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, we welcome 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, I speak 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, I speak 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, I speak 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, I speak 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!

What do I mean by carbohydrate availability? Well, our storage capacity for carbohydrates is relatively minuscule, compared to fat stores - even on a very lean individual. These stored carbs can be depleted much faster, and several studies suggest that alterations in carbohydrate availability may be carefully monitored by the body.

Importantly, physical activity alters carbohydrate availability by expending muscle glycogen. This may be why exercise has been shown to acutely lower fasting leptin concentrations. Reductions in carbohydrate availability resulting in a drop in leptin levels may explain, for instance, why individuals who utilize carbs faster during exercise seem to be more prone to increased appetite after exercise. But high physical activity levels - and accompanying high physical fitness - produces relevant changes in carbohydrate and fat metabolism, that might actually make them better able to rein in their appetite after a bout of exercise or after a larger-than-normal meal. To learn about these changes, and more about his fascinating hypothesis, check out the podcast!

This area of research has also examined the impact of interrupted work, often in the form of digital notifications, like from email, text, or phone apps. You know how common this is, but you probably don’t realize the full impact. Studies that track employees have revealed that office workers who are interrupted take about 25 minutes to return to whatever task they were working on. And these interruptions take a significant toll on our well-being - research shows that these kinds of disruptions increase stress levels as well as impair productivity.

GUEST

In this show, Dan speaks with Professor Gloria Mark, who is in the department of informatics at UC Irvine, where she studies multi-tasking behavior in information workers, and technology use in disrupted environments. Her work examines how interaction with information technology affects attention, mood, and stress.

When Scott and his team were investigating skin cancer development in mice, they happened to notice that mice receiving ultraviolet radiation gained less weight than counterparts.

These observations inspired Scott and his team to perform a series of experiments examining how regular exposure to physiologically relevant doses of solar ultraviolet radiation (like an amount that you could realistically get on a sunny day) influences weight gain and cardiovascular disease. And the findings were pretty eye-opening.

To learn what they discovered, and more in general about the far-reaching effects of sun exposure on human health, check out this 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!

Dan is also the executive director of the Mindsight Institute, a unique educational organization that provides online learning and in-person lectures that examines the interface of human relationships and basic biological processes, with the goal of cultivating mindsight in individuals, families, and communities.

So what exactly is mindsight? Mindsight is a theoretical construct that is related to theory of mind. However, mindsight goes beyond merely being able to conceive of one’s own mind and that of others. Mindsight refers to the capacity to sense patterns of shared communication of energy and information change within relationships.

It also captures the ability to look inside ourselves, recognizing our own emotions, without being consumed by them. An illustration of this concept, commonly cited by Dr. Siegel, is the subtle difference between “I am sad,” as opposed to “I feel sad.” The latter implies recognition of a feeling you are experiencing in the moment - a state that isn’t permanent, and to which you can control your response.

As you might imagine, mindsight and the intricacies of interpersonal neurobiology are very challenging concepts to understand and research, at least using the tools currently available to biologists and scientists, which is why Dr. Siegel’s work in this area is so valuable. To learn more, check out the interview!

In this episode of humanOS Radio, I speak with Lior Appelbaum. Dr. Appelbaum and colleagues have performed some elegant studies elucidating the molecular mechanisms that underlie sleep, using zebrafish as a model organism.

In a recent study, the team engineered zebrafish larvae to express colorful tags on their chromosomes, making it easy to monitor them. They then followed the activity of the chromosomes in their neurons, as well as DNA damage and repair, and were surprised by what they observed. To learn about their findings, check out the interview!

In his study, Miller and his team randomly assigned 53 participants to consume either placebo or metformin for 12-weeks, while completing a supervised aerobic exercise program. This exercise regimen elicited measurable improvements in blood sugar control, insulin sensitivity, and aerobic fitness for the volunteers, as you would obviously expect.

But when the groups were compared, some meaningful - and troubling - differences emerged, suggesting that metformin was counteracting some of the benefits associated with exercise. Check out the interview to learn more!

Thryve helps consumers test and learn about their own microbiota by providing at-home microbiome test kits. But here's what sets Thryve apart: they don't just give you information, they also endeavor to provide solutions. Thryve offers monthly subscriptions of personalized probiotics to customers, which are formulated based on their microbiome and their individual health goals. To learn more about Thryve, and about the exciting future of microbiome testing and probiotics, please check out the interview!

So why does this happen? As with most things in biology, there are definitely multiple factors at work here. But one likely reason is a failure of quality control. As we age, mitochondrial autophagy (aka mitophagy) declines, and our body starts to accumulate broken and dysfunctional mitochondria. This becomes most obvious in tissues that consume a lot of energy, like skeletal muscle. Hence, mitochondrial dysfunction is linked to poor muscular strength in older people. If we could find a way to ramp up mitophagy, perhaps we could retain excellent mitochondrial function throughout our golden years.

In this episode of humanOS Radio, we welcome Dr. Davide D’Amico to the show. Davide is a research scientist in the field of metabolism and aging. He was previously a post-doc at the Auwerx Laboratory of Integrative Systems Physiology at the École Polytechnique Fédérale de Lausanne (EPFL), where he investigated the role of mitochondrial function in health, disease, and the aging process.

In this interview, we discuss a recently published study from his team, which revealed one of the molecular mechanisms through which defective mitochondria accumulate in cells. Additionally, Davide is a scientific project manager at Amazentis, where he is investigating a naturally derived bioactive from pomegranate, that has been shown in a new clinical trial to reverse age-related decline in mitochondrial function in the muscles of older people. Please check out the interview to learn more about this exciting research!

In this episode of humanOS Radio, I speak with Ken Raj. Ken is a Senior Scientific Group Leader at Public Health London, and has worked extensively with Dr. Steve Horvath of UCLA in developing and interpreting genomic biomarkers of aging. They are best known for developing the “epigenetic clock,” a tool that predicts life expectancy by examining age-related changes to DNA methylation, then using that information to calculate biological age in relation to chronological age. The epigenetic clock is able to predict life expectancy with remarkable accuracy, with a margin of error of plus or minus three years.

In this podcast, we discuss:

-How the epigenetic clock uses DNA methylation to compare biological to chronological age. -Whether DNA methylation changes are the “drivers” or the “passengers” of biological aging, and how direct a role they play in the aging process. -Whether or not epigenetic changes can be passed down from generation to generation. -Whether or not someone with a biological age greater than their chronological age is more likely to develop certain pathologies. -On the other hand, whether having a younger biological age than chronological age means greater health and a longer life. -What diet and lifestyle factors have been researched to show an impact on epigenetic aging. -Whether or not epigenetic drugs have the ability to modify this clock and slow aging. -The potential for extracting the exact mechanisms through which things like exercise and certain dietary interventions slow down epigenetic aging. -If the epigenetic clock can be used for earlier diagnosis of such age-related conditions as cancer, diabetes and neurodegenerative diseases, leading to better outcomes.

To learn more, check out the blog!

Dr. Newman’s research focuses predominantly on ketone bodies - molecules produced in the liver when glucose is scarce, either due to restricted intake or prolonged physical activity. So we tend to think of them primarily as an alternative source of fuel, particularly in the context of a low carb diet. However, they are also intriguing with respect to aging, because of how they function as molecular signals, and how they influence gene expression.

You might think, intuitively, that the process of natural selection would gradually eliminate senescence. Aging increases mortality, and organisms that experience impaired function and ultimately die would not be able to produce as many offspring as one that was able to live (and to reproduce) indefinitely, or at least for a much longer timespan. So, you would assume that this would result in selection for organisms that live much longer, generate more offspring, and ultimately the causes of age-related deterioration would fade from the genome. Yet aging is very commonly observed. Why is that?

Natural selection is strongest in early life. This makes sense - the natural environment is full of predators, disease, and other perils that often kill organisms when they are young and vulnerable. Consequently, genes and pathways that enhance survival and reproduction in early life are likely to be favored - even if they come at the cost of problems later in life, when selection is comparatively weak. But is aging inevitable? Can it be slowed, or postponed, or stopped altogether?

In this installment of humanOS, Dan talks with Michael Rose. Dr. Rose is a Distinguished Professor of Ecology and Evolutionary Biology at UC Irvine. He is a prolific biologist whose research into the evolution of aging has effectively transformed that field. Rose’s laboratory has been testing the theory of antagonistic pleiotropy for nearly forty years, through artificial selection experiments in fruit flies.

In what was perhaps his most famous experiment, Rose allowed flies to only reproduce successfully if they laid their eggs late in life. He discarded the eggs of any flies that laid eggs before they reached fifty years of age. Over a few generations, this population of flies evolved longer lifespans. Why might this be? Remember that natural selection is strongest early in life, and becomes weak later on. In theory, if adults reproduce when they are older, natural selection is apt to favor genes that enhance resilience (and reproduction) later into the lifespan.

Dr. Rose's research into aging has also drawn him to some interesting (and possibly controversial) notions about evolutionary changes in the human diet, and how our age may influence how adapted we are to modern agricultural foods. To learn what that means, and its potential implications, check out the interview!

Research on preindustrial societies has consistently shown that these people have exemplary metabolic health. And when we consider that modern humans are succumbing to chronic diseases at an alarming rate, we clearly have much to learn from preindustrial people.

In this episode of humanOS Radio, Greg Potter speaks with Professor Herman Pontzer about what Herman has learned from his research on hunter-gatherers. Herman's findings led him to develop the counterintuitive hypothesis that how physically active we are each day may scarcely affect how many calories we burn…

… no, I’m not kidding.

As he explains in the podcast, however, this hypothesis in no way discounts the importance of being physically active – far from it!

Tune in for more on Herman’s fascinating research on physical activity, diet, and more.

In the last few years, numerous wearable devices that claim to monitor how we’re responding to stress have become available, and most of these measure either heart rate variability (HRV) or pulse rate variability. In this episode of humanOS Radio, Professor Phyllis Stein explains what you need to know about HRV, including what it is, why people measure it, and whether you should measure your own HRV.

In addition, food is arguably the most powerful and primal motivator for animals, ourselves included. And every single one of us has cultivated deep-seated dietary preferences, often established in our formative years. In other words, we are all biased, to varying degrees. It's hard for us to view our favorite foods in an entirely objective way - even when they are slowly making us sick. To further complicate matters, nutrition is very difficult to research rigorously, and studies are often rife with confounders and apparently contradictory results.

The controversial nature of nutrition science was on full display this Tuesday, when Stephan Guyenet and Gary Taubes appeared together on the Joe Rogan Experience podcast to debate the causes of obesity and type 2 diabetes. Gary and Stephan have very different points of view on this subject, informed by rather different approaches to scientific literature. But as is often the case in debates, there was much that Stephan wanted to say but didn’t get an opportunity to address. That’s why we have welcomed him back to humanOS Radio, to reflect upon his experience on Joe Rogan’s podcast and to further elucidate the causes of obesity and insulin resistance. Click below to check out the interview!

In this interview James shares many useful insights regarding how to perform better at work. This podcast also includes a discussion on:

- What “knowledge work” is

-What traits and behaviors differentiate the successful from those who fall by the wayside

-The importance of understanding our daily rhythms in cognitive function

-How planning sports training has influenced the way James helps people perform better at work

-The idea of “cognitive gears”, and why many of us would benefit from clearer demarcations between focused work and recovery

-The reciprocal relationship between physical endurance and mental endurance

-Physical activity for workers

-The importance of mood and learning in workplace performance

-How to start the day on the right foot

-How to prepare for restorative sleep at night (note that I've written about caffeine, alcohol, light exposure, and temperature previously)

-How to become better at public speaking

But what if aging were actually a modifiable risk factor?

Your chronological age, meaning the length of time that you have been alive, obviously cannot be changed. But we know that biological aging can vary significantly, even among individuals who are of similar chronological age. If we can better understand the fundamental mechanisms that underlie biological aging, we might be able to devise interventions that could prevent or delay age-related diseases.

One of the relevant processes is cellular senescence. Cellular senescence is a phenomenon through which normal cells irreversibly cease to divide in response to genomic damage. Senescent cells accumulate in the body as we get older, and they actually do a lot of bad stuff in the body. Senescent cells secrete pro-inflammatory factors, like cytokines, which induces a state of chronic low-grade inflammation. But it gets even worse. These senescent cells can also drive other healthy neighboring cells into senescence. So senescent cells are basically microscopic zombies!

This has driven interest in identifying senolytics - compounds that can selectively kill senescent cells (while leaving normal cells alone).

In this episode of humanOS Radio, I talk to Paul Robbins. Paul is the principal investigator at the Robbins Lab at Scripps Research Institute. Notably, his lab has been screening for drugs that can safely and effectively clear out senescent cells.

This research has produced some remarkable results in animal models. For example, he and colleagues found that older mice that were given senolytics became faster and stronger, and experienced a 36% increased median post-treatment lifespan, compared to a control group. Wow!

That’s just a tiny snapshot of this incredibly important work. To learn more, please check out the interview!

Most of us have a list of things we would like to change. Maybe you’d like to lose thirty pounds, or be able to do fifty pushups, or run a marathon. But each of these comes with a long list of associated behaviors - many of which aren’t intrinsically rewarding - that are required to achieve and maintain these goals. It’s no wonder the statistics on weight loss are so underwhelming.

On this episode of humanOS Radio, I talk with James Clear. James is an author and entrepreneur who is focused on habits, decision-making, and continuous improvement. His work has appeared in the New York Times, Time magazine, and other major media outlets.

In his latest book, “Atomic Habits,” James draws upon a wide array of evidence from psychology, biology, and cognitive neuroscience to construct a guide for building and reinforcing good habits and abolishing bad habits.

So what are habits? James defines habits as behaviors that are repeated enough times to be nearly automatic. This means they are not demanding cognitive effort or willpower. Like brushing your teeth, or heading to the gym at 5:00pm every day, or eating a smoothie every day for breakfast. These automatic processes, which are mostly mundane things that we take for granted, are actually foundational to all of our goals.

The problem, of course, is that we generally don’t see the immediate payoff for any of these behaviors. You don’t drop twenty pounds just switching from regular to diet soda one time. It is only after you’ve committed to these behaviors for a while - after your efforts have compounded - that we start to see the difference. That is why we need to develop a system to assess our current habits and build better ones. This is where “Atomic Habits” comes into play.

Moreover, sleep also seems to be nearly universal in the animal kingdom. Indeed, we have yet to identify an animal that clearly does not sleep at all, or even one that can forego sleep without experiencing physiological consequences.

All of this, taken together, unambiguously shows that sleep is extremely important. And this makes it all the more remarkable that the actual purpose of sleep remains elusive.

One idea is that sleep may function as an antioxidant for the brain, protecting neural tissue from the ravages of oxidative stress. This hypothesis largely fell out of favor, but researchers have recently started to revisit this compelling notion.

In this episode of humanOS Radio, I talk to Mimi Shirasu-Hiza. Mimi is an associate professor of Genetics and Development at Columbia University. Her lab uses circadian mutants of fruit flies to unveil the molecular mechanisms that underlie circadian-regulated physiology. Mimi and her colleagues hypothesized that fruit flies with various genetic mutations that reduce their sleep might share a common physiological defect due to that sleep loss, but independent of the specific mechanisms driving their reduced sleep. And if they could find such a defect, that might reveal the core function of sleep in animals (including us).

Through an elegant series of experiments, Mimi and her team did indeed uncover a shared defect, which points to a possible purpose of sleep in fruit flies and perhaps in humans. Check out the interview to find out what they discovered and what it might mean for us!

Today on humanOS Radio, I talk to Kristine Wilckens. Kristine is an assistant professor in the Sleep and Chronobiology Center in the Department of Psychiatry at the University of Pittsburgh. Her research has focused on how sleep structure can be altered to enhance cognitive function.

In this interview, we review the role of slow wave sleep in learning and memory consolidation, and the kinds of activities that have been demonstrated to promote slow wave sleep. Many of these techniques - like heat exposure - are things that you can experiment with yourself right now. Check out the interview to learn more!

Professor Hay and his team have done work showing that when they stimulate mitophagy – a process in which mutant mitochondria are selected, tagged, and then shipped to organelles that break them down - they might allow healthy mitochondria to substitute in their place, rejuvenating cellular function, a finding that could have profound implications for those of us seeking to ward off aging.

But what exactly is REM sleep actually for? In this show, I speak with Professor John Peever, Director of the Centre for Biology Timing and Cognition at the University of Toronto. Professor Peever’s research focuses on how the brain regulates wakefulness and sleep, and our discussion focuses on REM sleep.

This is a very scary proposition and this problem is not likely to go away on its own. We need new ways to control bacterial infections and we need them fast. And that brings us to my guest today.

In this episode of humanOS Radio, I speak with Paul Garofolo. Paul is the CEO of Locus Biosciences, a biotech company that is developing a novel class of antimicrobials that take advantage of the CRISPR-Cas system. If this pans out, it would offer a viable alternative to conventional antibiotics, and would presumably be less subject to the known mechanisms of drug resistance. Secondly, this method could be targeted to specific pathogenic bacteria, thus leaving your friendly bugs alone. This seems like a win-win that is both lifesaving and health promoting, potentially (depending on the context).

In this episode of humanOS Radio, I talk to Peter Light. Dr. Light is a pharmacologist and a leader in the field of cellular electrical activity. He is chief investigator at the Light Lab at the University of Alberta, and director of the U of A's Alberta Diabetes Institute.

He and his research team discovered - largely by accident - that chronic exposure to blue light causes human fat cells to shrink, store less lipid, and alter their function in other ways that are likely relevant to metabolic health. This suggests that subcutaneous fat might be a sort of peripheral biological clock, and raises all sorts of intriguing questions. Could repeated exposure to blue light serve as a protective mechanism against insulin resistance, chronic systemic inflammation, or even obesity? Listen to the interview below to learn more!

This is most evident in the muscles and bones, but neuroimaging has revealed that this occurs in the brain as well. The aging brain becomes less specialized than that of younger counterparts. We see increased secondary activation in areas of the brain that are not typically involved, possibly as a way to compensate for poorer signal transmission.  

One intervention that we know helps to restore complexity and plasticity is exercise. No big surprise there. Another, oddly enough, is beetroot juice.

In today’s episode of humanOS Radio, I talk to Dr. Jonathan Burdette. Dr. Burdette is a neuroradiologist and researcher at Wake Forest School of Medicine, who uses advanced MR imaging techniques to study the brain as a complex and interconnected network.

Recently, he and his team designed a clinical trial to investigate whether beetroot juice - in combination with an exercise regimen - could enhance neuroplasticity and improve brain function in measurable ways.

In his recent study in Nature, his team examined variants of the genes that code for fatty acid desaturase (FADS).  This mutation consists of an insertion or a deletion of some DNA base pairs, which affects the expression of the fatty acid desaturase genes, which could then influence who well or poorly we create essential fatty acids from plant matter, which could subsequently influence what diet might be best for you. And good news, you can now get this test done to determine if you are the paleo type or farmer type in your FADS gene variant.

However, recent brain studies have revealed that the aging brain changes in ways that makes sleep less restorative. This suggests that the real reason why older adults get less sleep than their younger counterparts is because they are less capable of generating the sleep that they really need.

In this episode of humanOS Radio, I talk with Bryce Mander, a postdoctoral fellow in the Matthew Walker Sleep and Neuroimaging Lab at UC Berkeley. Bryce and colleagues recently wrote a review that explores how sleep changes as we grow older, and the potential long-term implications of these alterations. Perhaps most alarming, research has shown that a lack of deep sleep is associated with higher levels of amyloid beta, which are the toxic misfolded proteins that accumulate in the brains of those afflicted with Alzheimer’s disease.

This raises a number of interesting questions. If we could test for sleep disruption, could we determine who is susceptible to developing Alzheimer’s disease soon enough to intervene? And could we find ways to enhance slow wave oscillations as people grow older, so that we can enjoy high-quality restorative sleep our whole lives? Listen here to learn more!

Her research investigates how disruptions to circadian rhythms may affect physiological functions, and ultimately could make individuals more vulnerable to disease.

This affects all of us, to varying degrees, and perhaps in ways that we don't even realize. Listen hear as we discuss her fascinating work.

In this episode of humanOS Radio, I spoke with Daniel Schmachtenberger. Daniel is a social engineer, an evolutionary philosopher, and he works with a group called Neurohacker Collective, who is dedicated to optimizing human performance.

In this interview, we discuss current research investigating human cognitive enhancement and nootropics. We also talk specifically about the cognitive enhancer Qualia, which is a carefully formulated nootropic stack Daniel helped design.

In this interview with Jari Laukkanen, MD, Ph.D., Head of the Cardiology Department at the University of Eastern Finland, we explore his fascinating findings looking at the difference in brain health in men who frequently take a dry hot sauna compared to those who sauna less frequently. If these results came from a new pill, it would be called a miracle.

But why does this happen? Is it the tryptophan in the turkey? Is it from too many carbs? What you eat, how much you eat, and when you eat it all play a role. Consequently, there has been some doubt as to whether the “food coma” is even a real thing.

But recently, some clever researchers identified a good model organism for studying this phenomenon - the fruit fly. And through studying the behavior of Drosophila, we now better understand what causes a food coma, and perhaps why it occurs.

In the latest episode of humanOS Radio, I interview Keith Murphy of the Scripps Research Institute. He and his colleagues have been researching the so-called food coma, and have found some substantive evidence for this phenomenon. Listen here to find out more about his study - and some reasons why the food coma might be happening.

In this latest episode of humanOS radio, I interview Emma Templeton from Thalia Wheatley's lab at Dartmouth and Michael Stanton, Assistant Professor, Department of Nursing & Health Sciences, California State University, East Bay. Recently, they published a study in the journal, PLoS ONE, that elegantly tests the influence of social norms on the perceived healthfulness of food and also eating behavior. Listen here to hear more.

In this episode, Stephan and I discuss genetics, stress, food palatability and reinforcement, and other important factors to shed light onto the mechanics behind weight regulation.

In this episode of humanOS Radio, I speak with Drs. Michael and Irina Conboy of the Department of Engineering at UC Berkeley. Their lab investigates the process of tissue repair throughout the body, and is trying to determine why damaged tissue is not productively repaired as the body ages.

The guests of this episode of humanOS Radio are Kelly and Juliet Starrett. Kelly is a Doctor of Physical Therapy and the author of the books: Deskbound, Supple Leopard, and Ready to Run. Juliet has a history as a competitive athlete, rowing at UC Berkeley and paddling for the US Women's Whitewater Team from 1997-2000. Together, they founded San Francisco CrossFit in 2005 (one of the first 50 CrossFit Affiliates ever), they run the healthy movement website called Mobility WOD, and most recently, they started StandUpKids.org the mission of which is to put standing desks in every public school in America. I'm also honored to be on the Board of Directors, which I mentioned in this previous post, to help this great organization achieve its mission.