Chrononutrition And Biological Aging

Your body keeps time, and your fork might be one of the strongest signals it listens to. We get into chrononutrition, the growing science of meal timing, and why aligning breakfast and dinner with circadian biology may change far more than your waistline. Using a new large-cohort analysis from NHANES, we talk through how first meal time, last meal time, and the length of your daily eating window correlate with biological aging models, including organ-specific aging patterns in the heart, liver, and kidneys.

We also make the research practical. We share why late dinners and long grazing-style eating windows can push you toward insulin resistance, weight gain, and worse sleep, and why shutting down food earlier in the evening often becomes the “linchpin” habit that makes everything else easier. Then we zoom in on breakfast strategy, including why a high-protein, higher-fat morning meal can improve satiety, muscle protein synthesis, thermogenesis, and energy through the day, plus examples of simple high-protein breakfasts you can actually repeat.

Finally, we explain biological age testing in plain language. We compare epigenetic clocks based on DNA methylation with functional blood-based models like KDM and PhenoAge, and why trending these markers can motivate real behavior change. If you care about healthy aging, metabolic health, time-restricted eating, better sleep, and a routine that works with your biology instead of against it, this conversation gives you a clear place to start. Subscribe, share this with someone you care about, and leave a review with the meal-timing change you’re willing to try this week.

For video, slides and open source research articles: www.healthedgepodcast.com

Transcript

Welcome And Topic Setup

SPEAKER_00 0:00

Welcome to the Health Edge, translating the science of self-care. I am Dr. Mark Pettis with my friend and colleague, Dr. John Bagnulo. John, good morning, my friend.

SPEAKER_01 0:11

Good morning, Mark. Great to see you.

Chrononutrition Meets Circadian Biology

SPEAKER_00 0:14

As always. And uh we have another really fascinating topic, John, that reminds me, no, no matter how long you maybe have been um uh diving deep into various subject matters, whether it's nutrition science or fitness and human performance, uh there are always sort of new dimensions, new facets uh of these fields that continue to evolve. And one of the things that's certainly not a new topic per se, but I think is gaining a lot of traction in the clinical research and very much aligned with circadian biology is the importance of meal timing, this concept of chrononutrition. How everything in our body, biologically, as we've talked about, is on a clock, and that clock is tightly and precisely synchronized with diurnal environmental conditions, sunrising, sunsetting, and different frequencies of light that we know are uh impactful in that context. And uh and so here we have a uh a study that we will look at, excuse me, that is pre-publication. Uh every now and then we review a paper that will be published. Um this is very recent data that will look at, this was accepted for publication a few months ago, that will look at the uh very important correlation of meal timing. How soon we eat breakfast, how late in the day are we eating dinner, and what is that window of consumption over the course of the day look like, you know, what we might call that eating window, and how all of those factors impact biologic aging. And while a lot of research has looked at the importance of meal timing for metabolic health, and we've talked a lot about that on the health edge, um, this um the outcomes that they measure here are biologic aging models, which are really very interesting and are, I think, are very much going to continue to be part of mainstream clinical research. And so this this paper looks at that and and the findings are powerful, right?

SPEAKER_01 2:46

Yeah, it's incredible. And again, it's that alignment that with so many facets of nutrition, lifestyle that that we discuss, you know, what I find there's a couple things I find really incredible about this. Number one, uh, which you and I have discussed online, the fact that every cell has its own clock is that that's incredible on its own. But then to think about you know, the hum early human experience, right? We always hunted and looked for food first thing in the first thing in the day, at first light, right? That had that was and is still in many areas of the world, that that's still the pattern of living, of daily living. And the the influences that that had on our biology still is still carried out today, right? And if we're not aligned with that early human experience where we're hunting, looking for food early in the day, eating food early in the day, and then you know, really shutting it down at the end of the day as the sun goes down, we're we're misaligned. And once we're misaligned and we have a lot of food and metabolic demands coming in with the food we're eating, the cells aren't geared up for that. The cells are just are not compatible with whether it's you know handling the glycemic load later in the day, you know, what we do with the protein we eat later in the day, it's not as efficient. I find those two things to be you know the most remarkable about about this story and that how that influences the biological aging that you know you know that you just mentioned. I I think the biological aging to a large extent is how aligned we are with this, you know, this early, early human experience that that controls so much of our physiology. So it's it's incredible, you know, a couple hundred thousand years later, you know, give or take, maybe give or take 10 or 20,000 years, depending on what anthropologist you talk to. But here we are, roughly 200,000 to you know, maybe more years later. And that early human way of life is still somewhat a requisite, right, for good biological aging.

SPEAKER_00 5:00

That appears pretty clear from the research, indeed. And so uh we'll I'm gonna pull up some slides here and we'll look at this study, what it showed. Uh, we'll then um do a brief detour, John, and just look at a few of the established techniques currently to measure biologic age. Uh, because again, I think more people um uh will be able to do this. You could take your own blood work and plug it into calculators, and uh many, many labs uh will probably start offering a biologic age result, excuse me, based on your blood work. And um, so we'll look at a few of those different models. Uh, we'll follow up with a few other recent studies that corroborate what this main study shows, and then we'll just bring it home as always with some practical information about how to apply this, John, not just in terms of timing of meals, um, but but I know you'll have some thoughts to share about how you might want to comprise the macronutrients uh of those meals, which is not something the studies that that we're looking at focused on. So we're trying to just integrate some recent themes with meal timing that I think can really give people the edge. And as we get into this stronger sun season, and I think many people are a bit more attuned, whether they're aware or not, of the of sunrising, sun setting, and how it impacts your experience of life and quality of life. Uh, this is a good time of year to be more mindful of all of this as you apply it, because you'll quickly realize dramatic improvements, uh, some of which intuitively wouldn't seem to connect to how early in the day you eat breakfast or what you're eating for breakfast at that time. Uh things like mood and cognition and um you know it their energy, uh, etc. So I'll pull this up. And I I like this uh term chrononutrition, John. It uh and again, more more papers are starting to reflect this sort of uh newer, if you will, concept. Um so in addition to what we eat, right, when we eat is very important. And so we're gonna be looking at this interconnection between meal timing, metabolic health, which is the driver really. Metabolic health is either your passport to aging and premature death and diminished quality of life, uh, or your uh biologic aging, uh, and and this metabolic health could be such that you're assuring yourself a longer life, an improved health span, or quality of life. And really, this is the holy grail. So this is really getting to the roots of so much of what disrupts or can enhance healthy human biology. And again, you just see how uh so many aspects of human health, from uh um the timing of eating during pregnancy, uh looking at cancer risks, certainly metabolic health, a lot of interest in autoimmune diseases like multiple sclerosis. And so these are um um concepts with wide implication for human health across the board. Anything you want to add to that, John?

SPEAKER_01 8:50

No, it's uh like you said, it you know, this this topic of chrononutrition or you know the timing that metabolism is is being activated and drawn on, it reaches into every every area of medicine, you know.

Study Design Using NHANES Data

Earlier Dinner Links To Younger Organs

SPEAKER_00 9:07

Absolutely. So here's a study that we are looking at here: dietary rhythms and biological aging across multiple organs. And uh again, this uh was accepted for publication just a few months ago and uh is waiting uh to be published. The group from China uh were the uh investigators here, and this is uh just a graphic looking at uh kind of a summary of the study, John. And basically they they took NHANES data. So, like so many studies today, they look at a large cohort. So this is thousands of of individuals in the NHANES data. These were adults, and of course, uh based on food frequency questionnaires, which we know do have some inherent drawbacks, uh, but this is the methodology that sort of the standard of care for so much of the nutritional epidemiology. Uh they looked at the first meal time. So, how soon after waking up uh did you consume your first meal, your breakfast? Uh they looked at last meal time. Uh what was the, you know, really how soon before bedtime did you consume that last meal? And what we're seeing today, John, I and I think this is part of the uh sort of computational um capacity, uh the sort of revolution of big data management analysis and AI, artificial intelligence, is when you've got a a uh uh a database, excuse me, as robust as NHANES, you can um interpret and look at various ways to interpret the data that often reveals patterns that the average human brain uh will not be able to see. And so they're able to fine-tune um algorithms based on these machine-based learning models that help them determine what are the best variables to predict biologic age, and they look at the correlation between chronologic age, uh, right, your date of birth and how old are you based on that, and biologic age, which for many will correlate with chronologic age, but but really the point of a lot of this research is to identify what might help people age more slowly. Uh and so uh these would be in individuals whose biologic age is less than their chronologic age. That would be considered a very healthy trajectory and a pretty good predictor of all-cause mortality, uh, cardiovascular, cancer mortality, metabolic health, quality of life, or is your biologic age older than your chronologic age? And that would suggest accelerated aging, and that would lead point to what are probably various metabolic health disruptors and things that uh one can do to change that trajectory. And then they the results here, which I I have a separate slide summarizing, because I realize anyone looking at this uh for the first time, it it's a kind of a busy slide. But the bottom line is that the last meal time earlier in the day, and and these are the two parts of the of the graphic here, John, that this is looking at, starting at 3 p.m. up until the upper uh limit of 7 p.m. was the best uh predictor, the best uh predictor of lower biologic aging, measured both as sort of total body, they looked at total body biologic aging, and then some of these techniques, as we'll look at in a moment, allow you to measure organ-specific biologic aging. And they looked at liver, they looked at kidneys, and they looked at heart. And across the board for organ and biologic aging, the earlier dinner hour was clearly a better uh match, a better alignment uh with biologic age.

SPEAKER_01 13:56

Um after nine, and after 9 p.m., that's when you're in the danger zone here.

Why Late Eating Drives Weight Gain

SPEAKER_00 14:00

That's when you're in the danger zone. And uh, of course, a lot of people eat very late in the day and often right up until bedtime. Um and uh again, that first meal uh generally within uh two hours of waking up seemed to be the best predictor of slower biologic aging across the board as compared to having that first meal after noon. So somebody goes to bed at 1 a.m., they wake up at 9 a.m., they don't really get around to eating until afternoon. That late-day first meal, that close to bedtime late day last meal are major disruptors of biologic age. And that's that's essentially what they were looking at here. And again, unlike meta, we know that this sort of correlates with metabolic health, obesity, um, high blood sugars, pre-diabetes, diabetes, hypertension, high triglycerides, right?

SPEAKER_01 15:09

Just weight gain, weight gain in general, Mark, right? I mean, we could take this conversation, you know, outside of the biological aging topic, just for our listeners' sake, and we could say, hey, this is the number one reason in the past, so many college students had such significant weight gain in their first semester, their first year of college, right? You know, you're out of that high school kind of way of life, that pattern where you get up early in the morning, go to school, and you eat eat at least something, you're active, and then you get to college. And I, you know, I think a lot of people think about that freshman 15 or whatever number you want to assign to it, and they tend to think more about the what students are eating. I always ask, you know, student athletes, I always ask them to reconsider the when they're eating. And like you're saying here, right? A lot of those, you know, first year college students, they're up much, much later than they would have been uh in high school. You know, they're up, like you're saying, one or two a.m., not eating until noon or later. And I think that's more responsible for that weight gain and all the changes that we see in college students. So, I mean, again, I don't mean to digress here, but just for our listeners' sake, we're not just talking about biological aging, which this paper does a remarkable job of uh identifying and really you know showing the effects, but we could this spills out into just really much, much broader effects on human health.

SPEAKER_00 16:36

Definitely. And um, there's a robust uh research base when you look at uh night shift workers, um healthcare first responders, um, much higher prevalence across the board, we know of weight challenges, insulin resistance, inflammation, depression. Uh, and so um um I think that is a a good example of where this biologic aging data um uh if there's any value or utility, it does seem to be a good predictor of the burden of chronic complex health disease challenges that people confront and very much um predicts health span challenges. And as always, John, what we love about these topics is they always come out the other end with very discrete lifestyle behavioral changes that one can consider that can realign these clocks. And so um the right this mismatch between these biologic clocks in each cell in our body, all 30 trillion cells, uh, and the extent to which modern life uh uh confronts us with options that are no longer aligned or compatible with the the memories that our bodies hold, that our cells hold, of what uh uh circadian timing should look like. And and so uh there's so much validity. Um, and I and I think the biologic age markers as they gain traction and popularity in the research are going to become important predictors of the future. And and that can be very helpful and motivating for people who might be struggling with with behavior change. So um I'll bring these slides back up, John.

SPEAKER_01 18:42

Yeah, and I think that again, to just with that last slide, you know, I I think for some of us that last meal the day at three o'clock in the afternoon, that's tough, right? I mean, especially, you know, I have a young family, so I'd have to pretty much uh for me to have something like that would be would be really tough, but I don't think you have to ruin good for best. I mean, I think that's the take-home message here because whether it's three o'clock or it's five o'clock, those are, you know, again, with a family and wanting to have that meal and thinking about the social value of it. Exactly. You know, you gotta wake some of those, um, some of those cost benefit ratios with this. But what's really clear and what this uh what this corroborates is that you know, anytime you're after eating after 7, 730, you know, it's a downward spiral from there in terms of human physiology. So if you can eat at five, great. Um, but I think this is just further evidence that you really got to shut down the kind of the feeding window at around 7 or 7:30. Otherwise, you know, you get into that uh you know, metabolic, it's really promoting metabolic syndrome for just about everybody. Exactly.

SPEAKER_00 19:58

And it's such a great point, John. Uh, like in any um clinical study, any um recommendation for a lifestyle change, one has to always best adapt to to their unique circumstances. And it's so funny, John. Uh excuse me. Yeah, I'm about to turn 70. My wife is a few years older than me. And uh uh it's easy when you're young to kind of tease older adults and how early they eat.

SPEAKER_01 20:33

Yeah, and how early they shut it down.

High Protein Breakfast Strategy

SPEAKER_00 20:35

Right, yeah, play special, uh excuse me, that senior discount, right, at 4 p.m. Um, as I've of course, our kids are grown, and to your to your point, uh, we're up much earlier, we go to bed much earlier. So the two of us are, you know, 5 p.m. supper time. Uh and uh a little bit earlier on occasion, we'll have an earlier meal. And it's been easier to adapt that to this sort of chapter in our lives than it would have been when our kids were young. Um, but it was still within that window. Even when we had young kids, we we tended to eat before seven o'clock. And uh while these studies look at adults, I think it's important to consider the fact that, you know, when kids are eating at all hours of the evening and night, uh, you know, it's definitely going to disrupt their sleep. They probably aren't gonna perform as well in school. Uh and uh so these are obviously uh relatable to anyone across the age continuum. But this is the basic uh conclusions that we just looked at here, John. Eating breakfast earlier in the AM after awakening was clearly associated with metabolic benefits. And there are some macronutrient considerations, though these studies again didn't look at that. They just looked at meal timing, not meal quality. I know you're very interested, John, in the research that would suggest that not only is an earlier breakfast important, but what we consume at that meal has huge implications for muscle protein synthesis, insulin and glucose management, satiety. Recently we talked about thermogenesis. And so I just want to pause here for a second to have you talk a little bit about what an ideal breakfast might look like.

SPEAKER_01 22:43

Yeah, no, it's definitely the greatest return on the whatever protein you eat during a day for whatever reason, whether that's for basic repair processes, uh, an effort to gain lean body mass, or to have a better kind of like more fat-burning metabolism, you're going to get the greatest response in all of those areas with a high protein, high-fat breakfast. Because that thermogenesis, that heat that is produced when your body metabolizes protein, uh, it carries over the rest of the day, kind of raises your body's uh your body's thermostat, let's say, for the day. So you're gonna burn a little hotter. Um, you know, and you're you're gonna burn more calories, you're gonna be just more metabolically active, you're gonna be more insulin sensitive, you're gonna get greater um muscle protein synthesis, as you already said, for every gram of protein that you consume in the morning, um, it's it's much more efficiently used, right? You're gonna get, you know, an X factor of somewhere around like 0.8. So you're gonna get 80% of that protein is gonna help you restore or build muscle as opposed to it might being under 50% when it's eaten later in the day. So you're just getting a much, much greater window of potential for favorable influence on your metabolism and your body composition with that high protein, high-fat breakfast, because you're making your body prefer a fat-burning metabolism the rest of the day. You're building more muscle in that early part of the day. And again, it's just it's amazing, Mark, because I look at this on the cellular level, but I also the ancestral component to this is just remarkable because that's how humans ate. And that's, you know, that's where we got the majority of our nutrients, our energy over the course of human history. And this last few hundred years is just an aberration from that. And really, the clock, the clock that we all carried, it hasn't changed.

SPEAKER_00 24:50

What does a typical breakfast look like in the bag pillow home?

SPEAKER_01 24:54

Yeah, I really try to get our kids and myself, you know, 30 to 40 grams of protein. This morning I had four eggs, I poached four eggs. Um, and then I we do use these, um, they're lower carbohydrate. They're it's a great product. Someday we ought to do just quick reviews on different products that are out there. There's a product made with um avocado oil, cassava flour, psyllium husk. I think those are the only three ingredients. And there's like 10 grams of carbs in one of these wraps. They're the name of the the name of the uh of the brand is Rise and Puff. That's the name of the brand. Um, they're hard to get. You kind of got to get them online. But I heat up one of these wraps um and I put four eggs and probably three to four ounces of mozzarella cheese. I melt the cheese on the wrap, then I put the four poached eggs on it, and I try to get you know all my kids to eat to eat that combination, as well as myself, and that you know, that gives around you know, somewhere between 30 and 40 grams of protein. And you know, there's only 10 grams of carbohydrates there, and it's you know, it's a safe starch in the way of cassava flour. And then, you know, I'm sure I'm insured that my kids are getting those eggs, you know, which are just so valuable for kids and in their development. So that's a really common breakfast. Or I'll take um, I'll take full fat yogurt and I'll take roughly a half a tub, so about 16 ounces or so, and I'll put in like 40 grams of whey protein, and it really thickens up the yogurt. You let it sit for just a couple minutes, and that fully solubilizes the whey protein, and you'll actually see it start to bubble a little bit as the um, as the bacteria in the yogurt starts to actually work on the very small amounts of lactose uh that's in that whey protein. And that's gonna give me about 50 to 60 grams of of protein. So those are two really common breakfasts that you know I know kind of get me going in the right direction. And I feel so much better on those days. Uh recover better from my workouts. I, you know, I'm pretty active in the late afternoons or evenings with coaching. And I know when I when I don't have one of those kind of one of those types of breakfast, Mark, that kind of give me the foundation for the day, I really feel it later in the day. And I want to eat a lot more food later in the day, which I don't want to do. But, you know, that's the thing about this that we haven't talked about, which is most people are going to have a certain set point of calories that they're gonna, that their body needs or that they're gonna be driven to consume, right? So the downside to not eating until noon is a lot of people have that much, much greater cravings and uh and that drive to eat so much more food in the evening that if you can kind of shift everything forward and get like, say you can get 600 or 700 calories in the in the first two or three hours of light, your body's much, much more content not eating at eight o'clock or nine o'clock at night. You know, I'll come home some days where it's like, you know, for whatever reason, crazy morning schedule, and I'll find myself in the kitchen at eight o'clock or nine o'clock at night because we've just been gone all day. And you know, you feel like you got to eat something, you're you're ravenous, you don't feel like you can fall asleep. And then those are the nights where, to your point, I end up eating food, you know, after dark and I don't sleep very well. So you can you can really feel and experience everything we're talking about. And I'm sure most of our listeners understand this. Um, you know, I've got I've got athletes that I work with that wear these sleep quality monitors, many of which you're very familiar with, right? And they say that when they eat at you know, nine o'clock, ten o'clock at night, that their heart rate variability is very poor, their sleep quality is that's where they get their lowest scores. So I think there's a lot of different ways people can, you know, can immediately connect with with the the narrative here that we're sharing, right? Which is that if you want to sleep better, you know, you want to eat your food, your dinner earlier, if you want to get a better weight, if you want to have build more lean body mass, you want to eat more of your your protein early in the day. It's all aligned. It's all aligned. With biological aging is something that I think a lot of our listeners are concerned with. Everybody wants to, you know, age at a healthier trajectory. Um, but if you want to sleep better, you want to have more energy, you want to be stronger, you want to have better bone density. I mean, you just pick your pick your area, right? You just want to be the best version of yourself, give it a try. You know, just fight the urge to uh to just kind of get going into your day without eating. And I I talk to people about this all the time. If you give yourself a couple weeks with a um with a substantial high protein breakfast, you really find that you miss it when you don't have it. It becomes much easier because a lot of people tell me, and I don't know if you you've probably heard this over the years as well, people say to me, I just don't feel like eating in the morning. Well, in a way that's kind of like, you know, you haven't really given it enough time to sink in. It's like when people say, you know, I just don't like to exercise. I'm like, well, yeah, I can understand that. But once you start exercising, you love how you how it feels. It's the same thing. You got to just give yourself a chance to adapt to that first morning meal.

SPEAKER_00 30:10

Such great points, John. And and these are such easy things to play with and and to see how one does with it. Um Yeah, Mark, I like that.

SPEAKER_01 30:22

You always say, right, you're an N of one. Experiment with it, right? Yes. What's the downside?

Eating Window Length And Aging

SPEAKER_00 30:29

Exactly. Uh in much the same way that eating an earlier breakfast is is very important to slow biologic aging. Uh, eating dinner, supper earlier in the day, as we've talked about, um, also comparable uh benefits with respect to the slowing of biologic age. And um most of the findings in the study with respect to the eating window uh suggested, and I'll come back to the graphic of the study, uh generally feeding durations of less than 10 hours. So let's say breakfast at eight, um, you know, you'd be looking at a supper up to like 6 p.m. Um it was that 10-hour window that best predicted slowing of biologic age for uh total body, heart, liver, kidney, and the inverse of that uh once that window expanded, and this was a kind of a linear relationship, particularly when that window started getting up uh above 12 hours to 16 plus hours, so that essentially a person is eating something throughout the day except when they're actually sleeping, uh, dramatic uh um increases or acceleration of biologic aging. And so the bottom line, right, and it like so much of the great ancient wisdom. I know my grandmother and mother, and certainly probably any mother, grandmother who love their kids and grandkids uh of the last uh several hundred generations, uh just sort of understood that breakfast was the most important meal of the day. Um and I heard that every morning from my mother. Heard it from my grandmother when I lived with her, and they just sort of knew. Um and it was it was almost always included an egg, eggs, it almost always included whole fat dairy. Um, it almost always included some type of meat. And uh that was they just sort of understood that. Um and as we often talk about, John, there is this sort of curious loss of ancestral wisdom that we uh uh and so today it's like oh, you know, it it one might not even think twice about having their first meal at noon, um, thinking that uh this is a good thing. And uh and in years past, I was part of that club.

SPEAKER_01 33:23

Um and and Mark, I'll just say from experience that you know, over the years of working with with clients, the most difficult weight loss clients or challenges have been those who just can't adapt to that early morning uh meal pattern. You know, the folks that just find it, whether it's due to their schedule, whether it's due to their just lack of interest in food, or they don't feel like they can tolerate food early in the morning, those are the folks that I feel have the most difficult time really changing body composition and getting the metabolism they want. And I would, I would honestly, at this point in my you know, career with my experiences, I would say I'd have a hard time answering the question, what's more important, what you eat or when you eat. I mean, I and again, you know, of course, I think it's really important what what somebody eats, but if someone were to shut it down at five o'clock at night, not eat after five o'clock, I'd have a hard time betting that that wouldn't be more favorable in the end than what it is they were eating, but they're eating it really later.

SPEAKER_00 34:35

Yeah. Yeah, and I would suspect, John, uh, like the research is seems very consistent, those that struggle most with an earlier breakfast uh are those that have the most disrupted circadian biology. And um in much the same way that uh you know, when I one of my uh favorite questions for people, particularly in the domain of sleep, is do you require an alarm clock to get up in the morning? And when somebody tells me, oh, I can't get up without an alarm clock, and I have to hit it three or four times each morning. Uh that to me is a is an everyday experience of life that is a huge flashing red light with respect to how disrupted your circadian biology is.

SPEAKER_01 35:31

Yeah.

Biological Age Clocks Explained

SPEAKER_00 35:31

And on any given morning, that may just feel like a nuisance, um, but in reality, it is a manifestation of something much deeper going on. And so to the point that you made, John, really one has to allow themselves some adaptation because once you've hacked those deeply conserved circadian biologic patterns, um while you can totally readdress it, uh it can take it can take some time. It can take several weeks, even. And so uh one has to be sort of patient when they're looking to challenge a a current lifestyle pattern that that may not be serving them well. And um so those are all such such good points. Um let's just briefly pivot, John, as our time is a bit limited, but with um uh just some of the current uh research around these biologic aging clock measures. And the way that I think about this is that there are two general categories of biologic clocks. Uh one category which has become very popular and is the epigenetic clock. This essentially involves, usually it's a um a swab of the of the cheek or maybe a saliva sample where they get um cells from that from your cheek and measure the epigenetic methylation patterns, right? So we talk a lot about uh in DNA how you've got these genes that code for proteins, but most of DNA, in fact, has a regulatory function of those protein-coding genes. And one ways in which humans and mammals adapt how proteins are produced through DNA translation is through methyl attachment, these methylation groups. Uh and so uh there's a lot of data now the last ten years looking at various techniques of measuring these methyl patterns. And again, through AI and very high computational capacity, they can uh evolve and develop algorithms that allow more accurate prediction of one's aging beyond chronologic aging using these methylation patterns. So it's really a kind of a DNA test, if you will. The functional biologic aging clocks are a second category that doesn't require a cell, a cell sample. Most of this can be done just with blood work and commonly obtained blood work, which is why it's become such a popular tool for these clinical investigators. People in the NHANES database, uh people in the UK Biobank database have all had basic blood work uh chemistries and CBC, a blood count of the red blood cells and white blood cells. And these methodologies leverage that commonly available blood work data, along with often blood pressure, um uh heart rate to give you a biologic age. And so it's a different methodology, but one that tends to be a little bit uh logistically easier because one can take existing blood work that's already been done, and then use these more refined um algorithms to assess and validate um biologic age. And so um one of the two most common functional uh tests are the KDM method, this Clamara-Dubal method, um, which was published a few years back. And that's what the investigators of this lifestyle rhythms and biologic aging study applied. There's also the pheno age, which is um, these are very similar. Um pheno age is also a functional test that based on blood work um can give you your biologic age. But because this blood work also looks at organ-specific function like a creatinine for kidney function or liver function tests for liver function, uh, it these methodologies also allow you to give an organ-specific age. And I think it's fair to say that you know, we're still in the early iterations of this, but there have already been three generations of epigenetic clocks. Uh you know, we're all this knowledge explosion. And so these are going to continue to rapidly evolve, but they're getting more accurate. And I think they will be nice, non-invasive, inexpensive ways for people to track beyond how they feel, beyond what might be a disease measure that they're managing or treating, give them a sense of just sort of globally, how is their biology relative to the average population? And in my experience, it can be a powerful motivator for behavior change when you start to at the age of 30 or 40, uh, consider the fact that by the time you're 60, uh, you're looking at what could be uh a biological age of 80. Uh so you know, we're we're all trying to outrun uh, you know, father time or mother time. Um research would suggest that healthy lifestyles, healthy mindsets, healthy, you know, all the things that we talk about, um, those sort of ancestral paleo adapted lifestyle patterns very much seem to predict um uh uh longer life and better quality of life or or health span. And so um um just categorically, these are um um um and then again this this KDM, this Clamara Dubell method, um um has stacked up very well uh as compared with some of the first generation epigenetic clocks. Um I think I think Stephen Horvath, if I have his name right, Dr. Horvath at UCLA developed one of the first generation um uh epigenetic clocks. That was about 10 years ago. Uh and so these uh blood-based methods, blood test-based methods are are generally considered today even more accurate than those earlier epigenetic clocks at predicting health outcomes, mortality, uh, and maybe slightly better than some of the second generation epigenetic clocks. And again, uh this these methodologies continue to evolve. Um the current thinking in my review of the research, John, is that epigenetic clocks seem to excel at predicting chronologic age with very high precision. So the correlation rates between a chronologic age and a biologic age for the average, you know, the general population tend to be very precise with epigenetic clocks. But these functional tests, like the KDM method and the pheno age, seem to be really good at capturing uh sort of quality of life, health span-related characteristics, are emerging as important predictors of mortality, uh, all cause mortality, as well as disease specific mortality, cardiovascular, and say cancer, for example. Uh, and again, um uh these these functional methods do take into account blood pressure and blood glucose and Um so um you know, all things considered, they're very good methods. And this is just the pheno edge, the second sort of functional test that I think is most popular.

SPEAKER_01 44:14

And uh most labs now are putting some algorithm together with this, right? My function health and all those exactly.

SPEAKER_00 44:23

So when you when you have blood work done at some of these more functional labs, uh in addition to the individual results, they'll give you your biologic age. And these are the algorithms that they are using. And and again, it's uh blood work. The phenolage looks at a different sort of cadre, some of the same things, but not entirely the same from liver and renal function, uh, markers of inflammation. Um the pheno age um looks at, and I find this really interesting, John, because these are results that come with every complete blood count, CBC, but they tend to get ignored by clinicians. You know, usually you're looking at the white count and your hemoglobin and platelet count. Um over half the CBC tends to get overlooked. Uh there's some validity to many of the measures, like uh what percentage of your white blood count are lymphocytes, which are immune cells. What per what um uh when you look at your red blood cells, what is the the size, the volume of those blood cells? People that have more uniformity, homogeneity, uh uh that would tend to predict slower biologic aging as opposed to a C.

SPEAKER_01 45:47

Yeah, and a lot of that has to do with methylation, as you know, right? You know, and so the nutrient density of the diet comes into play here as well. You know, a lot of people, as you know, are somewhat deficient in those methyl donors that they need for some of these key processes. And so that's what's beautiful about some of these algorithms, is it does bring in, you know, different facets, not just when you eat, but also the nutrient density of the diet. Exactly.

Meal Timing Study On Weight Loss

SPEAKER_00 46:16

And so again, uh I think these are all really uh good and continuing to improve methods for uh assessing biologic age. If any of our listeners are interested in that, um generally you'd have to purchase a separate kit to measure your epigenetic age. Insurance is not going to cover that in the current state. Uh as I said, many of the blood tests that you've already had could be used in the pheno age and the KDM methodologies. So for functional physiologic decline, mortality risk, the KDM and phenol age as of today are generally considered as are more accurate for cellular aging, for chronologic age estimation, uh, you know, the epigenetic clocks are generally more accurate. And and so um people people can think about um you know considering this as part of their uh database, their portfolio of self-care and biomarkers and and measures. And this can be obviously very useful. Uh I think these tests are most useful for trending, John. Um trending to get those patterns, those trajectories, but also trending to demonstrate just how powerful lifestyle can be in slowing one's uh uh biologic aging, which is what you know we all aspire to do. And this is uh just a uh uh another study that uh I think you had shared with me, John, and and a study from Spain uh again looking at timing of meals, uh not focusing on biologic aging uh per se, but more on obesity and metabolic risk. And uh again, not surprisingly, and I'll just jump to this graphic which summarizes um this was uh uh looked at individuals over 20 weeks, over about uh five, six months, and looked at the uh correlation, of course, between those that ate early, the later eaters, both late breakfast, late dinner, early breakfast, early dinner, and looking at body weight in kilograms over time. Uh, and you get again pretty early on, you can be, you know, a month uh you start to see a separation where the late eaters just aren't, you know, they start to plateau, right? You can only go so far. And I'm sure you, John, and the countless number of people you've consulted with uh will frequently come to you because they've had an initial result for whatever it was that they were doing, but they hit the wall, they hit the plateau and need help looking at how they can move beyond that. Uh, while you see not only a uh a significant separation with the early eaters, but it's a trend that seems to continue. There's this sort of this linear dose effect, uh, which I find um important. And just another graphic, again, um how uh you know, sort of moving away from calories in, calories out, right? Meal timing, you know, these studies aren't really looking at the the uh meal quality. They're not even looking at the number of calories you're consuming, they're just looking at the timing of the meal. And so, again, uh early breakfast, uh uh and here on this graphic, they're looking at the midpoint of total caloric consumption for the day. And so these are people who've hit their midpoint generally uh by midday and have completed their caloric consumption minimum a few hours before bedtime, uh, as opposed to individuals getting up late, uh, eating late, um, first meal, last meal, how their midpoint of caloric intake for the day is very late in the day, late afternoon. Uh, they're just at their midpoint. Uh, and so you see that skewing on the diurnal rhythm toward much later in the day. And um this is this DLMO is when dim light melatonin um uh starts to turn on. People think melatonin starts when we fall asleep or at the time that we're falling asleep. Our bodies start producing melatonin at, you know, as the sun is low in the sky. Uh so metabolically, biologically, the nighttime cycle, at least as measured by the emergence of dim light melatonin, uh, is you know, a few hours before bedtime. And so that may be one reason why one sees disruption eating too close to bedtime, is that um that melatonin signaling um is is very disrupted if you don't allow those few hours. And again, the phenotype uh is a very different phenotype. Same person, a very different trajectory of health. And um I'll pause there and let you comment, John, and then and then we can end with a uh kind of a summary slide putting this all together.

Light At Night And Melatonin Timing

SPEAKER_01 51:52

Yeah, I mean, again, we touched a little bit about you know, first-year college students. I had a I had a physician uh that I knew from Japan, this is quite some years ago, uh, that said, hey, you know, in Japan, you know, when world champion sumo wrestlers are training, they're not allowed to eat until something like you know, after afternoon. It was like whether it was one or two o'clock in the afternoon. And, you know, they can eat all the food, you know, that they want, all the bowls of white rice and everything. But if that food is eaten, you know, early in the day, they tend not to gain the type of weight that they need to to be a you know champion sumo wrestler. And that always, you know, I always thought that was astounding. Obviously, there's no there's no double-blinded placebo study here that I'm referring to with this. It was just something that is anecdotal that I have heard now. I've also read it uh somewhere, I can't remember where, but you know, so you know, you have all these different examples, right? That I think these studies now are illustrating. And the point that I like that you just made about that one, Mark, which is you know, that dim light melatonin, you know, secretion that starts, let's just say around five o'clock or so. Yeah, you start compounding these things, right? So, you know, largely we're talking about time-restricted eating here and trying to shift that around so your windows earlier in the day. But I think for our listeners' sake, I'm sure that they can connect the dots now. And you start thinking about the explosion, the exposure to blue and white light late in the day, right? You know, all the fluorescent lights that a lot of people are under, you know, after seven or eight o'clock at night, they're eating at you know, nine or ten o'clock at night. You know, it's a wonder that anybody sleeps that has that pattern. And now you just you start thinking about all the efforts to really help people with better, you know, there's all these different attempts, through sleep studies, and but I mean some of this stuff is somewhat blocking and tackling, right?

SPEAKER_00 53:55

Blocking and tackling, such great points, John. And and as we reflect on other aspects of lifestyle that influence circadian biology, you see how quickly these this compounding takes effect with um, we know that eating a late-day meal under blue light um gives you a different glucose and insulin excursion. Um, you'll have higher sugar. Same meal consumed at 9 p.m. will give you a much higher insulin glucose response than eating that meal at say 5 p.m. Um in much the same way that we know people who harbor maybe uh more fear in that fight-flight mode. Um, for whatever reason, I mean there are so many reasons to provoke fear from you know just hearing the news on any given day to worrying about the bills, worrying about one's health, maybe being a caregiver for a loved one, um how that um uh you know, those high cortisol, high adrenaline states, which are best experienced earlier in the day, not 24-7, uh, further add another layer of complete disruption of circadian and circadian biology. And and so it it you know, we sound like broken records, but the modern environment is so heavily stacked against us that if we're not mindful of how we are um uh behaving and what our lifestyle choices are, um that that default mode, that that architecture of modern life will assume itself. And um you're you have now handed over your biological legacy to a set of conditions that for most, even if you get away with it at a certain age, it will catch up with you because disrupted biology won't go away unless you do something to make it go away. And uh and and so you right, you just see how does anyone sleep at night? And you know, John, a lot of people don't.

SPEAKER_01 56:22

Yeah, that's a good point.

Practical Takeaways And Closing

SPEAKER_00 56:24

You know, yeah. Uh how how does anyone go without gaining weight? Well, you know, almost everyone is overweight now. Yeah, we we've looked at metabolic health. So how does anyone get through life without disruptions to their metabolic health? We know from the NHANES data that over 90% of Americans do not would not meet criteria for normal metabolic health. So the the phenotype, the epidemiology, is 100% consistent with all of these underlying mechanisms, much of which can be traced to gene environment mismatch, uh, this paleo approach that that that we like to sort of embrace. Um, and it's the elephant in the room. Um it at the same time that all of this is happening, um, there's a tendency to say, geez, you know, why? Why is this happening? Uh and to attribute it all to bad genes will do nothing but perpetuate the drivers. Um uh I'll just come back, John, for this last slide, and I'll let you I'll let you uh bring us home with with these uh with these uh conclusions, John. And so we've touched on this, but just to to conclude, it's sort of actionable tips that that people can do and um and some of the health benefits that will follow.

SPEAKER_01 57:44

Yeah, no, it's a good I think it's a good way to bring it home. I just, you know, again, I always say give it a try. You know, I a lot of people say I'm not that hungry in the morning or I just don't have that much of an appetite. Just work at it, just like you would anything else. It, you know, I'm not sure if it's gonna take, you know, like someone two weeks or two months, but I know people get there once they start to adopt the type of shift that you know that we've discussed. And uh, you know, I think socially it's challenging to not eat dinner after seven for a lot of people. That's when they're you know, more of the get-togethers take place. And you know, whether it's a family meal or it's some type of gathering outside of the home, I you know, I fully empathize with that, but do your best to eat less. And and one of the ways that people can have, you know, I think uh better control over that situation, Mark, for lack of a better description. I don't know, you know, if control is the right word, but is to eat more protein early in the day. And there have been countless studies, whether it's a human study or an animal study, if you give if you give any population of mammals like free choice to food, right? There's a certain amount of protein that needs to be consumed every day, or every species of mammal will overconsume every other type of food, right? A lot of times people are looking for protein with these meals, and this could really, you know, this would happen if it's outside of your control and you're going outside to some type of social gathering, you're going to some event, you're eating dinner with a large group of people, chances are those environments are not gonna serve the food that you and I, you know, generally advocate high protein, lower carb. It's gonna be the antithesis of that. So eat more protein early in the day to both help with you know the thermogenesis, the increased metabolic rate, and all the benefits you get from that, but also it's going to really help somebody have you know more restraint, I guess, more control, and be comfortable eating less if they do have to eat at a less ideal time, like you know, 7:30, 8 o'clock at night. You do all you can to eat, you know, your smallest meal at the end of the day. Uh and you know, I think this I you know it's death by a thousand cuts, right? But this is a big one. This is a cut that tends to bleed, you know, help, you know, people bleed out a lot more with this. You can really help yourself uh by putting a bandage or maybe a tourniquet on this cut. Uh, you know, some of the others we've talked about, whether it's you know, the exposure to blue and white light, critical as well. But I think eating at nine o'clock or ten o'clock at night for many people, it's the it's the linchpin, right? It's the one that the whole house of cards comes down.

SPEAKER_00 1:00:33

Awesome conclusion. And we we hope that uh our health edge listeners uh resonate with what we're sharing. I know it will. And um, please share this information with uh uh friends, family, those you love. Uh John and I have uh basically zero social media uh outreach. So uh so much of the Health Edge uh community is just word of mouth. So uh please feel free to share this information with those. The uh some of the studies that we've reviewed, the slide deck will be on our Health Edge podcast uh website, and we hope that is helpful to people. And uh more good news to use. And John, great seeing you and great. I love these topics, they're awesome.

SPEAKER_01 1:01:22

Um, I do as well, Mark. Thanks so much. Yeah, you have a great weekend, buddy. You as well. Take care, my friend. You too, love you. Bye. Love you too.