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!