SATCHIDANANDA PANDA – Professor, Regulatory Biology Laboratory: So pathogens like this used to cause infectious diseases that killed humans for centuries. Until sanitation, vaccination and antibiotics took care of pathogens and gave us long, healthy lives.
But now, we spend nearly half of our life fighting with these kinds of chronic diseases, and for which there is no cure in sight. So today, I’ll share with you some really revolutionary ideas of how to prevent, manage and cure these diseases. And the idea is based on the concepts of circadian rhythm, our near-24-hour rhythms. To adapt to the 24-hour light-dark cycle, or day-night cycle, on our planet, almost every plant and animal has circadian rhythms that are controlled by what we call circadian clocks. These are actually encoded in our DNA.
And this is so fundamental to life forms on our planet that if we move any animal or human from this planet to another planet that has identical conditions as the planet Earth but has a day-night cycle other than 24 hours, then we cannot easily survive. In recognition of this fundamental property of circadian clocks and health, this year’s Nobel Prize was actually awarded to three scientific leaders in this field. And I’m really honored that all three of them have directly inspired and influenced my research.
So how do we know that these clocks are in-built? For example, if you lock me inside an apartment with no clue about outside time, then my circadian clock will make me go to sleep around 10:00 at night. I’ll go into deep sleep around 2:00, and anticipating waking up, my body will warm up around 4:00 in the morning.
As soon as I wake up and open my eyes, my sleep hormone melatonin will plummet, and my stress hormone cortisol level will rise. My peak performance time for brain will be around noon. And my peak athletic performance will happen around late afternoon. As evening rolls in, the circadian clock will crank up melatonin to make me go to sleep again, and my body will cool down to support my sleep. So this will continue every 24 hours, even if I’m locked inside an apartment.
And these rhythms happen because almost every single gene in our genome turns on and off at different times of the day. Every single hormone and brain chemical also rises and falls at different times of the day. So to have these rhythms is actually to have health. And when these rhythms break down, when we stay awake late into the night finishing an assignment or taking care of a loved one, then we feel horrible the next day. And if we continue abusing our clock for weeks or months, then all these chronic diseases can happen.
So it’s very important, then, to know how are these clocks organized so that we can nurture them much better. So as you can imagine, just like in our brain we have a clock that makes us go to sleep and wake up every day, the same brain clock sends chemical signals to the rest of the body.
But what is really surprising is that almost every organ in our body, and even every single cell in our body has its own clock. What does that mean? It means that just like your brain clock makes us more efficient at solving complex problems in the middle of the day, and also the brain needs to sleep at night, every organ has its own peak performance time at certain times of the day. And every organ needs to sleep, or rest and rejuvenate, at another time.
So all these clocks work together to give us daily rhythms in sleep, metabolism, mood and even gut microbiome. But how are these clocks connected to the outside world? In fact, every morning as we wake up and open our eyes, bright light goes through our eyes and resets or synchronizes this clock, so that when daylight savings time changes, or when we move from one time zone to another time zone, light synchronizes all of our clocks to the new season or the new time zone. But the property of light that resets our clock is very different.
Almost 15 years ago, we discovered a new blue-light-sensing protein called melanopsin. It’s present only in 5,000 squiggly neurons in our eye. And these light-sensing neurons are literally hard wired to our brain clock, to the master circadian clock. But they have a very interesting property. They’re less sensitive to light, and especially to orange colored light. So that means, in the evening, as we move around and find our way under candle light or dim orange light, the melanopsin is not activated. It sends a signal to the brain as if it’s dark outside so that the brain clock makes a lot of melatonin and we get a good night’s sleep.
And in the daytime as we wake up, go outside for at least an hour or so. The daylight is very rich in blue light. It fully activates melanopsin. That synchronizes the brain clock nicely with the day. It reduces sleepiness and depression, and increases alertness.
But the problem is, we spend more than 90 percent of our time indoors. And at nighttime, bright screens and bright light activates melanopsin; it sends a confusing signal to the brain, and the brain thinks it’s not night yet, so it produces less melatonin, and we sleep poorly.
The next day when we wake up, as we spend most of our time indoors, this indoor light is not rich in blue light, so it again sends another confusing signal to the brain, and the brain thinks it’s not day yet. So all the chemicals that should boost our mood are actually not produced enough. So we kind of go back and forth between insomnia and fogginess, and if it continues for weeks or months, then a lot of diseases can happen.
And what is interesting is, this is particularly important for children because their brain is still developing. And when children go through early childhood circadian disruption, they are more prone to diseases like ADHD and autism. So this new simple idea, that we need more bright blue light during the daytime and less light, or darkness, at nighttime, is starting a new lighting revolution. And you are just getting a glimpse of this new light revolution when your smart screen and computer screen dim down and turn orange at nighttime. But there is more to it.
Just think about it: Circadian lighting at daycare and schools will promote healthy brain development and promote learning. Circadian lighting at home, factories, offices, will promote alertness and improve productivity. Circadian lighting at hospitals or retirement homes will promote health and accelerate healing. And in fact, right now, there is new circadian lighting in our International Space Station to promote productivity of our astronauts and make them have better nights’ sleep. So light is not the only factor that affects our clock.
In fact, just like light in the middle of the night disturbs the brain clock and breaks the chemical balance in our brain, food at the wrong time can disturb the peripheral clock and break the metabolic balance in our body, and that will push us towards disease.
Now, let’s figure out how. So in the morning, our stomach is actually ready with the right amount of hormones and digestive enzymes, and even good gut microbiome to digest food. So after we eat our first breakfast, a body absorbs enough carbohydrates and uses it to fuel our body. At the same time, it saves a little bit of nutrient as fat.
As we continue at lunch and dinner, the same process continues. And after the last dinner, last bite, a body slowly goes low on carb. At the same time, the circadian clock cranks up morning fat. And after a few hours, the clock turns into a reset and repair rejuvenation mode. That means that it turns on enzymes that will break down cholesterol and toxins.
It also turns on mechanisms to repair the DNA that we have damaged during the daytime. And a lot of cells that are damaged on our stomach lining or our skin lining are also replaced with healthy new cells so that allergy-causing chemicals or bacteria cannot get into our body. So after 12 to 16 hours of fasting, when we eat our next breakfast, the cycle of nurture, rejuvenation continues. But imagine if we delay that last bite late into the night. So in this case, this daily rhythm in metabolism becomes shallow.
There is not enough time to burn fat, and there is not enough time to break down the toxins, cholesterol, etc. So, you can imagine that somebody who eats within ten hours might have a much better circadian rhythm, whereas somebody who eats within 15 hours may not. To test this idea, we went back to the old lab and brought two identical groups of mice born to the same parents, raised in the same room, same age. And one group of mice got the standard Western diet to eat whenever they wanted. And then the second group was trained to eat the same number of calories from the same food, but they had to eat everything within eight to 12 hours at nighttime when they’re supposed to eat.
And we measured the food and weighed the mice carefully every week for almost 18 weeks. At the end of 18 weeks, the first group of mice, who ate randomly, were obese, where at the same time, they had a host of different diseases – they were really morbidly sick – where the second group that ate within eight to 12 hours were completely healthy. But what is more surprising is this: If we take those morbidly sick mice and give them the same diet, same number of calories, and they have to eat only within eight to ten hours, they become healthy. This was a really earth-shattering, eureka moment for us, because for the first time in the history of nutrition science, we found that when we eat is as important as what or how much we eat.
Well then, how do we translate that to humans? The first thing we wanted to know is, when do people eat? To do that, we started a new study – and people usually sign up for the study at mycircadianclock.org – and then, since people love to take pictures, we asked them to take pictures of every single thing that they eat or drink, and we’d do the rest. So when the pictures come to our server, we add them on a timeline so that it’s easy for us to figure out when they eat. And they continue taking pictures for almost two to three weeks. So that we can take a nice snapshot of their food life during the weekdays and weekends. And you can see, for this particular person, he or she eats very randomly throughout the day.
And if you look at the weekday and weekend pattern, those are also very random. And if you combine the weekday and weekend, there is another interesting thing that comes up. It appears as if the person is on the East coast during the weekday and comes to the West coast on the weekend, which is also very bad for our circadian clock. Now, if we combine all of this data and plot it as if we are looking at a clock, then you can see that this person was eating almost around the clock. He’s not an outlier, actually.
If we look at the first 150 people who had signed up, nearly 50 percent of adults who actually have regular 8 to 5 jobs, eat for 15 hours or longer. So that means if they have their first bite at 7:00 in the morning, the last bite or last sip of wine happens at 9:00 or later. What is interesting is, if we feed mice even a healthy diet, and they eat for 15 hours or longer, then slowly they become overweight and they get all these diseases. So that’s why we wanted to ask a very simple question. We brought back people who were eating for 15 hours and were a little overweight, and asked them to eat whatever they want within ten hours of their own choosing, and we wanted to see what happens to them.
So within three to four months, these people actually boosted up their circadian rhythm and they lost the excessive body weight that they had. And over the last one year, we’ve had thousands of people from all over the world who are signing up either through our study or doing this by themselves. They try to eat all of their food somewhere between 8, 10 or 11 hours. And when they do that, after a few weeks, they’re truly amazed by the untapped potential of the healing power of circadian rhythm. Almost all of them lose a little bit of weight, but as they continue, they actually feel much better, more energetic throughout the day.
They sleep much better at night, and their mood is much better; they feel very sharp. And slowly, over months, they suffer less from different diseases of the gut, heart, immune system, diabetes and even some of the mental diseases. So we’re truly excited about this study, but at the same time, we learned another very important insight, and let me share that with you. That is, circadian clock tunes the potency of almost every drug that we take for almost every disease. So that means, at certain times of the day, the drug is more potent and can cure you, but at the wrong time of the day it can have a more severe adverse effect, as if it’s a poison.
So this is really important. And the effect is not even only to drugs, at what time of the day we take our flu shots, at what time we schedule our surgery for liver or heart, does matter. Even cancer patients who are going through chemotherapy or radiation therapy, it really matters whether they schedule the chemo or radiation in the morning or late in the afternoon. So this new knowledge about circadian rhythm is poised to start a new revolution in healthcare and healthy habits. Because the current idea of taking care of your health by counting calories and counting steps is just prehistoric.
And the same software and tools that our tech companies are using to make us watch more arts, sleep less and eat around the clock can be used for something better. We can have devices and sensors that can create a nice circadian lighting environment around us. Sensors can go on us to monitor our own circadian rhythm every day and how it interacts with the real outside world. Devices can prompt us what to eat and when to eat to boost our circadian rhythm. And even there will be smart pills and programmed drug pumps that can deliver the right medicine, at the right dose, at the right time, even in the middle of our sleep, so that we can get cured much faster.
So I truly believe that circadian rhythm has untapped potential to prevent, manage and cure many of the chronic diseases that affect billions of people. Thank you.