As the former Director of Research and Content at the International Peptide Society, Hannah recognized a unique opportunity for methylation-based age diagnostics. This insight led her to found TruDiagnostic in 2020, a cutting-edge company specializing in methylation array-based diagnostics for life extension and preventive healthcare. Today, TruDiagnostic serves functional medicine providers worldwide and boasts one of the largest private epigenetic health databases, with over 75,000 patients tested.

Driven by a commitment to research, under Hannah’s leadership, TruDiagnostic has spearheaded over 30 clinical trials exploring the epigenetic methylation changes in longevity and health interventions. Additionally, she shares her wealth of knowledge through [Everything Epigenetics](https://everythingepigenetics.com/), offering valuable insights into how DNA regulation impacts health.

Here, we explore the future of longevity, the power of epigenetics, and the transformative potential of innovative healthcare technologies.

One intriguing aspect of taurine is its potential to vary in production between individuals. Furthermore, studies indicate that taurine levels may decline with age. This brings us to the focus of this week's episode of humanOS Radio.

Guest

We are delighted to have Vijay Yadav, an Assistant Professor at Columbia University's Department of Genetics and Development, as our guest. He is the senior author of a fascinating new study published in Science, which explores the connection between taurine and the aging process.

Yadav and his team conducted measurements of blood taurine concentrations in mice, monkeys, and humans at different ages. Their findings revealed a consistent decline in taurine levels associated with aging across all species. In fact, the reduction was significant, with elderly humans exhibiting an 80% decrease in taurine compared to younger individuals.

The crucial question posed by the authors is whether these changes are mere correlations or if they play a causal role in the aging process. In other words, do declining taurine levels contribute to physiological aging and age-related diseases, or are they simply associated with them?

If taurine reductions do indeed cause aging, restoring taurine levels to that of youth could potentially extend both lifespan and healthspan. This means not only living longer but also living better.

To begin unraveling this question, Vijay and his colleagues conducted a series of experiments. To discover their findings and delve deeper into the relationship between taurine and aging, we invite you to listen to the interview on humanOS Radio.

Indeed, perhaps more accurate than the number of years that you've been alive (i.e., your chronological age). How can this be?

Well, it has been known for some time that the microvasculature of the retina can offer a window into the health of the circulatory system as a whole. Subtle changes in the retinal capillaries have been shown to provide the earliest signs of a vast array of diseases, even conditions that are not specific to the eye, long before symptoms emerge.

Incredibly, a new study suggests that images of your eyes might soon be able to yield insight into how long you have left to live – in time for you to do something about it.

On this episode of humanOS Radio, we welcome Pankaj Kapahi back to the show. Dr. Kapahi is a professor at the Buck Institute, an independent biomedical research institute that is devoted to research on aging. His lab has been exploring how nutrient status influences health and disease, and particularly how nutrients affect age-related changes in tissues and disease processes.

In our previous interviews with Pankaj, we have discussed his work examining how advanced glycation end products (also known as AGEs) drive the aging process. To that end, Pankaj has developed a novel formulation that combats the endogenous formation of AGEs in the body, known as GLYLO, which you can now purchase for yourself.

But how can we gauge the effectiveness of these sorts of interventions in humans? To that end, Dr Kapahi has turned his attention to techniques for measuring biological age (as opposed to chronological age).

Very recently, Pankaj and his colleagues have developed a retinal aging clocking, which they have dubbed "eyeAge." They found that eyeAge could predict changes in aging at a granularity of less than a year – a much shorter timescale than existing clocks. Retinal imaging is inexpensive and non-invasive, and widely accessible (if you've ever had a standard eye exam where they dilated your pupils, you have already experienced this diagnostic tool yourself).

It's not hard to imagine a future in which annual retinal scans could be used to tell you your current biological age, as well as the rate at which your tissues are aging. With this information, you could figure out whether your current lifestyle approach or medical interventions are working, and make changes as needed. And on a population level, we could use accumulated longitudinal data from retinal scans to identify new avenues for combating physiological aging.

To learn more, check out the interview!

This powerful combo now makes up the product GLYLO, and preliminary testing of GLYLO in rodent models revealed, sure enough, that the combo reduced glycolytic byproducts, improved insulin sensitivity, extended lifespan by 30-40% when administered late in life, and reduced caloric intake, and promoted weight loss. Importantly, this effect was shown to be independent of peripheral hormones like leptin and ghrelin. In fact, injecting ghrelin into mice treated with GLYLO did not result in increased energy intake - suggesting that GLYLO was changing how the hypothalamus responded to ghrelin. In other words, reducing methylglyoxal, through GLYLO, appeared to be lowering their body fat set point.

In particular, she has explored how the ratios of potassium to sodium, as well as base to chloride, differ in the modern diet versus the ancestral diet, and how these changes may be linked to greater risk of chronic disease as we get older. 

Anthropological evidence suggests that ancient hominids consumed far less sodium and far more potassium, and specifically more potassium alkali salts (primarily from wild plants). The reduction in potential base in the modern diet increases the net systemic acid load, and this in turn may take a physiological toll in myriad ways. Chronic acid load appears to play a role in osteoporosis, hypertension, cardiovascular disease, and even age-related decline in growth hormone secretion.

Naturally, lots of questions emerge from this idea. Which nutritional components determine whether a diet is net acid-producing? And what can we do about it on an individual basis? Should we take potassium supplements to rectify the imbalance? Could restoring a healthy sodium to potassium ratio be a hidden anti-aging tool?

To learn about how you can live a more alkaline life, check out the interview!

Brad has been leading research behind transdermal delivery of carnosine. Carnosine is a buffer of acidosis in skeletal muscle, and exercise trials have shown that higher levels of carnosine in muscle can help delay the onset of fatigue during exercise associated with acidosis and enable athletes to work longer at a high intensity. But oral supplemental methods of boosting carnosine - such as beta-alanine - can be cumbersome and time-consuming. You have to take relatively large, divided doses every day for up to 4-6 weeks before you see a benefit.

To that end, he helped with the research and development of LactiGo, the first effective topical carnosine product for humans. LactiGo is a fast-acting gel which delivers carnosine to skeletal muscle through the skin, and tests of this product are pretty persuasive. In one double-blind pilot study, elite soccer players were able to cross the finish line up to 5.9 feet sooner when running the 40 yard dash. And this was just after a single application of the product!

To learn more about how carnosine works, and about LactiGo, check out the interview!

We also know that the gut plays a role in the immune system. In fact, it is thought that over 70% of the body’s immune cells reside in the gut. Throughout life, gut microbes shape and regulate the immune system, and the immune system in turn guides the composition of the flora in the gut.

We think gut microbes work a lot of their magic by generating crucial metabolites, and these metabolites can help modulate the immune system response to invading viruses. For example, one remarkable study from a couple years ago found feeding mice a high-fiber diet increased their probability of survival when the rodents were infected with influenza, and it appeared to be due to increased production of SCFAs.

So, does this mean that eating lots of fiber can help protect us from getting sick? What other components of the diet might modulate the immune system? And how does aging figure into this puzzle - could maintaining a healthy gut microbiome help protect older adults, who are generally at greater risk of infection?

On this episode of humanOS Radio, Dan speaks with Lucy Mailing. Lucy has a Phd in Nutritional Sciences from the University of Illinois. Her research focused on the effects of diet and exercise on the gut microbiome and gut barrier function in states of health and disease.

She recently wrote a broad overview on what we know - and what we don’t know - about the role of the gut in the immune system, as well as some ideas of what we can do to support the gut-immune axis. This is, obviously, a very important and painfully relevant topic, so we knew we had to have her on to discuss it.

To learn more about how gut health affects resistance to infections, check out the interview!

Her research explores how altering aspects of sleep can produce changes in mood and emotional regulation, particularly in those with major depression. Jennifer’s work has led her to investigate a long-recognized but poorly understood clinical paradox: Certain individuals actually experience mood improvement in response to sleep loss. You read that right - total sleep deprivation has been shown to have antidepressant effects. Remarkably, an estimated 40-60% of people with major depression may experience significant improvements in symptoms.

Of course, these benefits dissipate once the patient’s sleep is restored, which is probably why interest in this as a therapy has lagged. But Jennifer and her colleagues are starting to figure out why precisely sleep deprivation seems to improve mood, and which individuals might stand to benefit from sleep manipulation. You can imagine that gaining insight into this strange phenomenon may eventually lead to new treatments for depression and other mental disorders. To learn more about her fascinating research, and what is on the horizon for this work, check out the interview!

Many common supplements, like caffeine, have been studied in the context of immediate performance enhancement, and are used with that goal in mind. But the effect of chronic supplementation, particularly in endurance training, is not as well understood. Furthermore, it is not as clear how performance-enhancing supplements might influence the adaptive response to exercise training. Training-induced adaptations are the product of repeated stimuli from exercise sessions, as well as accumulated changes in gene expression, which gradually result in adaptive changes like greater muscle mass as well as more efficient muscle contractions.

Dietary intake of certain substances can, in theory, affect training adaptations in a couple different ways. They can achieve this by simply increasing the exercise stimulus from a single training bout - basically just enabling an athlete to train longer or harder, or reducing perceived exertion. But they may also be able to affect gains in endurance by altering cellular responses to exercise-induced stress. For instance, supplements like buffering agents and antioxidants may modify the cellular signaling response to training by affecting acid-base balance, reactive oxygen species signaling, or redox status. Importantly, these changes in cell signaling may not be universally beneficial from the standpoint of adaptation.

This raises a number of interesting questions. How significant is the impact of these supplements from a practical standpoint? And how do we separate acute effects on training duration and intensity from chronic effects on training adaptations? Is it possible that a supplement could simultaneously make it easier for an athlete to exercise hard, but also have effects on cellular signaling that actually have a long-term negative impact on the adaptive response to training?

On this episode of humanOS Radio, Dan welcomes Jeff Rothschild to the show. Jeff is a Registered Dietitian with a Master’s in Nutrition Science, and is a Board-Certified Specialist in Sports Dietetics (CSSD).

He has worked with an impressive array of athletes - his clients include multiple Olympians, State Champions, collegiate All-Americans, and professional tennis players, as well as recreational athletes and folks who are trying to complete their first triathlon.

Jeff recently wrote a fascinating review exploring the impact of dietary supplements on adaptations to endurance training. He came on the show to discuss his findings, and what they might mean for athletes and generally active people who want to maximize the time and effort that they dedicate to their training. To learn more about how various nutritional supplements might affect your training - both short and long term - check out the interview!

But what about mushrooms?

Mushrooms have historically not held a prominent place among the list of superfoods. But if you take a closer look, I think you’ll find that the humble mushroom actually has a lot going for it.

A single cup of whole white mushrooms - like the kind you usually see at grocery stores - contains just 21 calories, but around 16% of the recommended daily value of selenium and 33% of the daily value of vitamin D. They are relatively high in potassium and low in sodium, and they are a decent source of essential amino acids given their caloric density.

But of course, the most compelling benefits of mushrooms do not show up on a nutrition label.

Edible mushrooms are rich in polyphenols, and the antioxidants glutathione and ergothioneine. Mushrooms are also an excellent source of a class of polysaccharide called glucans. Glucans can also regulate the immune system, and this is where mushrooms really shine.

For instance, children who were given a supplement with beta-glucan from mushrooms showed significantly higher levels of natural killer cells than those given placebo, and were also significantly less likely to develop a respiratory infection.

Mushrooms have been underappreciated. Which is why Dan was pleased to welcome Jeff Chilton to the show.

Jeff is sort of a trailblazer in the area of medicinal mushrooms. He recognized the unique value of mushrooms to human health long before most people. Jeff studied ethnomycology - historical uses and sociological impact of fungi - at the University of Washington in the late 1960s, then went on to work on a commercial mushroom farm in 1973.

Over the following decade, he became the production manager, responsible for the cultivation of over 2 million pounds of agaricus mushrooms per year. He was also involved in the research and development of shiitake, oyster, and enoki mushrooms, which ultimately resulted in the earliest sales of fresh shiitake mushrooms in the US in 1978.

Fast-forward to 1989: Jeff founded Nammex, a business that introduced medicinal mushrooms to the US nutritional supplement industry. Nammex extracts are now used by many supplement companies, and are noted for their high quality based on analysis of the active compounds.

Given his background, it is hard to think of a more qualified person to speak to about the mushroom industry, and the health-promoting power of mushrooms. Check out the interview to learn more!

In our previous interview, we discussed his research on light and timing of biological rhythms. He and his colleagues determined that brief, intermittent flashes of light have a much bigger impact on clock timing than continuous light exposure. This has interesting implications for shift workers, as well as for people who travel across multiple time zones and are subject to jet lag. In theory, you could expose yourself to brief flashes of light while you are asleep and effectively trick your brain into adjusting to a new time zone. Pretty cool.

But could it also be useful for social jet lag - meaning a chronic misalignment between the biological clock and the time when one is forced to be awake and active? In particular, could it be effective for teenagers who have to get up to go to school at a time when their body is driving them to sleep?

To answer that question, Jamie and colleagues conducted a two-phase, randomized controlled clinical trial testing how exposure to brief flashes of light affected sleep onset and total sleep duration in high school students. Here’s what they did:

The researchers recruited groups of teenagers who had expressed difficulty going to bed and waking up early. In phase 1 of the trial, 72 participants were randomly assigned to two groups. One group received 4 weeks of light therapy, delivered from a device in the teens’ bedrooms (3-millisecond light flashes every 20 seconds during the final 3 hours of sleep). The other group was administered 4 weeks of sham light therapy (three bright flashes of light per hour, which isn’t enough to affect the body clock) as a placebo. This protocol was largely ineffective - neither sleep timing nor duration were significantly altered in the experimental group.

Zeitzer and his team switched things up a bit for the next phase. In phase 2, the subjects received a slightly different light therapy (3-millisecond light flash every 20 seconds during the final 2 hours of sleep). But in addition, the researchers had the adolescents attend four cognitive-behavioral therapy sessions to try to motivate them to go to bed earlier.

Happily, this combination of interventions actually worked! The light therapy plus CBT moved sleep onset 50 minutes earlier, and increased nightly sleep time by an average of 43 minutes. Very impressive.

To learn more about the study and what it means, check out the interview!

Presently, she is a professor and researcher at the Buck Institute, an independent biomedical research institute that is dedicated to investigating aging and age-related disease. Her lab is working on identifying novel therapeutics to delay or prevent the age-related molecular processes that drive neurodegenerative diseases. For example, she and other researchers at the Buck have been investigating compounds that could clear out senescent cells, which have been linked to age-related functional decline, as we have discussed previously on several shows.

Recently, Julie and her colleagues received a grant from the NIH to examine a natural bioactive known as urolithin A. Urolithin A does not come directly from the diet - it is actually a metabolite that results from the biotransformation of ellagitannins and ellagic acid via the gut microbiota. These phenolic compounds are found abundantly in edible plants, most notably in pomegranate, walnuts, berries, tea, and fruit juices (as well as certain types of wine).

In animal models of aging, urolithin A has shown great promise. Older mice that were given the compound exhibited a 42% improvement in endurance while running, compared to control rodents of the same age. And nematodes that were exposed to urolithin A experienced a 45% boost in lifespan. And the first clinical trials in elderly human subjects suggest that the compound is safe and effective for reversing age-related muscle decline.

So what makes urolithin A so powerful? It appears to enhance autophagy, the natural mechanism through which cells effectively cleanse themselves by removing dysfunctional proteins and cellular components. This property makes it an enticing therapeutic compound for addressing neurodegenerative disease. One of the hallmarks of Alzheimer’s disease is the accumulation of irreparably misfolded proteins in the brain. It is thought that deregulation of the autophagy pathway with age leads to reduced clearance of these broken proteins, which in turn leads to the formation of toxic aggregates that are typically found in deceased patients.

Unfortunately, the capacity to generate urolithin A also appears to decline with age. To that end, Julie and her team plan to try to rejuvenate the gut microbiota of older mice using targeted probiotics, which should enhance production of urolithin A. They will then track neuropathology, memory loss, and mortality in a rodent model of Alzheimer’s disease, and compare outcomes in mice treated with urolithin A and controls.

To learn more about this fascinating research, check out the interview!

It’s easy to see why high-achieving people throughout history - like Thomas Edison and Benjamin Franklin - aspired to get by with less of it.

Even today, people who are trying to maximize productivity are prone to shortchanging sleep so they can get more done. Twitter founder and CEO Jack Dorsey, for instance, reported he was only getting four to six hours of sleep per night in 2011. I’m sure you can think of plenty of others who have made similar compromises.

For most of us, though, this is not likely to be a winning long-term strategy. For one thing, we know now that sleep loss increases our risk of chronic disease, including diabetes, atherosclerosis, obesity, and more. Inadequate sleep duration and poor sleep quality are linked to most of the great maladies that plague the modern industrialized world.

But even beyond that insidious physical toll, research is now revealing that sleep loss also has a negative impact on our cognitive abilities. We need sleep for focus and attention, for staying alert, for learning and remembering things, and for a host of executive functions that are required to be at our best at work and in other endeavors. So, you might gain an extra hour or two if you cut out some sleep, but your ability to perform mentally during that time may be compromised, and you may actually get less done in the long run. Or the quality of your work may suffer.

You might think this doesn’t apply to you. But bear in mind that the cognitive impact of partial sleep loss can be quite subtle, and difficult to recognize in ourselves. This, of course, is why we need controlled studies to elucidate these effects.

In this episode of humanOS Radio, Dan speaks with Jeff Gish. Jeff has a Ph.D in Management from the University of Oregon, and is presently a professor of entrepreneurship at UCF.

His research focuses on the behavior of entrepreneurs, including the processes through which entrepreneurs decide to found new ventures and make business decisions. Recently, he has begun to explore how these processes are influenced by day-to-day variations in biological dynamics - including sleep.

He and his colleagues recently performed a series of elegantly designed studies which investigated how sleep, or the lack thereof, might affect two functions that are fundamental to the role of an entrepreneur: the capacity to generate new business ideas, and the ability to assess the viability of business ideas being presented to them.

These studies overall suggest that sleep plays a vital role in the cognitive processes behind successful entrepreneurship, and losing sleep makes it harder to recognize how a new technology or service might align with a market.

To learn more about the study and what he found, check out the interview!

Fortunately, due to global economies and remarkable advances in technology and agriculture, most of us living today in industrialized countries will probably never need to worry about starvation.

But ironically, we now must battle the consequences of excessive abundance of readily accessible food. All over the world, modern societies are confronting the challenge of obesity and diseases emanating from obesity.

An analysis of trends in adult body mass published in the Lancet puts the progression of this public health crisis into useful historical perspective: It revealed that the number of obese individuals has risen from 105 million in 1975 all the way to 641 million as of 2016. Over the past 40 years, we have gone from a world in which prevalence of underweight was more than double that of obesity, to a world in which people with obesity outnumber those who are underweight.

There has been vigorous debate on what aspects of our food supply are responsible for this relatively rapid shift in collective body composition. Recently, sugar has come under particularly fierce scrutiny, and understandably so. We do know that overconsumption of simple sugars can contribute to obesity and related diseases.

So what about fruit? Most types of fruit are naturally high in simple sugars, and we have essentially unlimited access to fruit year-round, even in the dead of winter. Could sweet fruit be a hidden contributor to the obesity epidemic?

And that brings me to our guest.

On this episode of humanOS Radio, Dan welcomes a familiar face back to the show - Stephan Guyenet. Stephan spent 12 years at the University of Washington researching the neuroscience underlying body fat regulation. There is perhaps nobody else, at least in our view, who has done more in recent years to help the general public understand the evidence related to energy regulation and weight control. This is why he is uniquely qualified to address the question of whether fruit actually does make you fat.

Last year, Stephan decided to answer the question of whether fruit was fattening in the most rigorous manner possible. Specifically, he wanted to look at the impact of whole, fresh fruit (as opposed to fruit juice, or other processed forms of fruit) on energy intake and adiposity. To that end, he conducted a systematic review of randomized controlled trials and prospective cohort studies, and that is what we have brought him on to discuss.

To learn about what he found, and what it means, check out the interview!

Our lives have changed drastically in too many different ways to recount here (and most of these changes are, arguably, pretty great to be honest). But for those of us who study health and human biology, our patterns of physical activity is perhaps among the most glaring. Surveys suggest that the average American spends about 13 hours per day sitting, and it is estimated that they typically get around 4774 steps per day. This stands in stark contrast to the tremendous amount of activity that was likely normal for our hunter-gatherer ancestors many thousands of years ago. Indeed, modern humans are not merely physically inactive relative to their own ancestors, but also compared to other free-ranging non-human mammals. And it is likely that we pay a substantial price in the form of chronic disease.

But the impact of our rapidly changing lifestyles probably affects us in other more subtle ways. One interesting manifestation of this is postural stress induced by our interaction with technology, which has been recently exacerbated by the ubiquity of smartphones, tablets, and other smaller digital devices.

A series of photos by the photographer Eric Pickersgill draws this effect into sharp relief. In these portraits, people are shown in otherwise mundane settings and events, only the cell phones that were previously clasped in their hands have been carefully edited out. What is striking about these pictures is the hunched posture assumed by virtually all of these individuals. With the smartphones extracted from the scene, it becomes really clear how awkward and unnatural this pose is. And yet so many of us spend much of our days like this.

Movement and how we inhabit our bodies is an integral part of the human experience, affecting our health, our performance, and our quality of life. And it goes way beyond just exercise.

That brings me to our guest. On this episode of humanOS Radio, Dan speaks with Aaron Alexander. Aaron is a manual therapist and movement coach who has worked with elite athletes, celebrities, and ordinary folks to relieve pain, increase strength, and optimize their movement patterns.

Aaron is a unique guy, with remarkable insight into the fundamental role of body posture and body movement in health and performance. The foundation of his message revolves around what he calls physical inhabitance. Physical inhabitance goes beyond activity - it encompasses the way that you sit, stand, walk, breathe, look, touch, listen, communicate, and generally the manner in which you occupy your body at any given moment throughout the day.

Aaron has authored a newly released book called The Align Method: 5 Movement Principles for a Stronger Body, Sharper Mind and Stress-Proof Life. This book lays out his integrated approach of functional movement and body alignment

Becoming aligned isn’t just about sitting up straight, or working out in a gym, or getting 10,000 steps per day. The Align Method is built around five basic optimizations that can be effortlessly integrated into your day:

-Floor Sitting

-Hanging

-Hip-Hinging

-Walking

-Nose Breathing

To learn more about the Align Method, and how paying attention to your physical inhabitance can enhance your health and performance, check out the interview!

Health-related goals are largely the product of long term modifications to how we live. And we generally don’t see an immediate payoff from these individual choices, at least not in the moment.

To paraphrase James Clear, it is only after your efforts have compounded over time that you start to see the payoff of these behaviors, for better or for worse.

But therein lies the problem - we are short-term creatures, and most of us aren’t able to easily identify these subtle benefits and costs when we are actually making these countless health-related choices every day.

So how do we overcome this?

Well, one tried and tested method is to track progress over time. This enables us to continuously see what’s working - and what isn’t working - and helps keep us accountable and committed to the behaviors that support what we are trying to achieve.

This is true of pretty much any health- or fitness-related objective that you could imagine, but it has particularly obvious application to body composition goals.

But for this sort of tracking to be really effective, ideally you would want the most accurate data, right? And with respect to body composition, not all methods are created equal. The scale, in particular, is a fairly limited and sometimes misleading tool.

And that brings me to our guest. On this episode of humanOS Radio, Dan speaks with Jason Belvill. Jason is the CEO and Co-founder of BodySpec, a company that offers DEXA scans on the West Coast.

DEXA (dual energy x-ray absorptiometry), as you probably know, has been demonstrated to be one of the most reliable ways to estimate body composition, and offers a number of advantages over other methods.

For one thing, the scan is able to differentiate between fat, bone, and fat-free mass. This means that it not only can distinguish between fat and lean tissue, unlike a scale, but it is also not subject to errors associated with variations in bone density. DEXA can also provide measurements for specific areas of the body, meaning that it can highlight differences in where fat is distributed.

So what’s special about BodySpec? Well, BodySpec offers the least expensive DEXA scans available in the country as far as I know ($45 per scan, compared to as much as $100 or more at other providers). They also perform RMR (resting metabolic rate) tests and VO2 max tests at some locations, so you can gain a lot of insight into your body and your performance if you pay them a visit.

But what truly sets BodySpec apart is that they are mobile. BodySpec has a fleet of DEXA scan trucks that can be booked at gyms, offices, and events throughout the west coast. So you can go to their storefront, or they can come to you.

Services like BodySpec make it extra easy to quantify your body fat, muscle, and bone density, and then track over time how your training and diet regimen is affecting all different regions of the body. To learn more about the merits of DEXA, and why you might want to get a DEXA scan yourself, check out the interview!

However, if you’ve ever spent time looking at health-related content on Twitter and Instagram, you’ll realize that conflating diet and medicine is a modern phenomenon. We like to think of certain foods and combinations of foods as exerting drug-like effects. And as we unveil the functional properties of natural compounds in edible plants - like flavonoids, just as one example - it’s easy for the lines between pharmacology and nutrition to become blurred.

But food is not a drug. And the distinction between the two becomes plain when we look at what happens when scientists try to elucidate the effects of dietary exposures on health outcomes.

To illustrate what I mean by this, let’s start with drugs. You probably already know that when scientists want to test a pharmaceutical intervention for safety and efficacy, the gold standard is a randomized controlled clinical trial. In this study design, participants are randomly assigned to either the substance being tested or a placebo (or usual standard of care). Neither they nor the individuals assessing their progress are told what they are taking.

Now, in theory, that would be the best way to examine the effects of diet as well. But if you stop and think about it, it should be pretty clear why it simply doesn’t work the same way for nutrition. For instance, it’s really hard to measure what people are eating outside of a lab, blinding is tough to do for studies involving food, compliance for diet trials tends to be poor, and the most rigorous studies are extremely expensive. Those are just a few of the most obvious roadblocks.

This mountain of ethical, financial, and practical limitations makes the field of nutrition horrendously complicated. That is why we have historically relied upon a combination of observational research (mainly prospective cohort studies), randomized controlled trials, and mechanistic studies. But some have recently questioned the rigor of this approach, and in turn are challenging major aspects of the guidelines for nutrition and health used around the world.

That brings me to our guest. On this episode of humanOS Radio, Dan talks to Michael Hull. Michael has an MSc in human nutrition from McGill University, and works as a full-time senior researcher at Examine.com. Mike writes and updates the Supplement Guides, maintains the company’s vast database of supplement studies, and blogs about various topics in the realm of health and nutrition (yep, sounds like our kind of guy).

You might remember that back in October, a series of studies were published that addressed the impact of red and processed meat consumption on a number of health outcomes. Importantly, these papers did not present any new evidence on the subject. Instead, they summarized the findings of existing RCTs and observational studies, and concluded that adults should continue consuming red and processed meat at current levels of intake - an obvious contradiction of most established guidelines. This, naturally, elicited a lot of turbulence online, from all across the diet spectrum.

So, who’s right?

Mike wrote an excellent piece for Examine.com sorting out these studies, and was kind enough to come on the show to discuss the papers and their implications.

As you’ll see, this is arguably less a discussion of the health effects of meat per se, and more about the aforementioned difficulties in performing nutrition studies and interpreting research.

To learn more, check out the interview!

Aly’s story is an all too common example of the price of success in the modern world. Aly was excelling professionally, but in the process his health was falling apart. He was overweight, and had developed type 2 diabetes and sleep apnea. And he was only in his mid-thirties.

He was moving on a dangerous path, and he knew it.

Realizing the peril that he faced, he quit his job and pivoted to an all-encompassing focus on health and fitness. He embraced strength training and lost 70 pounds in the process.

But as he sat on the bench at the gym at 5:00 in the morning, he experienced a moment of clarity. This routine that had restored his health, effective though it had been, was not sustainable. Eventually, he was going to have to return to work, and he would not be able to continue to commit the same amount of time and effort to exercise. How could he maintain the improved health and performance he had gained from training?

As he surveyed the equipment around him, he came up with an idea to remove all of the sources of friction associated with the gym, by packaging all of the exercises he performed into a single machine. And that inspired him to found Tonal.

Tonal is an elegant, wall-mounted device that employs electromagnetism to simulate and control weight, which enables it to replicate the resistance provided by many machines and lifts.

Tonal can deliver 200 pounds of resistance in a device smaller than a flatscreen TV, without having to drive to a gym, rack weights, or even change into workout gear. Better still, it can remove all of the usual guesswork involved with choosing exercises and planning programs. Tonal offers hundreds of guided workouts, presented via a 24” interactive display, and tracks your progress over time.

To learn more about Tonal, and about the future of home exercise training, check out our interview with Aly Orady!

Given its fundamental role in our biology, perhaps it makes sense that specific types of light are connected to our health in some surprising ways, which research is only just starting to elucidate. For example, short-wavelength light (or blue light) has been shown to modulate blood pressure. And some studies have suggested that ultraviolet light might protect against weight gain and cardiovascular disease.

But another form of light exposure, which you’ve probably heard about before, and which we haven’t had the opportunity to address here, until now, is red light therapy.

Like hundreds of technological advances that we take for granted today, the medical application of red light therapy appears to have originated from NASA. Scientists developed red light-emitting diodes (LEDs) to help promote growth in plants on space shuttle missions. From there, red light was investigated for potential medical uses. These LEDs were shown to stimulate energy processes in mitochondria - the organelles from which our cell’s energy is generated. By augmenting mitochondrial function, and enhancing energy production, you would expect cells to be better able to repair and rejuvenate themselves. But is that indeed the case?

In this episode of humanOS Radio, Dan speaks with Michael Hamblin. Dr. Hamblin was (recently retired) Principal Investigator at the Wellman Center for Photomedicine at Massachusetts General Hospital, and an Associate Professor at Harvard Medical School.

There is perhaps no one alive with greater expertise in the health effects of red light therapy and near infrared light than Dr. Hamblin. He is a prolific researcher in photomedicine, having published over 400 peer-reviewed articles on the subject, as well as authored and edited 23 different textbooks.

In this interview, Dr. Hamblin explains:

What photobiomodulation is, and the molecular mechanisms through which it works its magic

What wavelengths and intensities of light are used for physiological effects

How photobiomodulation has been investigated for athletic performance, skin health and rejuvenation, and psychological conditions

When and how to use red light therapy for exercise performance and recovery

How red light functions as a healthy stressor to elicit anti-aging effects

And more!

Yet despite its prevalence, treatments for the condition are lackluster at best. Why is this the case? Perhaps because it remains poorly understood. Insomnia has been known and documented for thousands of years, but it has proven to be difficult to study for a number of reasons. It’s hard to develop good animal models for the condition, it’s difficult to objectively define, and symptoms manifest quite differently in individuals.

In order to address a complex disorder like insomnia, we need to get to the root cause. Generally speaking, it seems clear that the origin lies within the brain. This has compelled some very clever researchers to take snapshots inside the heads of patients with insomnia (via positron emission tomography, or PET), and compare them to normal controls. The results of such studies have been enlightening.

And that brings me to our guest for this episode.

In this episode of humanOS Radio, Dan speaks with Eric Nofzinger. Dr. Nofzinger has spent more than 35 years practicing sleep medicine and studying the neurobiology of insomnia at the University of Pittsburgh School of Medicine.

As a researcher at Pittsburgh, Dr. Nofzinger frequently interacted with patients with insomnia. They would often attribute their inability to sleep to a “racing mind.” If you’ve ever had trouble falling asleep due to incessant rumination, that characterization probably sounds pretty relatable. Furthermore, they would often claim to have hardly slept at all, even when polysomnography showed that they had experienced normal sleep.

He, along with other scientists in the field, suspected that there was a biological basis for these commonly reported complaints. To gain meaningful insight into what was going on, he couldn’t just look at sleep patterns - he needed to look inside the brain. To that end, he started conducting functional imaging studies on patients with insomnia to examine patterns of brain activity and metabolism during sleep.

In one such trial, subjects completed regional cerebral glucose metabolic assessments while awake and while asleep using the FDG PET method. These scans were telling. During normal healthy sleep, there are typically substantial reductions in brain activity, particularly in the frontal cortex. But imaging for individuals with insomnia painted a very different picture. Their brains remained comparatively active during sleep, particularly in the frontal cortex, and they exhibited greater cerebral glucose metabolism during sleep and while awake. So, when these people claimed that their minds were racing throughout the night - when their brains should have been resting - that was actually a remarkably accurate assessment.

These kinds of studies demonstrate that insomnia is, in essence, a disorder of hyperarousal of the brain. With this revelation, what can be done to slow down the racing mind?

Cooling it down.

It has been known for some time that application of a cooling stimulus to the head can lower the brain temperature in the underlying cortex, and in turn reduce brain metabolism. This insight led to the development of Ebb, a sleep therapy unlike any other that has yet been invented. Here’s how it works: the device is comprised of a headband attached to a bedside unit. Cold fluid circulates through the forehead pad from the bedside unit, keeping your forehead at a cool temperature throughout the night. In this way, Nofzinger and his colleagues hope to target the root cause of insomnia, calming the mind and body.

To learn more about Ebb and Dr. Nofzinger’s research, check out the interview!

It has become axiomatic that fruits and vegetables are protective against disease. Humans have intuitively recognized the link between edible plants and health for thousands of years. However, it is only very recently in our history as a species that we have been able to identify these benefits through empirical methods. Over the past decades, countless scientific studies have investigated the relationship between consumption of fruits and vegetables and human health and disease, and compelling evidence has emerged.

But why specifically are plant foods so good for you? What exactly makes them special?

We now believe that biologically active constituents within plants are in large part responsible for their disease-fighting power.

Nicola’s own work has zeroed in on the health-promoting effects of flavonoids, a large class of polyphenolic compounds found in fruits and vegetables. They carry out a variety of important functions in plants, and they affect our bodies as well when we eat them. Just as one example, flavonoids have been shown to enhance bioavailability of nitric oxide, a molecule that regulates vascular tone. Specifically, nitric oxide relaxes the walls of blood vessels, which in turn reduces blood pressure and improves blood flow. With respect to cardiovascular health, you can imagine that this would be a very good thing.

In a recent study, Nicky and her team analyzed data from the Danish Diet, Cancer and Health cohort. This study assessed the diets of 53048 middle-aged Danish residents over the course of up to 23 years. The researchers estimated the flavonoid content of the foods and beverages that these subjects reported consuming, and compared this dietary intake to the medical outcomes and cause of death (if applicable) of the participants.

From this data, a number of important questions could be addressed:

Did flavonoid intake affect mortality, when adjusting for other potential confounders?

What dose of flavonoids is required for benefits to be achieved?

Are certain subclasses of flavonoids responsible for observed benefits?

And do flavonoids have different effects in individuals who drink or smoke?

To hear what they found, and to learn more about dietary flavonoids and their role in health and disease, please check out the interview!

He has conducted grant-funded research from the National Science Foundation and the National Institute of Aging to develop sound environments that can diagnose and treat sleep disorders, improve sleep quality, and optimize daytime alertness. He has also developed several mobile sleep apps, such as the Sonic Sleep Coach, which provides personalized sleep feedback and sounds that are designed to modulate sleep quality.

His current research is focused upon accurately tracking sleep quality through wearable technology. But he doesn’t just want to measure it, he wants to make it better. Dan is particularly interested in using technology to enhance slow wave sleep (also known as deep sleep), which we have addressed previously on this show, through temperature, light, and sound. He delivered an excellent TED talk that explains how stimulating deep sleep can help us learn and consolidate memories, regenerate our tissues, and generally make us healthier and more productive.

In this interview, the two Dans discuss how sleep is studied in a clinical study, how sleep monitoring devices have advanced over the past ten years, potential pitfalls in how these devices are used, ways to augment deep sleep and REM sleep, and much more. To learn about the future of consumer technology and sleep enhancement, check out the podcast!

He and his colleagues recently published a paper examining how light exposure and environmental temperature affect measures of glucose and lipid metabolism in two large population-based European cohorts.

It is well established that exposure to bright light at night is linked to metabolic perturbations. A number of studies have found positive associations between artificial light exposure in the evening and risk of type 2 diabetes. In particular, one experiment from Phyllis Zee’s lab at Northwestern showed that just a single night of blue light exposure during sleep increased insulin resistance in healthy adults.

But what about bright light during the day? Now that’s a different story altogether. Observational evidence suggests that light exposure - particularly sun exposure - may in fact be beneficial for glucose metabolism. For example, a cohort study found that participants who received a lot of sunlight exposure during the day had a 30% lower risk of developing type 2 diabetes, compared to those who didn’t get much sun.

In the study discussed on this show, the researchers collected data from a combined cohort of more than 10,000 healthy middle-aged subjects enrolled in the Oxford Biobank study (OBB) and the Netherlands Epidemiology of Obesity study (NEO). Participants in these studies have provided body composition measurements (weight, body mass index, body fat percentage) as well as bloodwork (fasting glucose, insulin, fasting lipid concentrations, insulin resistance, etc). However, these studies do not assess temperature or light exposure.

To capture the impact of these variables, Sander and his team very cleverly collected data on mean outdoor temperature and hours of bright sunlight (defined as global radiation >120 W/m2) from local weather stations. From this information, they were able to calculate mean outdoor temperature and bright sunlight duration during a 7-day and 30-day period before the date of blood sampling.

Sure enough, increased bright sunlight exposure was found to be associated with lower fasting insulin (−1.27% per extra hour of bright sunlight), lower triglyceride levels (−1.28%), and reduced insulin resistance (HOMA-IR; −1.36%).

After adjustment for bright sunlight, there was no association between outdoor temperature and measures of glucose and lipid metabolism, suggesting that it was indeed the light that was responsible here. But why? What mechanisms mediate this relationship? To find out why Sander thinks bright sunlight might enhance cardiometabolic health, and more about his fascinating work, check out the podcast!

Her research has centered on understanding responses of nerve cells to oxidative stress, and how chemical compounds can modulate these responses to enhance nerve cell function and survival. Her current work is focused on using natural products such as flavonoids to maintain nerve cell function in the presence of toxic insults. Flavonoids are a diverse class of secondary metabolites found in almost all fruits and vegetables. One of the great advantages of these phytochemicals is that they are tiny molecules - small enough to cross the blood-brain barrier. This has been convincingly demonstrated in studies of rodents. For instance, when rats are fed blueberries for ten weeks, and then dissected, anthocyanins from the fruit can actually be found distributed inside the brain!

Maher and her colleagues have been focusing their attention particularly on a few of these flavonoids as potential neuroprotective agents. One of these is fisetin, a flavonoid that is most highly concentrated in strawberries. We have discussed it previously on the show as a possible senolytic agent. Maher and her group have been developing more potent and more bioavailable versions of the flavonoid that might protect nerve cells and even promote learning and memory. Good stuff!

The other phytochemical we’ll be discussing on the show is sterubin. Sterubin is a flavonoid found in Yerba santa, a plant that native tribes in California have long prized for its medicinal properties. When Dr. Maher screened for plant extracts that could act on toxicity pathways relevant to age-associated degenerative disease, sterubin emerged as one with broad protective effects in cell assays.

To learn more about the power of flavonoids and the future of anti-aging research, please check out the interview!

He and his team have begun to investigate the role of advanced glycation end products (also known as AGEs) in the aging process. Advanced glycation end products are compounds that are formed when proteins or lipids become glycated, as a result of being exposed to sugars.

This has been carefully studied and exploited by the food industry for decades, because of its appealing effects on sensory qualities of food. However, it was only recognized comparatively recently that AGEs may impair our health and function over time.

Aptly enough, the formation and accumulation of AGEs is a hallmark of age. AGEs wreak havoc by binding with cell surface receptors and cross-linking with body proteins, altering their structure and function. This produces a range of deleterious effects throughout the body.

So, how can we reduce our exposure to advanced glycation end products in the food that we eat? And how can we control the formation of AGEs inside the body? To learn more, check out the interview below!

In this episode, Dan speaks with an expert on the subject: Judith Campisi, Ph.D., from the Buck Institute of Aging in Marin County, California.