humanOS Radio

In this episode of the humanOS Radio podcast, we welcome Hannah Went, a visionary in the realm of longevity and disruptive health technologies. With a lifelong passion for breakthrough innovations that improve the human condition, Hannah's journey began at the University of Kentucky, where she earned her degree in Biology. Her early research internships in cell signaling and cell biology laid the groundwork for her career in integrative medicine. 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.

Taurine is often associated with energy drinks and pre-workout supplements, although ironically, it is not a stimulant and may have the opposite effect. While taurine is not considered an essential nutrient for adults, as our bodies can produce it from other amino acids, recent evidence suggests that it offers numerous health benefits. These include improved blood sugar regulation, reduced oxidative stress, and lower blood pressure. 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. 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.

Ralph Waldo Emerson once wrote, "The eyes indicate the antiquity of the soul." But we now know that your eyes may also provide a remarkably accurate measure of the true age of your body. 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!

In our previous interview with Dr. Kapahi, we discussed his work examining how advanced glycation end products (also known as AGEs) drive the aging process. Since we last spoke, Pankaj has been hard at work trying to identify compounds that can rein in the deleterious impact of AGEs, primarily by lowering levels of methylglyoxal. Methylglyoxal is formed as a side product of the breakdown of sugars, and is involved with the formation of AGEs, so it is a logical molecular target here. In his screening process of over 800 compounds, he managed to find five compounds which, when combined, had synergistic protective effects against methylglyoxal toxicity. 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.

On this episode of humanOS Radio, I speak with Lynda Frassetto. Lynda is a Professor Emeritus of Medicine in the Division of Nephrology at UCSF. During her research career, she and her colleagues investigated regulation of acid-base balance in both healthy and older people, as well as dietary influences on acid-base balance.  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!

On this episode of humanOS Radio, Dan speaks with Paul Spagnuolo. Dr. Spagnuolo has a PhD in Applied Health Sciences from the University of Waterloo, and is currently a Professor at the Department of Food Science at the University of Guelph in Ontario Canada. His lab has been focused on identifying and developing nutraceuticals as novel therapeutic agents, and figuring out the molecular and cellular mechanisms through which these food-derived bioactive compounds influence cell biology. To that end, the Spagnuolo lab has created a unique, in-house nutraceutical library that is conducive for high-throughput screening. This is useful because it allows the lab to efficiently search for compounds with potent and selective toxicity against cancer cells. When screening this natural health product library for potential therapeutics, they discovered avocatin B, a mixture of polyhydroxylated fatty alcohols that is found exclusively in avocados. Avocatin B is a potent inhibitor of fatty acid oxidation (FAO), which makes it a promising candidate as a drug to block or delay some of the cellular processes that lead to insulin resistance and diabetes. In theory, reducing FAO in skeletal muscle and in pancreatic beta cells would force cells to burn glucose instead of fatty acids. This boost in glucose oxidation would be expected to lower blood sugar levels and restore insulin sensitivity. But of course, the only way to know whether it actually works is to put it to the test. Paul and his team wanted to explore whether this avocado compound could indeed help with metabolic syndrome. To that end, they recently performed a series of experiments testing avocatin B in rodent models of obesity and insulin resistance, as well as a randomized controlled clinical trial in humans. To learn what they found, check out the interview!

On this episode of humanOS Radio, Dan speaks with Brad Dieter. Brad has a PhD in Exercise Physiology from the University of Idaho, and did further training in biomedical research examining how metabolism and inflammation regulate molecular mechanisms of disease. He is a scientist, a coach, an entrepreneur, a writer, and a speaker, so he wears a lot of different hats. 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!

Within our gut resides a vast ecosystem that guides countless facets of health and performance. Emerging research shows that your gut microbiota may impact many different and seemingly unrelated aspects of health and bodily function, including appetite and body weight regulation, lifespan, mood, cognition, and even athletic performance. 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!

In this episode of humanOS Radio, Dan speaks with Jennifer Goldschmied. Jennifer has a Ph.D. in Clinical Psychology from the University of Michigan, and is currently faculty at the University of Pennsylvania. 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!

The market for dietary supplements to enhance sports performance has exploded in recent years. In fact, you may have tried some of these supplements yourself to improve your workouts. 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!

When you hear the word superfood, what do you think of? Probably kale. Goji berries. Green tea. Turmeric. Countless others. 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 this episode of humanOS Radio, Dan welcomes Dr. Jamie Zeitzer back to the show. Jamie is an Assistant Professor in the Department of Psychiatry and Behavioral Sciences at Stanford University, as well as at the VA Aging Clinical Research Center at Stanford. 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!

In this episode of humanOS Radio, Dan speaks with Julie Andersen. Julie has a Ph.D in neurobiological chemistry from UCLA, and subsequently did her post-doctoral fellowship in the department of neurology at Harvard. 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!

On the surface, sleep looks like a colossal waste of time. Think about it. We spend about a third of our lives lying down with our eyes closed...basically doing nothing! 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!

For much of our history as a species, the threat of chronic food shortage and malnutrition has loomed over us. 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!

Have you ever wondered what your great-great-grandparents would think of the world today - and how we live - if they were transported here via a time machine? 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!

Why do so many people struggle to stick to a healthy lifestyle? 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!

All of us have heard the aphorism, “Let food be thy medicine, and medicine be thy food.” This maxim, of course, is usually attributed to ancient Greek physician Hippocrates. 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!

On this episode of humanOS Radio, Dan welcomes Aly Orady - founder and CEO of Tonal - to the show. 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!

Light is essential to life as we know it. Plants rely upon sunlight to generate chemical energy, which is stored in their tissues and fuels various life processes. In turn, animals like us convert the energy from the food that we eat into mechanical energy. 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!

Insomnia is a uniquely vexing medical problem. It is the most common sleep-related issue, thought to affect around 10-40% of the population in the US. So it is a challenge that affects a whole lot of us. 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!

On this episode of humanOS Radio, Dan welcomes Nicola Bondonno to the show. Her research has been examining the effects of bioactive compounds occurring naturally in plant-based foods and beverages, and how they are linked to the cardiovascular health benefits associated with a plant-rich diet. 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!

On this episode of humanOS Radio, Dan welcomes Daniel Gartenberg to the show. Dan has dedicated his life to helping people sleep better (a calling that we here at humanOS can certainly relate to). Daniel has a Ph.D in Human Factors and Applied Cognition from George Mason University, and is an adjunct assistant professor at Penn State University. 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!

In this episode of humanOS Radio, Dan speaks with Sander Kooijman. Sander is a post-doctoral researcher at Leiden University Medical Center, where he is investigating brown adipose tissue activation as a therapeutic target to attenuate obesity, type 2 diabetes, and atherosclerosis in humans. 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!

In this episode of humanOS Radio, Dan speaks with Pamela Maher. Dr. Maher has a Ph.D. in biochemistry from the University of British Columbia. She was formerly an associate professor at The Scripps Research Institute in La Jolla. In 2004, she moved to her current position as a research scientist at the Salk Institute for Biological Studies. 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!

In this episode of humanOS Radio, Dan speaks with Javier Gonzalez. Dr. Gonzalez is a professor at the Department for Health at the University of Bath in the UK. He and his colleagues recently published a hypothesis suggesting that carbohydrate availability plays a key role in the regulation of energy balance, and explains both why exercise increases hunger and (paradoxically) why people who are highly active exhibit better appetite regulation. 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!

We live in an era of unprecedented access to information. Technology has endowed us with the ability to immediately retrieve whatever we want to see or whatever we want to read, just by tapping on a screen a few times. Perhaps even more importantly, we have never had so much immediate access to one another, even when we are very far away. In turn, other people - as well as our devices - have the ability to reach out to us and seize our attention, literally 24 hours per day, seven days per week. But how does this relationship with technology affect our brains? Researchers are examining the impact of digital tools on how we think and perform, and the results are not entirely rosy. Much of this research has investigated what we commonly refer to as “multi-tasking.” You already know this implicitly: when you are rapidly switching between two different activities, typically your performance on both suffers. 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. 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.

In this episode of humanOS Radio, Dan speaks with Scott Byrne. Scott is a professor at the University of Sydney School of Medicine. He is a cellular immunologist who is studying how the ultraviolet part of the solar spectrum activates regulatory pathways that result in immune suppression and tolerance. 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!

On this episode of humanOS Radio, Dan welcomes Pankaj Kapahi to the show. Pankaj is a professor at the Buck Institute, an independent biomedical research institute that is devoted solely to research on aging. 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!

On this episode of humanOS Radio, Dan speaks with Dan Siegel. Dr. Siegel is a clinical professor of psychiatry at the UCLA School of Medicine, and is the founding co-director of the Mindful Awareness Research Center at UCLA. He is a pioneer in a field known as interpersonal neurobiology (sometimes referred to as relational neuroscience). Interpersonal neurobiology characterizes human development and function as a product of interactions between the body, the mind, and relationships with one another. 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!

Why do we sleep? This is a question that has bedeviled researchers for decades. But we think one major reason may be to facilitate DNA repair. In this episode of humanOS Radio, Dan speaks 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!

On this episode of humanOS Radio, Dan welcomes Ben Miller to the show. Ben is a principal investigator in the aging and metabolism research program at the Oklahoma Medical Research Foundation. 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!

On this episode of humanOS Radio, Dan speaks with Richard Lin. Like all too many of us, Richard became personally invested in his health when he developed a problem that failed to respond to conventional medical interventions. He eventually realized that a disruption in the gut microbiota was the likely cause of his illness. This inspired him to start Thryve Inside. 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!

We associate getting older with a loss of energy. On the molecular level, this is quite literally true, because one of the hallmarks of aging is mitochondrial dysfunction. Mitochondria are often referred to as “the powerhouse of the cell,” because they convert nutrients from the food we eat into usable energy, in the form of ATP. But as we age, mitochondria become less effective at generating the energy we need for various chemical processes. 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, Dan welcomes 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!

We tend to think of age in terms of the number of years we have been alive - meaning our chronological age. But the year that you were born is not necessarily an accurate measure of your health or your life expectancy. We are coming to realize that a better predictor is your biological age - and that can be quite different from your chronological age. So how do you learn your biological age? And what can you do with this information? In this episode of humanOS Radio, Dan speaks 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!

In this episode of humanOS Radio, Dan speaks with John Newman. Dr. Newman is a geriatrician (a physician who specializes in the care of older people) at UCSF, as well as a professor at the Buck Institute for Research on Aging. He is chief investigator at the Newman Lab, where he is exploring ways to harness metabolic signals to promote health and resilience, particularly in older adults. 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.

Why do we age? The fundamental causes of aging at the molecular level are relatively well established. But the question of why aging happens in the first place is a more challenging one, one which has bedeviled evolutionary biologists and philosophers for years. 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!

For the vast majority of human history, our species lived hunter-gatherer lifestyles. We can therefore learn much about how humans probably once lived by studying preindustrial societies. 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.

Do smartphones really affect the timing and quality of your sleep? In this episode of humanOS Radio, Dan speaks with Dr. Jeanne Duffy from Harvard Medical School on her most recent research investigating this question.

Stress is something we all experience all too frequently. The effects of different stressors accumulate, and when the resultant load is excessive, we are at increased risk of a range of diseases. So, to avoid the amount of stress we experience exceeding our bodies' capacities to cope, it would be useful to have a way to monitor how we're responding to stressors. 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.

Nutrition is perhaps the most emotionally charged of all of the applied sciences. It's not hard to see why. For one thing, all of us eat, meaning that every single one of us is personally invested in this topic, and we interact with it all the time. We all develop a sense of expertise, in a way that we might not for something a bit more removed from our daily life, like robotics or civil engineering. 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 podcast, Greg Potter speaks with James Hewitt, who has a particular interest in how people can achieve sustainable high performance. In addition to his role as Chief Innovation Officer at Hintsa Performance, James is doing a PhD at Loughborough University, where his research focuses on how workers' lifestyle and work patterns influence their wellbeing and performance. 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

Brain injury is more pervasive and problematic than many people think. Every day, about 150 people die from traumatic brain injury-related deaths in the US alone, and whether you participate in a contact sport, work in the military, or simply travel on roads, you may at some point suffer the kind of event that incites brain injury. The problem is that brain injury is associated with numerous negative health consequences, including mental health issues and diseases such as Parkinson's. Fortunately, there are things that we can do to help us protect against the negative consequences of brain injury. There are good reasons to think that we may benefit from using exogenous ketones for brain injury, for example. This episode of humanOS Radio explores these subjects with Dr. Tommy Wood.

Whether you want to look great at the beach, perform better at sports, or ward off disease, it's important to optimize your protein intake. This brings us to the latest episode of humanOS Radio, in which Dan speaks with Professor Stu Phillips from McMaster University. Tune in to find out more!

Aging is arguably the leading risk factor for chronic diseases in the modern world. We have historically thought of aging as an inexorable decline of function, driven by the passage of time - something that we simply have to accept, and that cannot be changed. 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, Dan talks 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!

Why is it so hard for us to make healthy lifestyle changes - even when we have the knowledge to do better? 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, Dan speaks 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.

Why do we need to sleep? Part of what makes sleep so fascinating, as a field of research, is that it is such an enigma. Sleep is a profoundly vulnerable state, leaving us at the mercy of predators and the environment, and unable to defend ourselves or our possessions. It's also largely unproductive. Yet we spend about a third of our life in slumber. 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, Dan talks 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!

All of us know that lack of sleep impairs cognitive performance. But we are now realizing that sleep quality, and how long that you spend in deeper restorative sleep, also plays an important role in brain function. Today on humanOS Radio, Dan talks 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!

The subject of alcohol and health is complex. There is evidence that alcohol can be health-promoting, but more recent evidence has suggested it isn't healthy for humans in any amount. The ancient Greeks only drank their wine diluted. They believed that only barbarians would drink unmixed or undiluted wine as it would bring out a type of behavior that would cause mayhem. In this episode, Dan speaks with Todd White, CEO of Dry Farm Wines, to discuss and compare the differences between conventional wines with natural wines - which tend to be lower in alcohol, calories, sugar, and additives, while higher in phytochemicals like polyphenols - as well as a discussion of the effects these different types of wine on health. Be sure to check blog.humanOS.me for a longer discussion of alcohol and health.

About 40% of people worldwide will get lower back pain at some point in life, and on any given day roughly 12% of adults are experiencing lower back pain. This crippling condition strongly influences quality of life, often affecting relationships with loved ones, impairing performance at work, and leading to substantial costs – not only healthcare ones but also expenses due to absenteeism and so on. This episode features Dr. Stuart McGill. Dr. McGill is a professor emeritus at the University of Waterloo. He has published more than 240 peer-reviewed scientific articles in which he used an array of methods to explore the causes of back pain, the most effective ways to rehabilitate back pain, and strategies to optimize athletic performance while sparing people's spines. Dr. McGill continues to help numerous people overcome back pain and has worked with a spectrum of people spanning Olympic medalists, members of the special forces, the government, and the general population too.

Perhaps you want to feel great about how you look at the beach. Maybe you play a sport in which it's important to be powerful and strong relative to your weight. Or you might simply be interested in continuing to function well as years pass by. Whatever your goals are, you should be interested in the mass and quality of your muscle tissue. In this episode of humanOS Radio Dan speaks with Dr. Keith Baar, Professor in Residence in the Department of Physiology and Membrane Biology in the UC Davis School of Medicine, about this important subject, addressing topics such as how to exercise and eat to optimize muscle mass and function across the lifespan.