In Depth: Understanding Circadian Rhythms

In Depth: Understanding Circadian Rhythms

Breakthrough research into the biology of time is uncovering how restoring natural rhythms could help stave off disease.

Satchidananda (Satchin) Panda, PhD, is a professor at the Salk Institute in California, where his research focuses on the circadian regulation of behavior, physiology and metabolism. Two decades ago, Panda contributed to the discovery that a blue-light sensitive protein called melanopsin is critical for regulating our body’s circadian clock. More recently, his lab pioneered research into how time-restricted eating—confining caloric consumption to an 8- to 12-hour period—could help prevent a host of health problems. 

What motivated you to study the circadian clock and its role in health? What are you trying to figure out?

When I was finishing my undergrad and master’s studies in India, I realized that although we know a lot about biology, it is mostly linked to what and how much. For example, we know what kinds of genes and proteins affect metabolism or behavior. However, the when aspect was very little explored at that time. I became interested in what I call the biology of time: how biological systems keep track of time, how they respond in a time-of-day dependent manner, and whether the disruption of timing contributes to disease.

The word “circadian” means 24-hour rhythms, and these rhythms are tied to the rotation of our planet around its axis. Humans and almost every other organism on this planet evolved based on this 24-hour day and night cycle. However, over the past 150 years or so we have created a man-made environment that ignores this 24-hour rhythm and sometimes actually requires disruption of the circadian rhythm. For example, nearly 20% of working adults in Western countries work as shift workers, and most high school and college students stay awake late into the night studying for exams. This widespread disruption in our internal clocks is, in my view contributing to an increased risk for many chronic diseases, such as diabetes and depression and even dementia and cancer. My research could help reveal how the principles of circadian rhythms could be used to rebuild this anthropogenic world in a way that might prevent, cure and reverse disease.

Tell us more about the approaches you’re using to study circadian rhythms and disease.

I use different model systems, including fruit flies and mice, and we also do human studies. We ask very simple questions such as: If a gene is disrupted, does it lead to circadian rhythm disruption? Does disrupting the light-dark cycle lead to circadian rhythm disruption? Do disruptions in the feeding-fasting cycle cause circadian rhythm disruption? We also study very simple outcomes such as growth rate and sleep, as well as changes in the amount of fat and muscle and variations in heart rate.

Team science is extremely important for circadian rhythm research because we need specialists who can carry out various kinds of biochemical or physiological assessments. Collection and analysis of large amounts of data requires  the expertise of computer scientists, data scientists and statisticians. I also collaborate closely with physicians and physician-scientists to study the circadian rhythm in people. 

What are some of the most important findings that have resulted from your research? 

Almost 22 years ago, our team, together with two other labs, co-discovered that a protein present in just a few cells in our eyes senses blue light around us and then sends that information to the master clock in the brain to tell us whether it’s morning or night. This finding transformed how we light hospitals and the light cycle used in neonatal ICUs. It has also allowed us to understand how lighting can be optimized to improve performance among schoolchildren or to reduce the severity of dementia among older adults.

Another important finding from our lab is that most of our genes turn on and off in different organs at specific times during the 24-hour day. The fact that every organ has its own clock means that the circadian aspect of almost every disease can now be traced back to mechanisms in the respective organ. This has important implications for understanding diseases and for optimal timing of medication. 

What has your research revealed about time-restricted eating?

In 2012, we published a very simple but profound study. We divided mice into two different groups. One group was allowed to eat whatever and whenever they wanted from a fatty, sugary diet. The second group was given the same number of calories and quality of diet as the first group but all within an eight-to-nine-hour period each day. After 16 to 18 weeks, the first group became obese, diabetic and had signs of heart and liver disease—almost every metabolic disease that can happen to these mice. Surprisingly, the second group of mice, even after eating the same number of calories from the same fatty, sugary diet, were completely protected from all these diseases.

There are now more than 150 clinical trials related to time-restricted eating being performed around the world. We hope that these studies will show who can benefit from this approach and whether it can be further amplified by combining it with drugs and other interventions.

What’s next for your research?

There are three foundations of health: nutrition, sleep and physical activity. We know that sleep disruption leads to various problems, but we don’t know why or how. We’re working to systematically understand how sleep disruption affects our immune system and metabolism, for example. We are also working to better understand physical activity. There are so many diseases that can be prevented or cured with exercise, but at the same time we don’t know how exercise affects physiology. This work will provide new insights into how lifestyle changes can be used to improve health.

Interview conducted by science writer Nancy D. Lamontagne.

This article was originally published in the May 2024 issue of The Physiologist Magazine. Copyright © 2024 by the American Physiological Society. Send questions or comments to tphysmag@physiology.org.