Rhonda: Every organ in your body essentially is on a circadian rhythm and including your organs like your liver that are involved in metabolism, you mentioned when we were talking about shift workers, people eating within a certain time window, so time-restricted eating, most people here in the Clubhouse chat probably have heard of time-restricted eating. They're familiar with your work. But maybe we can kind of just briefly explain what it is and why eating within a more narrow window range, your research had shown and others, to be beneficial.

Satchin: So time-restricted feeding, time-restricted eating is something that was discovered in our lab and the term was also coined in our publication. And it has been now used more loosely in popular culture as intermittent fasting. Intermittent fasting, in fact, in scientific literature refers to alternate day fasting, two days of fasting in a week, or even periodic fasting, but people will fast for four or five days in two to three months. But we didn't want to use the word fasting because fasting usually refers to reducing calories for one or more days, whereas the term time-restricted eating generally refers to eating within X number of hours, where the X can be somewhere between 8 to 12 hours in experimental models, preclinical models, and without explicitly reducing calorie. And that's a big caveat between caloric restriction, scientific term intermittent fasting and time-restricted eating. So now, coming back to the science, why we think it is important is if we think of why circadian rhythm is important, one big thing is circadian rhythms actually help our body to repair and rejuvenate itself. For example, we always equate a human body to a car or an engine. And we say how we describe how our body works by connecting it to an engine. But there's a huge difference between a car and our body, and that refers to you can start a car and take it for a spin at any time of the day or night and it will function the same way. It will go from 0 to 60 if you're riding a Tesla, maybe 3.5 seconds, or some other cars, maybe 5 to 6 seconds, it doesn't matter whether it's day or night. But our body doesn't work that way. If I wake you up in the middle of the night and ask you to do a complex piece of math, you might take an hour, whereas in the middle of the day, it might take you only 15 minutes. So the reason being the car doesn't have to self-repair itself. We have to send the car to a body shop or to a repair shop to repair it once every three to four months or tune it up, whereas a body tunes up and repairs itself every single night. And that's why when we misuse our body, we have to send it to the body shop or repair shop, aka a hospital or emergency room. And so that's why you don't want to use your body as a car. So now, coming back to the repair and rejuvenation, now, if you think of sleep as a perfect example, when we sleep for seven hours or eight hours, during that seven to eight hours, our brain is repairing and rejuvenating itself by taking out the toxic materials, by strengthening the synaptic connections or connections between our neurons and resynthesizing some of the neurotransmitters. All this repair and rejuvenation is happening for those seven to eight hours. So now, just like the brain, every single organ in our body also needs to repair and rejuvenate. And for that process to work, you don't want to...so just like the brain is unplugged from all the outside sensory stimulation for this to happen, similarly, all the cells, all the organs in our body has to be unplugged from outside input. And one of the outside input that influences almost all of our organs is food because when we eat, it changes quickly the levels of many hormones. It even changes the nutrient level and all cells in our body have to process or break down, interconvert all the molecules that we get from our food. So that's why we need to stop eating. But then the question is, if our brain needs only seven to eight hours of sleep, why do we need 12 to 16 hours of no food? And the answer is when we eat, it takes at least five hours for our stomach to digest that food. And after five hours, then our intestine might take several hours to absorb nutrients, some of the nutrients, and then send them to our liver and other parts of the body. So that means if you finished your dinner at 6:00 in the evening, then your stomach is still working until 11:00 pm or even later, so it's not actually getting to sleep, or repair, or rejuvenate itself. So that means how many hours you are not eating, you subtract at least five hours from that, that's the number of hours your organs are resting, preparing or sleeping. So that's why if we eat for 8 to 10 hours, then we give our organs some rest for 16 to 14 hours, and that translates to roughly 8 hours of really no digestion, no nutrition interconversion, and that's the time our organs are getting to repair and reset, rejuvenate. So as an experiment, we have done this experiment in mice and fruit flies because we can control eating there. When we give mice ad libitum access to food, they can eat anytime, then they will eat nearly 85% of the food during nighttime when they're awake, 15% to 30% of food during daytime when they typically sleep. And in this lifestyle, the mice will slowly gain weight. They will slowly become diabetic, they will have high plasma fatty acids that will make them prone to heart diseases, and many other bad things will happen. But if we feed the mice the same number of calories from the same diet source, whether it's healthy diet or unhealthy diet, they get to eat all of that food within 8 to 10 hours, then we can protect them from all these diseases. And if the mice are already having a disease and we put them in time-restricted feeding for 8 to 10 hours, we can reverse those diseases. We have done a lot of molecular studies now looking at different organs, looking at the whole genome sometimes, hundreds of metabolites, and we find the molecular mechanisms by which this time-restricted eating is triggering breakdown of toxic materials, detoxification during the fasting time, better uses of fat, protein, and carbohydrate during day and night, and improvement in metabolism and mitochondria function that reduces reactive oxygen species, all of these good things, and improved autophagy. All of these things are happening when mice eat within 8 to 10 hours. And some of these have been now translated to human studies. And some of the pilot studies have come in. The results have come in. They're very promising. And some of the randomized clinical trials are ongoing, and hopefully, we'll get those results from 📍 2021 onwards. 📍