Introduction:
Welcome to the Salk Institute’s 治愈的起点 podcast. Where scientists talk about breakthrough discoveries with your hosts, Allie Akmal and Brittany Fair.

Allie Akmal：
I’m here today with Professor Satchin Panda, who explores the genes, molecules and cells that keep the whole body on the same biological clock, also known as a circadian clock. “Circadian” comes from the Latin word, circa meaning approximately and dies meaning day. We’ll be talking about various aspects of these fascinating 24-hour rhythms, including their many implications for human health. Professor Panda, welcome to 治愈的起点.

Satchin Panda:
Thank you, Allie. I’m glad to be here.

Allie Akmal：
We’re delighted to have you. Circadian rhythms are obviously fundamental to life on earth since organisms evolved on a spinning planet that gives us a 24-hour day-night cycle. Why is it important for cells to keep track of time?

Satchin Panda:
Well, on this planet ever since life started, there has been only one predictable change that happens every single day. The sun goes up and it goes down. And with that, it’s not only light, it’s the availability of food, the humidity in the air, temperature, almost everything that’s surrounding an organism changes in a predictable fashion. So that’s why from single cell to the whole animal or plant, [we] can predict these changes and adjust the physiology and metabolism so that they can thrive.

Allie Akmal：
So they can thrive, I see. So what is the connection of circadian rhythms to health?

Satchin Panda:
Over the last 20 to 25 years, there are many lines of research that have come together to emphasize what is the importance of circadian rhythm. In laboratory studies, we can take mice, rats and fruit flies and put them under continuous light—or endless summer [laughter] or endless winter without changing their genes, without changing anything. And we do see that very quickly within a few weeks or a few months, these animals will develop diabetes or high blood sugar, they can have blood diseases, they might gain weight. So all of these chronic diseases happen.

Allie Akmal：
You’re saying that disrupting circadian rhythms in lab animals causes them to develop health problems. But how do we know being out of synch with our circadian clock is a problem for humans?

Satchin Panda:
Then the second line of evidence is, we do have a lot of shift workers and when they go back and forth between a day and night shift, their circadian rhythm is disrupted.

What we find is shift workers are at very high risk for all of these diseases: high blood pressure, diabetes, gut disease, cancer, being overweight and heart attack.

Then the third line of evidence is, if we bring people—healthy volunteers—and just give them circadian disruptions just like the shift workers too, within a week or two, we can see early signs of diabetes, early signs of blood pressure going out of control, or they will start complaining about acid reflux, which is an early sign of gut disease.

So all of this points to this common idea that, well, when you disrupt the circadian rhythm, then you can get many of these chronic diseases. Right now in the US, almost half of our adult population have high blood pressure, a hundred million people with diabetes, and 140 million people are overweight. Almost every year, half a million people are dying of heart disease. And there are 17 million people who have survived cancer. So if we look at the disease burden of the nation, then it comes to mind, are there some aspects of circadian disruption that’s driving some of the disease? Conversely, if we optimize circadian rhythm, can we move the needle? Can we prevent maybe 10 million people from getting diabetes? Can we take care of maybe 10 to 15 million people who will reverse their hypertension? Early experiments are showing that yes, we can. I think it’s time to say there is a circadian theory of health—the circadian theory of longevity, because by having healthy circadian rhythm, we can prevent many of the chronic diseases.

Allie Akmal：
What’s so interesting to me about this circadian theory of health is that it doesn’t necessarily involve any fancy equipment, gadgetry or medications. There are things that people can do at home in their own lives to improve their synchronization with their circadian clocks and those involve when you eat, when you sleep and when and how much exercise you get. So can you talk a little bit about that?

Satchin Panda:
Yes. Everybody can optimize their life a little bit and some people can optimize a lot. Numerous epidemiological studies in multiple countries involving millions of people have shown that people who sleep between six and a half to seven and a half hours have the least disease burden, and they live longer. So let’s begin with that.

Voiceover:
And besides getting enough sleep, Panda says other things we can tweak to be more in synch with our daily circadian rhythms are exposure to sunlight, exercise and eating within an 8-to-10-hour window of time.

Let’s start with sunlight, which is our main source of blue light. Panda is one of the discoverers of a protein in the eye that senses blue light. It’s called melanopsin and it tells the master clock in our brain that it’s daytime. But that’s not all.

Satchin Panda:
We also found that the same melanopsin light sensors sense bright light and improve our mood. So that means bright light can reduce depression. And in fact, we know that in winter time, when people don’t go out and get little light indoors, they get “winter blue.” And now new research is showing that people who are depressed, if they get 45 minutes to an hour of bright light—you don’t have to sit outside and look at the sun—even if you’re under a tree or even if it’s an overcast day or cloudy day in winter time, there is enough light for 45 minutes to an hour that can reduce depression. And in this country, every year, 6 to 7 million people go see their doctors for depression. If light is the best antidepressant and is plentiful and free, you just have to step outside for half an hour.

Allie Akmal：
And when you step outside…?

Satchin Panda:
And when you’re outside, don’t just stand there. If you move around 30 minutes every day, that adds up to 150-200 minutes of physical exercise.

Voiceover:
That’s around two and a half to three and a half hours per week. I probably spend that much time streaming shows and munching popcorn every night! Which brings us to his next point:

Satchin Panda:
When to switch off the light. And what we’re finding is maybe two to three hours before going to bed, one should stop eating and one should dim down the light so that we can build up our natural melatonin hormone that help us sleep.

Voiceover:
So the other side of the coin of getting exposure to bright light is that we need to limit it at night, because our screens—smartphones, computers and TVs—also emit blue light, which can keep us from getting sleepy. And what was that about stopping eating?

Satchin Panda:
And what we’re finding is maybe two to three hours before going to bed, one should stop eating.

Voiceover:
Panda says that most Americans, on average, eat 15 hours out of every 24 [hours] every day. Maybe it’s orange juice or coffee with cream at 7 a.m. and a bowl of ice cream before bed at 10 p.m. So the body doesn’t get enough of a continuous break from digestion to do other important cellular housekeeping. His research suggests that only consuming calories within an 8-to-10-hour window—7 a.m. to 5 p.m. or 10 a.m. to 8 p.m., for example, is healthful. The exact window is whatever works best for the individual. And if it’s easier to start with a 12-hour window and shorten it over time, that’s fine too.

Satchin Panda:
There are studies after studies coming out showing that this pattern of eating, which is time-restricted eating or intermittent fasting, if it is practiced, then people do see a drop in blood pressure to a healthy range and also reduction in blood glucose to a healthy range. So this very basic idea of nurturing circadian rhythm by timing sleep, food, going outside and getting some light, is beginning to show health benefits. And the nice thing is, as you mentioned Allie, since it doesn’t involve any additional costs, we also think that this is the best way to address health disparity, not only in this country [but] globally, because we know that there’s a huge health disparity in this country. But I think the circadian wisdom—the circadian theory of health will reduce that health disparity.

Allie Akmal：
Where do shift workers fit into this picture?

Satchin Panda:
Twenty percent of our workforce does shift work and then another 10 percent to 20 percent are gig economy where they’re not classified as shift workers, but they work in random hours. And then if you think of the family members, they’re also exposed to circadian disruption—so I call it the second-hand shift workers. So nearly half of our adult population undergoes some kind of circadian disruption, or they witness somebody who is going through that circadian disruption. So this is where not only being aware about circadian rhythm will help, but there should be opportunities [to help]. So we have to change when, for example, kids should go to school. We know that teenagers have a little bit of a different circadian rhythm. Their clock is slightly delayed so they tend to wake up later, and then circadian health will involve delaying the school start time. And that’s what we and others have been doing. For example, the University of Washington did a very simple study and what they found was by delaying school start time, the kids could sleep 35 minutes extra. The tardiness at school went down and their grades improved.

Allie Akmal：
Wow. Where do you think the field of circadian biology is headed?

Satchin Panda:
Understanding how the disease mechanism intersects with circadian rhythm is very important. I think what we’ll begin to see is almost every aspect of disease or physiology has some circadian component. And taking that into account and developing a strategy where we can combine pharmacology or drugs with optimum circadian function, will be the way forward for treating almost every single disease.

Allie Akmal：
Where did your interest in this field come from?

Satchin Panda:
You know, in my book, The Circadian Code, I have described how the initial interest started when I was a child. One of my grandparents—grandfather who worked almost like a shift worker in the Indian railway, oftentimes he worked at nighttime. And on the other hand, my other grandfather lived in a farm and was in complete sync with his circadian rhythm and day-night cycle. That gave me a very stark contrast between two different lifestyles. My maternal grandfather got dementia and passed away in his early seventies. Whereas the other grandfather who lived in a village, he lived to his early nineties and that kind of sparked my interest. And then I went to graduate school—I wanted to be a geneticist.

Then I began to see that, well, there is a huge amount of biology of time that goes on around us and we haven’t paid attention. Almost every disease that we see has a timing component. For example, if you take simple diabetes, the first thing that happens is after we eat, blood-sugar level might rise for a little while, but it should go back in 90 minutes or so. And if it takes a couple of hours, three hours or four hours, then we get closer to diabetes. So it’s a disease of timing.

So I realized that people are trying to know in physiology and biology, how gene A interacts with gene B, but what is also equally important is when does that interaction happen? How long should they interact for, when should it stop? We are just scratching the surface of timing in biomedical research. And that’s how I got interested.

Allie Akmal：
And now you’re at Salk where collaboration is very, very important and working across disciplines is encouraged and your work has relevance to a lot of different areas. In fact, we have these various research initiatives: optimizing aging, conquering cancer. And so your work really feeds into all of these research efforts that are going on at Salk.

Satchin Panda:
Yes. So that’s why I feel like I’m a kid in a candy place [laugh] because almost everybody’s work excites me. Salk is an exciting place because we have all this multidisciplinary approach to most of the basic science questions, and we do see that circadian rhythm has its impact on almost every field. For example, for cancer prevention, a few years ago, when we first tried a circadian drug that targets a circadian clock component to see whether it can treat cancer—it is only feasible because at Salk Institute we can just walk 10 feet or 10 meters and find an expert in cancer [laugh]. And that’s how we made the discovery that yes, circadian drugs can actually treat cancer.

You know, in the US we have only two to three centenarians per ten thousand people, whereas in Japan, it’s approaching five.

Allie Akmal：
好的.

Satchin Panda:
So now, can we have a goal that we should have 10 centenarians per ten thousand people? Then that will drive our research and our vision about how we take basic science discovery to translation, to patient care and improve health. And so that everybody can meet that universal human rights to be physical, emotional and intellectually healthy from childhood to 100 years.

Allie Akmal：
Well, that’s a very inspiring goal and there’s an app that your lab has developed that might help people on an individual basis. Would you like to talk a little bit about that?

Satchin Panda:
Yes, so we developed this app a few years ago called MyCircadianClock. Anyone, anywhere in the world can go to the website with simple informed consent and download it and use the app. To create the culture, we have to give knowledge and opportunity to practice. So that’s why we have this app. It has been used by tens of thousands of people.

Five years ago, when we started the app, we thought we had an uphill battle to let people understand what is circadian. And it’s gratifying to see five years later that there are at least five different apps and have at least five to 10 million people around the world who are now following their own circadian rhythm.

Allie Akmal：
Wow. That’s amazing.

Satchin Panda:
And the app also helped us to translate basic science discovery to humans, not only directly to consumers, but through the app, we are collaborating with at least a dozen different labs who are using the platform to optimize circadian rhythms among their respective patient populations, with a goal to reduce weight, to reduce fatigue and improve recovery from cancer, to manage metabolic syndrome, to manage diabetes and manage fatty liver disease. All over the world, there are nearly 50 clinical trials going on around time-restricted eating or intermittent fasting.

So this is gratifying to see that bringing simple technology in the form of an app and combining that with patient care and creating a resource platform, actually enabled us to go from basic discovery to do potentially clinical practice within 10 years. I mean, there are very few examples where basic discoveries have gone to practice within that timeframe. So that’s good.

We can actually make some measurable change in patient care. We can reduce the burden of disease. And I must say, it would not have been feasible in any other place other than Salk, because only here we have a strong scientific community, and we have a passionate, dedicated staff who are very supportive of scientists. And we also have philanthropists and board of trustees who recognize potential innovation. So that’s why we have various mechanisms of innovation grants and other stuff. And Allie if you really—if we just take a pause and think about all the big discoveries made in Salk, most of them can be traced back to some of these grants or some philanthropic support, those early investments actually make us take a big bet and try bigger ideas. I’m very thankful to be here.

Allie Akmal：
That’s wonderful. Well, we’ve talked a lot about your work. What kinds of things do you like to do when you’re not at work?

Satchin Panda:
[laugh]. I know that’s a tough question nowadays, because of the COVID. Yes, when I’m not at work, I’m at home. We are on the top of a canyon, and there is a canyon reserve. So that means there are quite a few wild animals. We have a bird feeder and—people always make fun—but actually I have the bird feeder on a timer [laugh]. The birds are trained. They can anticipate when the timer or the feeder opens. So they come 15 minutes to half an hour before the feeder opens, they wait and they eat. And also, it’s interesting to see that different species come at different times of the day.

Allie Akmal：
Oh, that is interesting.

Satchin Panda:
Yes, the doves come early, then the sparrows come and then the California [scrub] jay comes at around nine or nine thirty in the morning. And then at night, there is a screeching owl that also comes in once a month, [it] kind of disturbs my sleep [laugh], then the coyotes and the raccoons come. So it’s kind of interesting to go back to that ancestral life, you can say, and experience that. So that’s what is happening outside work these days. Otherwise, during pre-COVID, I used to travel a lot. The best time to enjoy a city is actually very early in the morning. Since you’re jet lagged, it’s very natural to wake up around four o’clock in the morning, then go for an early run. And everything is quiet, and the city is kind of waking up—not too many tourists and I used to have my camera. So I enjoyed that very early morning—photography in the city, when there’s no one around.

Allie Akmal：
So it sounds like you’re a keen observer of both nature and human spaces.

Satchin Panda:
Yes. You can put it that way, Allie [laugh]. Sometimes when I get too passionate about circadian rhythm, people always think that, well, you are talking as if this is going to solve all the problems. The circadian theory of health can give us a framework to move forward. And it’s not that everybody can practice circadian optimization, can practice time-restricted eating, or can be in bed for eight hours every night, but the idea that at least 10 percent of people can benefit—and that 10 percent can be 10 million people in the US alone, that’s pretty impressive. And that’s what keeps me going.

Allie Akmal：
Thank you so much for spending this time with us.

Satchin Panda:
Thank you, Allie, and have a wonderful day.

Ending:
Join us next time for more cutting-edge Salk science. At Salk, world-renowned scientists work together to explore big, bold ideas from cancer to Alzheimer’s, aging to climate change. 治愈的起点 is a production of the Salk Institute’s Office of Communications. To learn more about the research discussed today, visit salk.edu/podcasts.