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!

#068 - Carbohydrate Availability, Energy Balance, and Exercise - Dr. Javier Gonzalez.

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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.

092 - humanOS Radio - Vijay Yadav - Taurine On Health And Lifespan (2023.06.20)

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!

091 - EyeAge Biological Age Clock with Professor Pankaj Kapahi

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.

#090 - The Effects of Glylo on Weight Loss, Blood Sugar, and Longevity - Professor Pankaj Kapahi

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!

#089 - The Role of Acid-Base Balance in Health - Dr. Lynda Frassetto

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!

#068 - Carbohydrate Availability, Energy Balance, and Exercise - Dr. Javier Gonzalez.

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