← The Peter Attia Drive
The Peter Attia Drive
#386 - Aging clocks—what they measure, how they work, and their clinical and real-world relevance
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Hey everyone. Welcome to the Drive Podcast. I'm your host, Peter Attia. This podcast, my website and my weekly newsletter all focus on the goal of translating the science of longevity into something accessible for everyone. Our goal is to provide the best content in health and wellness and we've established a great team of analysts to make this happen. It is extremely important, important to me to provide all of this content without relying on paid ads to do this. Our work is made entirely possible by our members and in return we offer exclusive member only content and benefits above and beyond what is available for free. If you want to take your knowledge of this space to the next level, it's our goal to ensure members get back much more than the price of a subscription. If you want to learn more about the benefits of our premium membership, head over to peterattiamd.com subscribe
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welcome to a special episode of the Drive. In this episode I take a different approach where I walk through a single topic in depth. And this is a topic that many of you have been asking about aging clocks. So in this episode I explain what aging clocks are and the difference between chronological age and biological age, along with the difference between those and something called the pace of aging, how epigenetic clocks work, and what they may actually be measuring. I'm going to talk about a randomized control trial that used three very simple interventions and tested four of the most common aging clocks. I'm going to also talk about another study that used brain imaging via MRI to study the pace of aging and see what could be gleaned about not just the risk of dementia, but also mortality. I'll discuss the biggest limitation in the field, which is whether changing a clock actually changes meaningful clinical outcomes. So without further delay, I hope you enjoy this special episode of the Drive. So if you wanted to run the perfect anti aging trial, you know, the end points would be really obvious. You know, you'd want to see fewer heart attacks, fewer cancers, fewer dementia diagnoses, and ultimately fewer deaths. So we would call these hard outcomes real outcomes that matter. These are the clinical outcomes that we all care about. Now, of course, the reason we don't see these trials is that they would take a very long time. These would literally be 20 year trials and with that would come enormous complexity and cost. Furthermore, it would be very difficult to ensure that whatever intervention you put in place was being put in place for the duration of this time. I mean, that would be not that hard to do if it was a drug trial, because it's relatively easy to take a drug. But it would be more challenging for a lifestyle trauma. Okay. So every few years, the fields of geoscience and medicine and cardiovascular disease, et cetera, they go looking for a proxy or a shortcut. So some intermediate marker that could move faster than these hard outcomes, but that would still predict the hard outcome reliably. And I think over the past few years, what we've really seen is that aging clocks are the most interesting and popular proposed shortcut. Again, I don't use the word shortcut with a. With a sort of negative connotation. It's like, this is what we need. We do need a shortcut. We need. We need a proxy. So, again, the idea here is pretty compelling, right? Imagine you could have a single number that would predict your actual aging or your, your actual biological age that's different from your chronological age, or maybe a rate of aging that reflects a new trajectory you're on. This could be very valuable in designing clinical trials or looking at interventions and even at the individual level, understanding if you've made a change and is it making a difference. So this would, you know, think about this as a foray into precision medicine. Now, there's a little bit of a problem in my mind because these aging clocks are being marketed as the latest and maybe best way to keep tabs on your health. Lots of people are ordering them. They're available to anybody. They're sold by longevity docs who promise to improve your biologic age with groundbreaking, you know, combinations of peptides or other elixirs. But I think it's worth looking into these a little more closely to understand what the science can actually tell us. And I think the best way to do this is to look closely at two studies, two very interesting studies that can help us get at the fundamental questions that we really want to be asking around this, which is what is the clinical utility of an aging clock? So before we do that, though, I just want to kind of make sure everybody's starting from the same. The same footing in terms of understanding the biological stuff that we're talking about. So what is an aging clock? Well, basically, at its core, it's a prediction model. But let's take a step back. Your chronological age is also a prediction model. You see, if I told you that in front of me There is a 20 year old and there is a 70 year old, and I asked you to predict which one of those people is going to die first, I think everybody would, knowing nothing else, make the correct prediction. Now, we could layer onto that certain other factors. So if I said, okay, Well, I actually now have two 70 year olds in front of me and one of them has cancer and the other one does not. Do you predict which one of those is going to live longer than the other? And again, without knowing anything beyond what
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I told you, I think everybody would
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make the same prediction. And so this idea of using information to predict mortality is not new. It is the entire basis of, of the actuarial underwriting industry. And there are companies that are exceptionally good at doing this. These are called life insurance companies. And their data are incredibly proprietary and it's really less so their data and more so what they do with the data that is incredibly proprietary. Right. They, they gather a lot of information about you. They, they do a blood draw on you, they know your age, they know various factors about you, they take your blood pressure, your weight and things like that, relatively rudimentary stuff. But from that they have these tables, again, highly proprietary, that seem to do a very good job of predicting when you're going to die. And so the question is, would one of these aging clocks be even better? Okay, so let's talk about how these things work. So they typically work by starting with some biological data. And the most common thing that we're going to hear about is epigenetic data. So this is DNA methylation. And then they train an algorithm to look at that and predict something age related. So I think it's worth spending a minute on DNA methylation. I don't want to go far down the rabbit hole on this, but you, you've undoubtedly heard the term, and so I just want to make sure everybody's playing from the same level. So DNA methylation is a way that we, or the way that the body modifies epigenetically what the DNA expression is. So it doesn't change the sequence of DNA, but it can influence how the genes are turned on or turned off. Right. So that's what we call expression of genes. So when you modify the epigenome, which is basically when you put a methyl group, so that's a carbon with three hydrogens, when you put it on the backbone of the DNA, that impacts whether or not that section of DNA gets turned into rna. That's what we mean by expression. You may have heard the term cpg, but not in reference to consumer packaged goods. But a CPG refers to the location where these methylations most commonly take place. If you remember back to high school biology, we have these four nucleotides, the C is the abbreviation for cytosine. And so where these things typically occur is right on the phosphate bond that links the C, the cytosine with the G, the guanine nucleotide. So when we talk about CPGs, that's just kind of another way that people kind of quickly talk about the methylations. So the methylations that occur at these cpg sites will then affect quite strongly the genes that are near to those areas. And why we care about this, of course, why I'm even talking about this is these methylation levels of many sites actually change somewhat predictably as we age. So this is kind of the rationale for all of this, right? Is as we age, methylation sites change. Ergo, if we can measure what's happening at methylation sites, can we impute age? Can we impute something better than chronologic age? Because remember, chronological age is an awesome predictor as it stands. But we're asking, can we do better? Because chronologic age is great at telling you that on average a 60 year old is going to live, you know, a shorter duration than a 50 year old. But we know that that's not true at the individual level. There are plenty of 50 year olds that are gonna have a shorter remaining life than plenty of 60 year olds. Just depends on the individual health and a whole bunch of other things. So we wanna get at that difference. Okay? So these patterns are gonna shift gradually over time and various factors, behavioral factors such as smoking, metabolic health, inflammation, actually play a role in that. And so for this reason, researchers came to the conclusion, you know, roughly 10 little over 10 years ago, that we could use these as kind of a molecular record keeping of what's going on in the body. And I think that's probably why DNA methylation has created such an important and foundational part of, of the clock story. So that's why I kind of went a little deep in the weeds there. I think it's important. So, you know, you've probably heard of the Horvath clock, that's, that's one of the earliest first generation clocks. And that was obviously based on this. So these models were trained on large data sets of DNA methylation, which were measured and collected from thousands of individuals across a wide age range. And they're mostly using cross sectional cohorts rather than tracking an individual over time. Why? Because as exciting as it would be to track an individual over time, those data sets are somewhat limited and they're harder to get. Whereas if you take very large cohorts where you just slice the population, you would get access to 20 year olds, 25 year olds, 30 year olds, 50 year olds, 60 year olds, 70 year olds, 90 year olds, et cetera. And the hope would be that, hey, we're going to see what the signature of methylation is, you know, over time. So given that chronological age was the outcome that the model was trying to predict, it's not really surprising that these clocks became very good at estimating age, often within kind of a few years of age. But at the same time, the fact that patterns of DNA methylation change consistently across ages of individuals, that had a biological interest to it. And it suggested that there might be certain areas in the genome where methylation shifts occur in a predictable way as people get older. Okay, so from a clinical standpoint, what does that tell us? Well, estimating chronological age, which is what these first generation clocks did, wasn't adding any value because we already know chronological age. So it was more of a proof of concept. But that's when the researchers realized, okay, what we really want to do is come up with something that could be better than chronological age. And that's where this idea of biological age could come from. And I just want to explain, like sort of an extreme example of what this would look like. So again, let's say you took two 60 year olds who, I didn't tell you anything else about them other than they're both 60 and they're, let's just say they're both the same sex. So two 60 year old women. So an actuarial table would say, based on their chronological age, these women both would have a life expectancy of, I'm making this up, 27 years. So if you're 60, your life expectancy is 27 years, you're expected to live to 87. But if we could look at the methylation of these two women, and one of them came back and we were told, yes, but her biologic age is 65 and the other one's biologic age is 55. The question is, does that delta of 10 years between them actually translate to 10 years difference in lifespan? And so that's what these next generation of clocks set out to do. Instead of predicting age, they started training on more clinically meaningful outcomes. So they were trained on, you know, physiological biomarkers, data sets that would be able to track mortality and basically even things like rate of physiologic decline or pace of aging. So the last category, this pace of aging one I think is particularly interesting because it aligns with what most people think they're getting when they look at a biologic clock, which is not just how old am I, but how quickly am I aging right now? This topic came up, by the way, in a podcast with Rich Miller, which was when they went back and looked at data from the various ITP winners. So recall, Rich Miller is the guy who oversees one of the parts of the interventions testing program at the University of Michigan where they take drugs like rapamycin, metformin, nicotinamide, riboside, et cetera, they put them into mice over the duration of their life, and then they look to see which of these drugs extend life. Well, they took all of the ITP winners, plus other things that were known to improve lifespan of mice, such as caloric restriction. And they identified roughly a dozen or so not epigenetic changes, but actual things that showed up, proteins that showed up in those animals, something we would refer to as the proteome. And they were able to generate in those mice predictive age rate calculators. So, again, a little too soon to tell if that's going to pan out in humans, but very interesting. So many of these second generation clocks were designed to predict outcomes like mortality by incorporating methylation patterns that correlated with things like smoking exposure, inflammation, and things like that. And while that's useful, it's important to understand that that kind of changes how we interpret the output. So if a clock is particularly capturing a biological fingerprint of something like smoking history or cardiometabolic health, then a shift in that clock might reflect an improvement in that pathway, but it might reflect something really uninteresting, like you're just recovering from a cold, or you have lingering inflammation from a heavy workout. So this is kind of where the excitement around aging clocks collides with the reality of measurements. Because there's basically two types of noise you have to consider when you look at these clocks. You have to consider biological noise, which is the example I just gave of how do I know that what you did in the day or week before didn't transiently impact what I'm measuring, but truly has no impact on your health versus the measurement noise, which is how hard is it to actually measure these things? So even in a very high quality lab, DNA methylation measurements are not very stable. So variations can arise from a lot of things that how the sample is handled and stored, differences in the methods for DNA extraction, you know, the efficiency of the conversion steps that are used to read the methylation patterns, the batch effects on methylation arrays themselves, and even differences in the mixture of immune cells present in the blood at the time that the blood is drawn. Because Remember, these are all being done not on tissue, but on cells in the blood. And then on top of that, you know, the clocks are typically measuring hundreds of thousands of methylation sites across the genome and then trying to collapse all of that information into a single summary score. And again, we love when we can do that, when we can convert lots of data into a number. But we have to understand that we run risks of doing that. So again, I'm not saying any of these things aren't challenges that maybe couldn't be overcome, but I just want to make sure everybody understands, like how, how technically complicated this is. So again, just keep in mind biological noise and then technical or measurement noise. So basically, I think the reason these clocks are exciting is that they're kind of offering three things that people want. So the first one I just kind of alluded to, which is compression. So aging is very multidimensional. There are so many things that are going on. Your immune system is declining, your fuel partitioning skills are declining, vascular health is declining, brain function is all these things are declining as we age, on average. But the clocks are attempting to take this and compress it into a single number. On the one hand, that's exciting. We love when we can do things like that. BMI is a great example. Again, it's only combining height and weight, but it's turning it into a single number. But we have to be mindful of the fact that the more you compress something complicated, and BMI is a great example, it's only taking height and weight and compressing it into a single number and trying to be a proxy for muscle mass, body fat, and things of those nature. And here's the thing, on average, it's pretty good, right? At the population level, BMI is pretty good. If I told you that in one city the bmi average was 24, and in the other city the BMI average was 29, and I said, tell me which of those two cities do you think is healthier? Again, knowing nothing else, you're all going to say 24. And you're almost assuredly right. But if I told you I have an individual who's got a BMI of 24, and I have an individual whose BMI is 29, tell me which one's healthier. Truth of the matter is, it's going to be tough. There are some really unhealthy people with normal BMIs, and there are some really healthy people, usually quite muscular, that have quite high BMIs. So this idea sort of falls apart. And you can imagine how much more susceptible we would be to that when we are taking a much larger and more multidimensional problem. Okay. The second big thing we want out of clocks is not just compression, but it's speed. I kind of alluded to this at the outset, right? It would be amazing if we could do clinical trials for a year and get the type of benefits in terms of insight that we would get if we were doing these clinical trials for 20 years. The third one I also kind of alluded to already, which is at the individual level, we want feedback. I want to know that if I changed my diet from this to that after three months or six months, was that the right change to make? I want to know that if I'm taking this supplement which supposedly reduces inflammation and supposedly does several other factors that are targeting hallmarks of aging, I want to know if it's doing it. So bottom line is this is why we want em. Question is, does it work? Okay, so the best way we could think to talk about this is internally, meaning our research team, we looked at a couple of studies that we thought really highlighted a couple of the important points here. And so that's what I want to talk about. Here are these two studies. Okay, so the first study looked at an intervention that was a very simple intervention. They used omega 3 supplementation, vitamin D supplementation, and exercise. And then they asked the question, will those simple interventions, and I'll talk about them in a little bit more detail, move the needle on the four most common epigenetic aging clocks in a randomized fashion, randomized people to these things, measure clocks. Second study that we're going to talk about takes a different approach, but asks if we can estimate a person's aging, pace of aging using structural features from a single brain mri. So different approach, but let's talk about them both. Okay, so let's start with the first study. This was referred to as the DO Health study. And it's, I think it's a reasonable use case example. Okay, so again, if an aging clock is going to be useful, the best case scenario is probably that it can detect biological signals in a randomized controlled trial. So if you think back to, again, the problem we started with, the endpoint you really care about is something like mortality or incidence of disease, like dementia or cardiovascular disease or cancer. And the interventions in this trial, which are, you know, very reasonable things to propose, you're not going to figure out in a year, two years, or three years if they're having an impact on those things. But if you have a Biological clock that is true to those things. You're gonna be in the, in the end zone. So what did the study do? So the study took, you know, it was a, it was a European large study. It was a two by two by two factorial. So that means they tested these three interventions that I talked about. So giving vitamin D, giving epa, DHA and assigning exercise. Um, they tested them individually and in combination. So each individual was then randomized to one of eight groups for the duration of the study, which is a three year duration study. The measurements were collected at baseline and then at three years. So you got a blood level at time zero and then at three years. So they looked at nearly 800 generally healthy older adults. So everyone was 70 plus, mean age 75, from Switzerland. About half of these individuals met the criteria for what we would call healthy aging. So they were basically free of chronic diseases, disabilities, cognitive impairment, any other limitations, and they were quite active. About 88% of these people reported regular physical activity. And about 60% of these people reported exercising more than three days per week prior to enrollment. Okay, so again, the interventions, 2000iu of vitamin D, a relatively modest amount of EPA and DHA. So one gram a day that contained 330 milligrams of EPA, 660 milligrams of DHA, and this was from marine algae. And then adherence for both the vitamin D and Omega 3 levels was assessed by changes in serum level. So they did have the ability to kind of go up or down based on what they were measuring. And then on the activity front, they had a simple home based exercise regimen that consisted of Mostly strength training, 30 minutes, three times a week. And this was added on top of whatever you were doing at baseline. So whatever you're doing at baseline, fine. But we add this and then compliance was tracked with exercise diaries and follow ups. So my first thought when I looked at this was these are kind of modest interventions. You know, a gram of Omega 3 is pretty low. 2000iu of vitamin D is not going to do much. And 90 minutes of exercise in people who are mostly already exercising. You know, I guess it depends on what they're already doing, but truthfully, I would have thought that was the most interesting thing. But none of these are herculean things, especially when you combine it with the fact that most of these participants were relatively healthy and physically active. So it's not clear what you would, what you would see here. But that said, I think this trial was designed well, and it's a useful way to test Whether these aging clocks can detect subtle changes over time. So let's talk about the tests. Right? So again, time zero and time three years they measured DNA methylation and then they applied these clocks. So let's talk about the clocks that they use because I mentioned that they used four next gen clocks. So the first one is called phenoage. So this test uses methylation data from about 500 CPG sites and it's trained to reproduce clinical biomarker score that predicts mortality risk. That biomarker score then incorporate takes measurements beyond just the CPGs. It looks like it looks at albumin, glucose, C reactive protein, kidney function, white blood cell count. And then the clock reflects the physiologic health rather than just sort of their chronological aid. The next one is called Grimage. This uses methylation data from about a thousand cpg sites to estimate the level of plasma proteins that are linked to aging such as GDF15, leptin, PAI1 and also smoking exposure. So these methylation derived biomarkers are then combined with bio, sorry, chronological age and sex to predict a time to death. So this is kind of an interesting one, right? This is that one that would, would try to get at what I was saying earlier, which is if you have a 60 year old, the actuarial time to death expectation might be, you know, I'd made an up a number but say 35 or 37 years, if the, if you did a grim age on that person and it said 20 years, that would suggest you that this person is much less healthy than the average 60 year old. And if it said no, 40 years, you would say, oh, this person's healthier than the average person that you would expect to see that age. Okay, then there's another one called grimage2 which is the same as Grimage. It just has an updated set of biomarkers. So it's using C reactive protein and A1C along with some other refinements. And then you have another one called the Dunedin pace estimate, which is really trying to estimate the rate of aging rather than biological age. So this uses the methylation patterns of 173 CPG sites. So unlike the others which were trained on cross sectional areas, this is trained on a longitudinal set of data across a population in New Zealand called Dunedin. And that's what allowed them to track over time what the changes were and try to estimate this if you will, first derivative. Okay, so we'll put in the show notes a table that just kind of links to all of that so that you, you can sort of keep that in mind and keep coming back to it. So just to summarize that the first three, right, which were the Feno age, the Grim age, the Grimm age too, those are ones that are kind of looking at biological age and trying to see if that can be more predictive than chronological age. And then the Dunedin pace is designed to estimate the pace of aging. Okay, so again, important distinction. And again, what does it matter, right? The biological age might tell you that a person's physiology resembles that of a typical person who's older or younger. That was the example I gave. The pace of aging is trying to answer a slightly different question, which is, at the time of my measurement, how fast is the system deteriorating? Okay, so let's talk about what the study found. We'll link to the figures in the show notes so you can go and actually see the figures yourself, because I think the figures sort of tell a thousand words, right? But basically they looked at what each of the four tests showed, and they have forest plots for each of them. And they look at each of the four different forest plots for each of the interventions, combinations of and thereabouts. So what I'll just call out is what was significant. So the Pheno age study found significance, an effect size of.02 for just the omega 3 intervention, and then for the omega 3 and the vitamin D intervention for omega 3 and exercise, and then for all treatments combined. When you looked at the Grimm age by itself, just this first gen Grim age, it found no significance, no change across the board in anything. When you looked at grim age 2, the only thing that showed significance was omega 3 versus placebo. And when you looked at the Dunedin pace, the only thing that showed significance was omega 3 versus placebo. So the bottom line here is, on balance, you know, the most consistent finding was that something about omega 3 supplementation moved the needle in at least three of the four clocks. So the only clock that it didn't move the needle in was the first gen Grim age clock. Now, that said, Even though the Omega 3 change showed consistency in three of the four tests, the magnitude of the effect was quite small. So if you translate it into something a little more intuitive, the effect corresponded to about three months of reduced aging over three years, depending on which clock you. You look at. And again, I still actually think that's a larger magnitude than I would affect. But maybe if you believe these clocks, the translation is, for people with really, really low omega 3 intake, you don't need much to move the needle. The vitamin D supplementation as I said didn't really impact the clocks at all. But again, the, given the dosage, I don't think that was surprising. 30% of these participants at a baseline level below 20 nanograms per deciliter. So it's possible that just the 2000 IU wasn't enough to get them anywhere. And then exercise also failed to show an independent effect. Again, I think context here matters. Remember, these participants were already physically active at baseline. So it might be that for a study of this size and this duration, you weren't going to see the effect unless you did it in people who were not active. So again, not sure what to make of this. I think that the results of this study, you know, don't answer a ton of questions. The, these interventions are quite common. Not sure if they were dosed correctly. I don't recall actually, now that I think about it, what they pre selected as their power analysis. In other words, to pick the sample size that they picked, they had to assume a certain effect size. And it might be that the effect size was, it was a real one, but it was smaller. That would mean it might not be clinically significant. But I suppose that the use case here is reasonable, right? Which is were there small molecular shifts over time in a, in an otherwise well controlled setting. Of course it also begs the question though, which of these clocks do you believe? Right, because if you think that Grim Age is the right clock, then it would say none of these things mattered. If you pick fenoage, you would say, gosh, everything mattered except for exercise. And if you pick Grim Age 2, you would say Omega 3 was the only thing that mattered. And the same with Dunedin Pace. So I still, at least on a personal level, don't know that I can tell which of these clocks makes the most sense. Now one potential advantage of using an aging clock is that it does give a shared endpoint across different interventions. So if you at least believe that there's internal consistency, you could feel maybe more comfortable that okay, in an absolute sense, I don't know if these changes are right, but I'm, I could figure out that hey, I'm getting more bang for my buck doing more cardio versus more resistance training or vice versa.
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So the other thing I think that
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we don't know here is what the, what the measurement error was. So how much technical noise there was in these. We've talked about this earlier in the podcast, not this one, but previous episodes where, you know, there are lots of folks out there that'll go and buy the same, you know, Multiple versions of the same test, take a blood sample, ident, you know, single blood sample, and then spread it across multiple tests and you get different results. And so, you know, there are various reasons that that could be happening. It's not clear from this paper exactly what their technical spread was. But my guess is there's more noise in these measurements than say, measuring a blood glucose, where the assay is much easier and much more standardized lab to lab. You know, I still think that whether these clocks are actually capturing the biology we care about well enough is, I think that's an unresolved question. We, we can obviously ask different questions with clocks, but with most medical research we kind of focus on very specific outcomes. Right. We're going to look at muscle strength. If we're testing resistance training, we're gonna look at blood pressure. If you're looking at an antihypertensive drug or LDL cholesterol, if you're using a lipid lowering drug. I like what the aging clocks are trying to do because not all things are gonna be measured in single parameters. And even if you do lower LDL by itself, it would be nice to know how much of an impact is that having on my overall aging. So I think maybe the most important thing here is that if an aging clock could allow a researcher to ask a long term question within a shorter trial, that alone to me is reason enough to do this. And then everything else, whether we individually can use them, those would be fantastic. I think what I liked about this paper was that the authors didn't kind of use just a single clock that gave them the answer they were hoping for. They pre specified four clocks. They showed the data for four clocks. We talked about the results.
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Right.
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Three of the four showed a benefit for Omega 3. Again, is that because they're detecting using different CPG sites? Is it because they're using different biomarkers? It's not, it's not, it's not clear. The authors point out that this type of discordance is not unfamiliar. There's a very famous study called the calorie trial. This was run out of Pennington many years ago. Eric Robinson, who's a previous guest on the podcast, actually was the PI for that. But the data set from calorie has been used multiple times. This was a calorie restriction study and it showed that. So the calorie restriction showed a reduction in pace of aging using the Dunedin pace clock, but it didn't affect the Feno age or grim age, which were the these other first generation clocks. So again, this is not. This is not unusual. So where does this leave us? The first study, the DO Health trial, shows that aging clocks can detect small biological changes in response to an intervention. And in this case, it was Omega 3 supplementation that appeared to slightly slow several epigenetic clocks over three years. The second study, the Dunedin PAC NI paper, showed that scientists could build new types of aging clocks, in this case using structural brain imaging that appear to capture meaningful patterns related to cognitive decline, frailty, and even overall mortality. So, taken together, these studies illustrate both the promise and limitations of aging clocks. On the promising side, these clocks may help researchers detect early biological signals in situations where traditional clinical outcomes would take decades to measure. And I think that's incredibly valuable for aging research. Running a 20 year prevention trial for every possible intervention, you know, simply isn't feasible. And the biomarkers that capture aspects of the aging process could help us prioritize which ideas are worth testing more rigorously and putting more resources into. But at the same time, these clocks are still models. And models come with limitations. In fact, to quote a famous physicist, and it's debated if it was Fermi who said this, all models are wrong. Some are useful, but the question is, how useful are these models? Well, different clocks capture different aspects of biology. Small shifts in the measurements don't necessarily translate into meaningful improvements in health outcomes. And most importantly, we still don't know whether changing the clock actually changes what we ultimately care about. Things like disease risk, disability, or lifespan. This uncertainty matters a lot when we move from research into consumer health. Right now, aging clocks are increasingly being marketed as a tool for individuals, something you can order online, track over time, and use to evaluate your own lifestyle changes. Some of these companies even promise to improve your biological age with supplements that they will conveniently sell to you as well. But based on the current evidence, it's not clear that these numbers actually give consumers any actionable information. If your aging clock changes by a few months, what should you do differently? Should you change your diet? Your exercise program? Your medications? Take more of the supplements? At this moment, the science as it stands, does not provide clear answers to those questions. And in many cases, we already have much more reliable metrics that tell us about health and longevity risk. Things like blood pressure, glucose, lipids, whether you're smoking or not. All the various metrics we have around physical fitness and body composition. These are not particularly glamorous biomarkers, but they have something that aging clocks don't have yet. Decades of evidence linking them directly to real clinical outcomes. In Fact, if you take a step back for a moment, we've already solved a large part of the problem that aging climate clocks are trying to address. There's a particular industry out there that is so good at doing this that their formulas are proprietary. Life insurance companies have been predicting mortality risk for decades using actuarial models based on these various factors. In fact, I recently reached out to a senior member of a life insurance company and this person shared with me that if they ever see a deviation in expected premium payouts that exceed 1%, it would be considered the most unusual event they could imagine. So that means that at the population level, they have to be able to predict mortality at a degree of accuracy that exceeds anything we can imagine. And I further asked if they were using any of the commercially available or research grade biological clocks, and the answer was no. So I think that tells you something that these companies are still doing their jobs surprisingly well and they don't use any of the aging or biological clocks. They rely instead on the data that we understand. So at least for me, I think about this as if someone were to offer a biological age score. It's worth asking them what that number is actually telling them. Is it telling them something new? Or at best, is it just repackaging information you already have or understand? So again, this is not to say that these clocks provide no value. They are fascinating scientifically, and they may become more valuable as research tools over time. They may evolve into clinically meaningful biomarkers over time, but right now I would say they would be best viewed as experimental tools for studying aging, at least at a broad enough population level, but not as definitive health metrics for individual decision making. If you're interested in your own longevity, the takeaway is quite simple. Instead of obsessing over whether your biological age is 42 or 45, it's probably much more productive to focus on the things you already know are going to matter, right? Staying active, eating a balanced diet, getting appropriate sleep, maintaining and measuring clinically validated biomarkers. Now, again, they might not sound as flashy as biological age and the scores that are attached to them, but they remain some of the most powerful tools that we have for improving both lifespan and healthspan. And as aging research continues to evolve, perhaps one day these biomarkers that we get out of these clocks will help guide those efforts even further. But I think for now, it's safe to say that the fundamentals still matter most.
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Thank you for listening to this week's episode of the Drive. Head over to Peteratti md.com forward/show notes if you want to dig deeper into this episode, you can also find me on YouTube, Instagram and Twitter, all with the handle Peter Atiamd. You can also leave us review on Apple Podcasts or whatever podcast player you use. This podcast is for general informational purposes only and does not constitute the practice of medicine, nursing or other professional healthcare services, including the giving of medical advice advice. No doctor patient relationship is formed. The use of this information and the materials linked to this podcast is at the user's own risk. The content on this podcast is not intended to be a substitute for professional medical advice, diagnosis or treatment. Users should not disregard or delay in obtaining medical advice from any medical condition they have, and they should seek the assistance of their healthcare professionals for any such conditions. Finally, I take all conflicts of interest very seriously. For all of my disclosures and the companies I invest in or advise, please visit peterattiamd. Com about where I keep an up to date and active list of all disclosures.