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Flavonoids and Brain Health. Podcast with Dr. Pamela Maher

More than 2000 years ago, the Roman poet Virgil wrote, “Time robs us of all, even of memory.” Humans have long recognized the insidious toll that aging takes on the body – including the brain. But it is only very recently in our history as a species that we have been able to conceive of plausible ways to halt or even reverse it. As we gradually unveil the fundamental mechanisms of biological aging, we are starting to develop interventions that directly combat the diseases emanating from this process.

And there is no target of this research that is more important than the brain. Your brain, after all, is what truly makes you who you are. The threat of losing our memories, our personality, and our connections to one another is perhaps more frightening than anything else. It is also a daunting challenge. Modern medicine has enabled us to repair or even wholly replace many other parts of the body, including vital organs. But how do you regrow or replace an aging mind?

Indeed, research into medical interventions to address problems associated with aging in the brain has been particularly disappointing. Just as one example, pharmaceutical drugs designed to treat Alzheimer’s disease have the highest failure rate of any disease area (99.6%). Why is this? One reason, perhaps, is that the brain is terribly complicated, and a constellation of different factors have been implicated in age-related decline in the function of the brain. Consequently, using a drug to target a single aspect of the disease process is unlikely to be completely successful. To have any chance for solving this monumental problem, it is thought that we will need to identify molecules that have multiple biological activities and ameliorate multiple aspects of aging. And that brings me to our guest for today.

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, and currently works 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. 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!


Carbohydrate Availability, Energy Balance, and Exercise. Podcast with Dr. Javier Gonzalez.

Why is losing weight – and keeping weight off – such a puzzle? At the individual level, the problem seems to be quite simple: it is chronic positive energy balance.

Simple, perhaps, but not easy. Changes in energy intake or energy expenditure can activate ancient feedback mechanisms that have evolved to preserve energy balance. And unfortunately for us, this system doesn’t seem to be biased toward supporting our beach body goals – it is adapted for survival.

This is one reason why exercise interventions often do not result in as much weight loss as would be predicted based on the projected energy expenditure produced by the activity. Changes in hormones, which are elicited by the energy deficient, cause hunger to ramp up. Consequently, many people who participate in structured exercise interventions wind up eating more food to partially or wholly compensate for the calories burned by that activity.

So, does this mean that exercise is a futile endeavor for managing weight? Actually…no. Not at all.

Research has shown that people who are highly physically active tend to be leaner than counterparts with a sedentary lifestyle. And oddly enough, it may be due to improved appetite regulation. For example, when scientists present blinded subjects with meals of varying caloric content, the participants who are habitually active do a better job of adjusting their subsequent energy intake.

How do we reconcile these seemingly contradictory observations?

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 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 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!


Is Modern Work Draining Our Attention Spans? Podcast with Dr. Gloria Mark

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 instant access to one another, even when we are very far away from one another.

In turn, other people – as well as our devices – have the ability to reach out to us. And they can seize our attention, literally 24 hours per day, seven days per week.

But how does this intimate and constant relationship with technology affect our brains?

Some researchers have begun to examine the impact of digital tools on how we think and perform. Perhaps unsurprisingly, the results are not entirely rosy.

In this episode of humanOS Radio, Dan speaks with Gloria Mark, who is a professor in the department of informatics at UC Irvine. 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.

Much of this research has investigated what we commonly refer to as “multi-tasking.” You already know this: when you are rapidly switching between two different activities, typically your performance on both tasks markedly declines.

This area of research has also examined the impact of interrupted work, which often manifests itself in the form of digital notifications, like from email, text, or phone apps. For most of us, this is a normal aspect of our daily life. But you might not appreciate the full impact that this has on you.

For instance, in one study in which she and her colleagues continuously tracked employees at a tech company, they found that office workers who are interrupted take about 25 minutes to return to whatever task they were working on. And impaired productivity may not be the only price we pay. Gloria’s research has revealed that these kinds of disruptions also ramp up physiological stress levels, as well as increase subjective feelings of stress and frustration.

So what can we do about this? Fortunately, Gloria has come up with some plausible ideas for how individuals and organizations can reduce the cognitive costs associated with digital distractions. To learn more, check out the interview below!


Sunlight for Weight Control? Podcast with Scott Byrne

When we talk about sunlight in the context of health, the picture is usually quite negative. This is because of the well-understood link between ultraviolet light and skin cancer. Ultraviolet radiation penetrates deeply into the skin and generates DNA-damaging molecules. Over time, this can result in mutations and ultimately in cancer.

There is no doubt that excessive exposure to sunlight can be harmful. But research increasingly suggests that too little sun may be just as detrimental. A host of studies have shown, for instance, that living further from the equator is associated with increased risk of multiple sclerosis, and perhaps other autoimmune conditions. Lack of sunlight has also been linked to greater risk of cardiovascular disease and type 2 diabetes. Why is this? Some very clever researchers are starting to investigate this, including our guest for today.

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. At the same time, other researchers also pointed to interesting links between sunlight exposure and cardiometabolic disease.

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, especially if you are someone who routinely shrinks away from the sun (like me). To learn what they found, and more about the far-reaching effects of sun exposure on human health, check out this interview!


The Role of Advanced Glycation End Products in Aging and Disease. Podcast with Pankaj Kapahi

Have you ever wondered what makes cinnamon rolls so irresistible? I don’t know about you, but whenever I walk past a Cinnabon, I am bombarded by an unmistakable and mouth-watering aroma.

But what exactly makes them smell and taste so wonderful? The ingredients alone don’t explain it. Like, if I put white flour, hydrogenated oil, artificial flavors, cinnamon, and sugar (a lot of sugar) in a bowl, it wouldn’t produce that characteristic Cinnabon fragrance, nor would it taste particularly good.

You can see where I’m going with this. Obviously, the cooking process is the mediating factor here. More specifically, I am referring to the Maillard reaction. When amino acids and reducing sugars are exposed to high heat, hundreds of flavor compounds are generated. Food generally becomes browner, and it tastes and smells extra enticing. And this feature is obviously not exclusive to cinnamon rolls. The scent and flavor of roasted coffee, toasted marshmallows, fried bacon, grilled burgers, freshly baked bread, are all results of this chemical reaction.

Humans almost universally gravitate to foods that have been exposed to this process. However, our affinity for these compounds is a bit of a paradox, because of the negative long term effects that they seem to have on our health.

On this episode of humanOS Radio, we welcome 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 also 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.

As I mentioned above, 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!


Interpersonal Neurobiology and the Power of Mindsight. Podcast with Dan Siegel

What is the mind? This is a question that has inspired intense debate for centuries.

We tend to think of the mind as being our thoughts, feelings, and other cognitive faculties. But some would argue that this is a relatively narrow view, in light of our history as social organisms. Our brain evolved, at least in part, as a processing system for social information.

The mind does not just encompass what is within us – it is also between us. And that brings me to our guest for this episode.

On this episode of humanOS Radio, Dan talks with Dan Siegel. Dr. Siegel is a clinical professor of psychiatry at the UCLA School of Medicine. 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. Mindsight is a theoretical construct that is closely 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 recognize our 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!


Sleep and DNA Repair. Podcast with Lior Appelbaum.

Sleep is a paradox – or at least it seems that way when examined from an evolutionary standpoint.

When we’re asleep, we have diminished awareness of our surroundings, leaving us vulnerable to predators and other threats in the environment. Lying down with your eyes closed for eight hours also seems like a frustratingly unproductive behavior.

Despite the obvious disadvantages, we spend about a third of our life in slumber. And not just us – some form of sleep seems to be just about universal in the animal kingdom. And as everyone knows all too well, disturbances to sleep can have a serious negative impact on our physical and mental health.

The universality of sleep, in the face of its costs, suggests that sleep is extremely important. But why precisely do we need it so much?

It has been suggested that sleep may play a role in DNA repair. For example, a study from earlier this year found that on-call doctors who were required to work overnight showed a decrease in DNA repair gene expression, compared to doctors who did not work overnight. Just a single night of sleep deprivation resulted in greater DNA damage, in the form of double-stranded DNA breaks.

In this episode of humanOS Radio, Dan speaks with Lior Appelbaum. Dr. Appelbaum is an associate professor of Life Sciences at Bar-Ilan University in Israel.

Lior and his team performed a series of elegant experiments using zebrafish to elucidate how sleep facilitates DNA repair. They genetically engineered zebrafish to express colorful chemical tags on chromosomes within their neurons, making it easier to identify and monitor them. Then, using a high-resolution microscope, they followed the activity of these chromosomes while the zebrafish were awake and asleep. What they found could reveal the fundamental purpose of sleep, and might explain why sleep is so crucial for cognitive performance and brain health. Check out the interview to learn more!


Does Metformin Block the Health Benefits of Exercise? Podcast with Ben Miller

Physical exercise is one of the best anti-aging interventions at our disposal. Research has shown, for instance, that cardiorespiratory fitness is one of the strongest predictive factors for survival into old age. In one study, men with the lowest exercise capacity were 4.5 times as likely to die within the follow-up time period, compared to those with the highest exercise capacity. And in men aged 75, exercise capacity was the most powerful predictor of survival to age 90, exceeding that of conventional risk factors like smoking, high blood pressure, total cholesterol, and obesity.

So if you want to live a long and healthy life – and who doesn’t? – exercise is a key tool to make that happen. But in order to further push the limits of lifespan and healthspan, it is thought that pharmaceutical drugs to target the aging process may be needed.

One well-elucidated candidate is the anti-hyperglycemic drug metformin. While it has classically been used to help control blood sugar in people diagnosed with diabetes, it has recently emerged as a possible anti-aging drug. This is largely because systematic reviews of the literature have found that patients with diabetes who take metformin have reduced risk of cardiovascular disease, cancer, and all-cause mortality – not just compared to other people with diabetes, but even in comparison to non-diabetics! It appears to extend lifespan and augment health independent of its effect on diabetes.

But some have wondered if metformin might come with some serious downsides, particularly with respect to the aforementioned health-promoting effects of exercise. Our guest today endeavored to answer that question with his latest study.

On this episode of humanOS Radio, we welcome 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. Check out the interview to learn more!


Optimizing Your Gut Microbiome with Personalized Probiotics. Podcast with Richard Lin

We like to think of ourselves as wholly distinct organisms – separate from the environment around us, and independent of other organisms.

But zoom in closer, and the truth is far more complicated.

We have vital symbiotic relationships with an unfathomable array and quantity of microorganisms on us, and within us. Perhaps the best known example of this phenomenon is the gut microbiome. The number of microorganisms inhabiting the gut has been estimated to be around 10 times more bacterial cells than human cells. Wow!

Given their staggering numerical superiority, it really shouldn’t be terribly surprising to learn that the amount and types of bugs you carry in your gut can make a big difference in how you feel and perform. But it is only in the last fifteen years or so that technology has enabled us to fully appreciate the far-reaching influence of the gut microbiome in human health. And as we’ve learned about ways to modulate the gut microbiota, this has become an area of tantalizing potential.

Consequently, many tools have emerged that purport to enhance the composition and functional properties of gut microbes. Commercial probiotics – live cultures meant to colonize the gut with “good” bugs” – have skyrocketed in popularity. At the same time, companies have also emerged that offer personalized analysis of the microbial content of fecal samples.

However, the human microbiome remains an enigma in many ways. For instance, by what criteria can we identify what is a “healthy” versus an “unhealthy” gut microbiome? And even if we are able to make such determinations, are we able to make lasting improvements?

That brings me to our guest.

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 the future of microbiome testing and probiotics, please check out the interview!


Increasing Mitochondrial Autophagy for Better Aging. Podcast with Davide D’Amico

You probably associate getting older with a loss of energy. And 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.

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

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