here at Feinberg. First, set the scene for us. Tell us about this Institute. It's fairly new. It recently opened in 2022. 

[00:04:26] John Wilkins, MD: So, the, Longevity Institute that's run by Dr. Doug Vaughan, and it is a, sort of multifaceted institute obviously that is focused on human aging, how to understand mechanisms of human aging, understand kind of the burden of aging and age-related diseases on a population level, but also, trying to develop interventions that can slow the rate of aging, maybe even turn back the clock for some people. We'll see. And with a particular focus actually on groups of individuals that are disadvantaged from an aging standpoint. So for example, that might be people living with chronic infections like HIV. In fact, we know and have known for years now, that HIV, chronic HIV infection, accelerates the rates of biologic aging. And also looking at populations of people who have a high burden of adverse social determinants of health. So these might be people living in conditions with chronic stress, right, or living in environments that may have other factors that may accelerate biologic aging. For example, things like indoor air pollution. You know, housing quality, I mean, you name it, there's a long list. And so that's sort of the overall, the overall Institute. And the Human Longevity Lab is again, one component of that where we're really focused on understanding what are the best ways to measure biologic aging. How does biologic aging vary sort of within different organ systems within an individual? How much does it vary in an individual over time? And of course, the obvious question is, is how much does it vary across individuals, at any given age, how much of a spread do we see in these various measures of biologic age. So there's a lot of really fundamental questions that need to be answered first. And then our hope actually is to pretty rapidly move into interventional studies where we're gonna see are there lifestyle interventions? Are there pharmacologic interventions or others that can slow, again slow, or maybe reverse, you know, biologic aging, in some individuals. 

[00:06:23] Erin Spain, MS: We've talked about this term biological aging. So explain to us the difference or the relationship between chronological age and biological age. Just kind of lay that out for us and, why this intersection of chronological and biological age is so central. 

[00:06:37] John Wilkins, MD: Well, the concept of chronologic age is fairly straightforward. That's just the number of years since you were born. A biologic age is more of a nuanced construct. I think probably the most general or sort of safest definition for it, if you will, is the rate at which there's age related tissue or organ dysfunction, and is the amount of, let's say, dysfunction in a cell, tissue or organ greater than what you would expect based on how long someone's been on the planet. That would be an accelerated biologic age versus the inverse, which is what I think we all hope for ourselves and what we'd like to restore in more people is where we're seeing a slower rate and decline in cellular tissue in organ function over time. But I think what you're getting at, that question is, well, okay, John, what's the best way to measure that? And, and that's one of the fundamental questions that we're trying to answer. I think most people understand that one measurement is just not gonna tell you all you need to know. And, that actually, is one of the reasons we've designed The Human Longevity Lab the way we have. And, we really take a multidimensional approach to characterizing biologic aging. One of the most well-known, I'd say, indices or measures of biologic age is something called epigenetic age. Epigenetics refers to the field of sort of DNA modification that does not change the base pair sequences. So it's not like a variant, or mutation is the old term we used to use, in the sequence of your base pairs in the DNA. It refers to other modifications. And specifically for epigenetic age, we're talking about methylation. Okay? So these are little chemical groups, methyl groups, that get added in specific locations on the DNA. And it turns out, over time, the DNA becomes more methylated in specific patterns that indicate biologic age. We can measure an individual's DNA methylation, at least from cells obtained from their blood. And from that, these different patterns of methylation can predict chronologic age. And there's another, they call these things clocks in quotes. And then there's other epigenetic clocks that are trained to associate with chronologic age, things like outcomes, like probability of developing a chronic disease or a probability of death over a certain time horizon. So that's one type measure that's sort of more of a molecular measure. We're developing or others have developed. And we're gonna be incorporating, you know, measurements, looking at the proteome, or all the proteins that are present in a given sample of blood. How does that give us insight into somebody's biologic age? We can look at how proteins are, specific proteins are modified interestingly. There are different other chemical groups that kind of get stuck on proteins over time. That also, specific proteins, that can predict how well your proteins, how durable they are, how well they fold, things like that. You can look at metabolic differences. And then we really spend a lot of time looking at organ specific measures. Dr. Vaughan and I are both cardiologists, so we certainly have that bias. And so we do a lot of measurements of cardiovascular aging. So we take an EKG. From an EKG, we can derive using actually AI based technologies, We make measurements of arterial stiffness. We make measurements of how well your arteries dilate actually, which is a measure of something called endothelial function. We look at how much your heart rate varies actually over several minutes. And it turns out that a higher amount of this heart rate variability is something we tend to see more in younger individuals, and that decreases as people age, or throughout their life course. Those are just some examples. And then we're measuring cognitive function, lung function, also overall functional status. So how far does someone walk in six minutes? And then, we're also taking videos of how people walk. You've seen people walk and thought to yourself either, that's a walk of someone who looks more frail, a way an older person might walk. And we're really trying to study that and working with some of our colleagues at Shirley Ryan Ability Lab to really understand that in more detail. 

[00:10:28] Erin Spain, MS: Can you tell me so far, have there been big differences that you've seen in individuals between biological and chronological age? 

[00:10:35] John Wilkins, MD: It depends. So there are some individuals where we have, number one, seen differences between different biologic aging measures, right? So they're ECG age, maybe, different from what we would expected looking at their vascular function, for example. Not wildly different, but they don't line up perfectly. Most people that have come through the lab, actually their biologic age has been younger than their chronologic age. 

[00:11:01] Erin Spain, MS: And then there's probably folks on the other end of the spectrum too. What have you seen as far as an outlier where their biological age is much higher than their chronological age? 

[00:11:10] John Wilkins, MD: I haven't had people be much higher. I've had people be maybe a few years older than their chronologic age. Let's say you're 20 and you come in and it says your biologic age is 22. And this is what types of questions we need to answer. Is that indicative of an early life age acceleration? Or maybe there's more error in our assessment of biologic age in people who are 19 to 22 or there's less of a spread, right? Like the difference between a 19 and 22-year-old is so small that you're more likely to kinda misclassify them. Whereas, you know, I think you've, I'm sure seen this like as people progress to middle age, then you start to see that some people look older. Like you see that 40-year-old that you're like, Hey look, 50 or that 40-year-old, they're like, I thought they were 25. And I expect we're gonna see the same thing with these sorts of biologic age and chronologic age differences or acceleration or deceleration of aging, is gonna be a little bit more stark as people get into middle age and beyond. 

[00:11:57] Erin Spain, MS: So you're recruiting people for this study right now. Tell me about the experience that you're creating for the participants and how you walk them through being a study participant.  

[00:12:07] John Wilkins, MD: We are recruiting, although thus far we've not had to do a lot of recruiting. People have been coming to us. We have a list of I think 2000 people who want to participate. And that doesn't mean others shouldn't reach out if they want to participate. 

[00:12:18] Erin Spain, MS: Well, you're also looking for some very specific populations that you're recruiting as well, people who may be HIV positive... 

[00:12:22] John Wilkins, MD: Adverse social determinants of health too, right? And, and so you have to be really, intentional, about your recruiting strategy. I do wanna make the point that we're actually interested in aging across the life course. we're talking young adulthood, 18, all the way to the extremes of age. Because actually, you know, interestingly, aging occurs throughout the life course, aging starts at birth. In fact, it might even start in utero, interestingly, And so, again, we're interested in aging of the aged, but we're also interested in like understanding some of the more subtle markers, right, of aging that you may be able to find in young adults if you look carefully. And, you know, can we intervene on that, right? To change their overall life trajectory. From a cardiovascular space, I've also been particularly interested in prevention in young adults, so this kind of melds with my other kind of world of research. 

[00:13:06] Erin Spain, MS: Northwestern is really uniquely positioned to do this. So we have the Institute. There's also been a lot of studies taking place really over the past several decades looking at aging. Douglas Vaughan, the director of the Institute, has worked with Amish populations where he found, really an anti-aging variant. We did a podcast with him a few years ago about that study. There's also the SuperAger study at Northwestern, which is really investigating people who are living extraordinary lives into their older years. Just tell me about the environment at Northwestern and what makes it such a good spot to study aging. 

[00:13:41] John Wilkins, MD: So it's a sort of a perfect opportunity to have people kind of come together under the umbrella of this Institute, to really optimize biologic insight and optimize our science. So I think that's definitely one of the factors. I think another is that we just have had a very supportive environment, and Northwestern's willingness to set up things like institutes, this Institute of aging, right? Having the infrastructure there, right? To do the science and do the research that you need to do is enormously important. And we've had that support. We've also received philanthropic funding, notably from the Potocsnak family, to make this happen. And, and that's, obviously essential to make these types of efforts work. 

[00:14:13] Erin Spain, MS: Let's talk about the long-term goals. So right now you're in this recruiting and data collection mode, and you're building this cohort and these amazing, rich profiles of human health. What do you see happening in the next five to 10 years with this project? 

[00:14:29] John Wilkins, MD: So I'm gonna speak to the Human Longevity Lab. In our first year, maybe a year and a half of research, our goals are really a little more observational, right? So we're really focusing on these kind of fundamental questions that I brought up earlier, like, okay, for a group of people, how much variation do we see between, let's see your measures of cardiovascular aging, versus your functional measures versus your measures of molecular aging. Right? Very kind of basic question, but you need to understand that in order to move to our phase two, which I'll talk about. Another question is, how much change do we just see in people over time, if you don't intervene, other than letting them know some of these measures, right? Like what happens? And then, the third of course being, let's say any group of 40 year olds, how much variation do we see across groups of 40 year olds, right? So that's a lot of our these initial data that we need to generate for the lab. And I think one of the really unique things about our group is that we're studying humans and we wanna pivot very quickly again to interventional studies. That's our goal. We talk about a two to five year goal. That's what we wanna be doing in that time period. And really doing rigorous, randomized controlled clinical trials in humans, and you know, any of these interventions again, some of them will be really common lifestyle interventions. Diet. We're actually looking at an intervention right now that is a psychological intervention that increases positive affect. So positive mood. Does increasing positive mood change the rates of aging, and I hypothesize, yes. I think it's gonna do that through making it more likely that people adopt better health behaviors. I would hypothesize it probably has some direct effect, that mood itself may affect our biology and certainly vice versa. And so, that would be another example. And then looking at repurposing medications that are used, you know, for other things. So an example might be metformin has been out there a lot in the news, right? This is a medication used to treat diabetes and in some insulin resistance. Does that have an effect directly on biologic aging. These GLP-1 agonists, right? Medicines like Ozempic or Weygovy, you know, medications that have effect upon appetite, caloric intake, lead to weight loss. How do they affect, again, indices of aging? But I do wanna say like, we're really interested, and I would say our sort of overarching objective is to really generate a body of high quality, rigorous science to help us understand, again, the effects of these different interventions on aging. Not simply, looking at a biologic mechanism to say, oh, it makes sense that this drug should work. No, we need to test this in humans safely, and get objective evidence of efficacy or not of these different interventions on aging or age related outcomes. 

[00:17:07] Erin Spain, MS: And this could end up being a global initiative actually with potential partnerships that you're already trying to form around the world. Tell me about this idea that the Human Longevity Laboratory could go global. 

[00:17:19] John Wilkins, MD: Yeah. That's one of the really exciting, potential directions we'd love to go. So, you know, right now we're looking at creating other longevity labs across the U.S. Particularly if you start doing things like clinical trials, it really is important to have multi-centered clinical trials, for multiple reasons. But it's important to bring participants who are living in different parts of the country to make sure you have really a diversity. Let's say you have a positive finding, like is it really generalizable or was there something particular about the group of people you studied at, let's say Northwestern and Chicago, that's just different than the rest of the country. And I think that same concept carries over to other countries. And so I do think as we start to really branch out, and again, understand different interventions and how they may affect rates of aging, we really need to have multi-nation, interventional kind of studies and a network of longevity labs around the world could really help us do that. As I'm sure you can imagine, there's sort of different cultural norms, different environmental exposures for folks living in different parts of the world that could definitely affect aging and could affect the efficacy and or effectiveness of any of the potential interventions that we might use. It also can bring up some really fascinating issues we have to culturally tailor. Let's say it's a lifestyle intervention. Well, you're gonna have to do some tailoring, right, to the cultural environment in which you want to apply it. But yeah, again, to your initial question, yes, we would love to create this global network of longevity labs for doing both observational work and clinical trials eventually. 

[00:18:49] Erin Spain, MS: So as we wrap up today, for people listening who maybe they wanna know just from your expertise, what are three things that people could do starting today to possibly extend their biological age? 

[00:19:02] John Wilkins, MD: I would encourage everybody to go to the American Heart Association and look up Life's Essential Eight. Life's Essential eight are eight modifiable determinants of cardiovascular health. And it turns out, by the way, that optimizing your cardiovascular health also reduces your risks for many other chronic diseases. So number one, optimizing body weight to the best of one's ability or at least making improvements in lean body mass. Number two, eating a heart healthy diet. We typically recommend that sort of more of a Mediterranean eating pattern, although there's the DASH diet and if you go on the Heart Association website, you'll see all that. Regular physical activity. We typically recommend 150 minutes per week. Getting adequate sleep, seven to nine hours of uninterrupted sleep. Optimizing blood sugar. Not smoking. Moving tobacco smoke to zero. That certainly means zero cigarettes or cigars smoked, but also minimizing secondhand smoke exposure. Optimizing blood pressure. Extraordinarily strong predictor age-related disease in and of itself. And then one of my favorites, which is cholesterol. Making sure that your cholesterol levels are optimally controlled. I would say, you know, if someone wants to say, Hey, how can I optimize by biologic aging? I think we have the best evidence to really target those eight metabolic characteristics and health behaviors. 

[00:20:20] Erin Spain, MS: Well, that is some good advice to leave folks with today. And for folks who wanna possibly participate in this study, we'll put a link on our website where they can complete an interest form and perhaps they can be a part of it too. But I wanna thank you Dr. John Wilkins for coming on the show. This was really fascinating. It's an incredible topic and it sounds like really exciting work being done, and we will be following along as you make progress. 

[00:20:43] John Wilkins, MD: Well, you are very welcome and thanks for having me. It was really, really fun to talk to you. 

[00:20:46] Erin Spain, MS: Thanks for listening, and be sure to subscribe to this show on Apple Podcasts or wherever you listen to podcasts. And rate and review us also for medical professionals. This episode of Breakthroughs is available for CME Credit. Go to our website, feinberg northwestern edu, and search CME.