Two leading scientists explain how circadian rhythms work and offer advice on lifestyle changes to improve your health
Highlights:
→ Maintaining consistent and healthy circadian rhythms may help improve overall health and prevent chronic diseases.
→ Think beyond sleep: Circadian rhythms are influenced by eating, exercise, and other factors.
→ Learn the idiosyncrasies of your own rhythms, your “chronotype,” then adapt them to the best practices indicated by scientific research.
Editor’s Note: This story is focused on the science of circadian rhythms, the 24-hour physiological patterns that most organisms, including humans, follow each day. This article is intended to review the current science on the topic and not principally to offer advice, though we do present potential lifestyle modifications. It is not an exhaustive review of the field of research, and we will continue to update it as more science emerges.
As always, any health advice should be discussed with a healthcare practitioner before incorporating it into your routine.
Before You Start: A Quick Glossary
Circadian: Recurring naturally on an approximately 24-hour cycle, even in the absence of light fluctuations; from Latin circa (“about”) and diem (“day”).
Zeitgeber: An environmental cue, such as a change in light or temperature; from German zeit (“time”) and geber (“giver”).
Endogenous: Having an internal cause or origin.
Entrainment: Occurs when rhythmic physiological or behavioral events match their period to that of an environmental oscillation; the interaction between circadian rhythms and the environment.
Diurnal: Daily, or of each day; from Latin dies (“day”) and diurnus (“daily”).
Master Clock: A pair of cell populations found in the hypothalamus, known as the suprachiasmatic nuclei (SCN); these cells contain the genes that govern circadian rhythms.
Mutant Gene: A permanent alteration in a DNA sequence that makes up a gene; used by chronobiologists to identify clock genes, by identifying the mutant gene on animals with arrhythmic circadian habits.
Picture a plant trying to perform photosynthesis at night: Without light, it’s a short drama. “Plants are dealing with life and death,” said Sally Yoo, assistant professor in the Biochemistry and Cell Biology Graduate Program at the University of Texas Health Science Center at Houston (UTHealth), somberly. “If they don’t follow circadian rhythms, they’ll die.” For humans, the prognosis would be slightly less bleak. “Even if you deleted the clock gene [an important gene regulating circadian rhythms], you wouldn’t die immediately,” Yoo said. “But you will suffer.” Likely problems? Constant psychological confusion and heightened risk for chronic disease, among other things. Life’s tough when everything’s out of sync.
Yoo’s colleague, Jake Chen, an associate professor in the same department, put it another way: “In our life, we say, ‘Timing is everything.’ But that’s an exaggeration. It is not, however, an exaggeration to say, ‘There is an optimal time for everything.’ In our body, it’s the same. Within individual cells and within each tissue or organ there’s a time for every physiological process. The circadian clock is the master mechanism, or timer, to make sure that everything runs smoothly and according to plan. That is a fundamental function.”
Chen and Yoo study circadian rhythms, the 24-hour physiological patterns that most organisms, including humans, follow each day. These rhythms are hardwired from millions of years of the world spinning around. The system is old, robust, flexible. It’s the product of an organism’s internal biological clocks and environmental cues — most notably, the sun, but also many other factors — which govern our behavior, hormone levels, sleep, body temperature and metabolism.
The so-called “master clock” governing human circadian rhythms is the suprachiasmatic nucleus (SCN), a pair of cell populations packed with genes that carry out this function (including Clock, Npas2, Bmal, Per1, Per2, Per3, Cry1, and Cry2), located in the hypothalamus portion of the brain. While molecular clock genes also exist elsewhere — the kidney, liver, pancreas, muscles, so on — the SCN acts as the chief executive officer, instructing the rest of the body to stay on schedule and figuring out how to incorporate cues from the environment. (For a brief digression, see how exactly the SCN works in an interactive feature by The Howard Hughes Medical Institute.)
As we’ll discuss later, being good to our natural rhythms improves daily physiological and psychological function — and ultimately short- and long-term health. Reducing the wear and tear on the clock keeps it fresh, maintaining what Yoo called “a robust clock” later in life. Chen was even more emphatic:
“I cannot emphasize enough how important the circadian rhythm is for prevention of chronic diseases,” he said. “And for long term benefits toward healthspan and eventually lifespan.”
About the Experts
Scientist: Zheng “Jake” Chen
Education: Ph.D., Columbia University, NY, Postdoctoral Fellow, The University of Texas Southwestern, Dallas, TX
Role: Associate Professor, Biochemistry and Cell Biology Graduate Program, University of Texas Health Science Center at Houston
Recent Paper: The small molecule Nobiletin targets the molecular oscillator to enhance circadian rhythms and protect against metabolic syndrome.
Area of Study: Small molecule probes for chronobiology and medicine.
Scientist: Seung-Hee “Sally” Yoo
Education: Ph.D., Korea Advanced Institute of Science and Technology
Role: Assistant Professor, Biochemistry and Cell Biology Graduate Program, University of Texas Health Science Center at Houston
Recent Paper: Period2 3′-UTR and microRNA-24 regulate circadian rhythms by repressing PERIOD2 protein accumulation. Also, Development and Therapeutic Potential of Small-Molecule Modulators of Circadian Systems.
Area of Study: Fundamental cellular mechanisms in circadian rhythms and deciphering physiological and pathological roles of the clock.
The History: Establishing the Fundamental Biology of Circadian Rhythms
The first thing to know about the study of circadian rhythms, also known as chronobiology, is that with few exceptions all organisms on the planet follow a circadian clock. From daffodils to sparrows, zebras to humans, everything under the sun follows the pattern of the sun. In 1729, French scientist Jean-Jacques d’Ortous de Mairan recorded the first observation of an endogenous, or built-in, circadian oscillation in the leaves of the plant Mimosa pudica. Even in total darkness, the plant continued its daily rhythms. This led to the conclusion that the plant was not simply relying on external cues, or zeitgebers, but also its own internal biological clock.
Two hundred years later, in the mid-20th century, the world of modern chronobiology blossomed. The field benefitted from contributions from a number of scientists, notably Colin Pittendrigh, the “father of the biological clock.” Pittendrigh studied the fruit fly Drosophila and shed light on how circadian rhythms entrain, or synchronize, to light-dark cycles. Jürgen Aschoff, a friend of Pittendrigh, also studied entrainment modeling, although they reached different conclusions about the manner in which entrainment occurs (parametric versus non-parametric, which you can read more about here and here). John Woodland Hastings and his lab also made important foundational discoveries about the role of light in circadian rhythms by studying luminescent dinoflagellates, a type of plankton. Erwin Bünning, who studied plant biology, also contributed foundational research in entrainment modeling, describing the relationship between organisms and light-dark cycles.
The next phase of chronobiology discovery began to articulate the specific molecular and genetic mechanisms of circadian rhythms. This came from the work of Ron Konopka and Seymour Benzer, who in the early 1970s aimed to identify specific genes that controlled the circadian rhythms in fruit flies. Konopka and Benzer are credited with discovering that a mutated gene, which they called period, disrupted the circadian clocks of the flies. This was the first discovered genetic determinant of behavioral rhythms. Jeffrey C. Hall, Michael Rosbash and Michael W. Young expanded Konopka and Benzer’s work by successfully showing how the period gene worked on the molecular level. Hall, Rosbash and Young — who were awarded the 2017 Nobel Prize in Physiology or Medicine — isolated the period gene, and then showed how the clock system worked on a molecular level.
Jumping from fruit flies to mice, Joseph Takahashi and his team discovered the mammalian clock gene in 1994 — appropriately dubbed clock — and characterized it as an “evolutionarily conserved feature of the circadian clock mechanism.” This gene discovery, along with the body of work by Hall, Rosbash, Young and the scientist Michael Greenberg, led to a watershed in chronobiological knowledge. Within a few years, the genes informing circadian rhythms in lower organisms were largely worked out.
Things have progressed steadily ever since, and, many of the findings in fruit flies and mice have shown remarkable conservation across species, meaning that there are analogous circadian genes that control the rhythms of more complex animals, including humans.
“The rising and the setting of the sun is still the primary influence on circadian rhythms, but other systems have steadily grown in scientific inquiry.”
The Current Research: Articulating the Role of Circadian Rhythms in Human Health and Disease
It’s important to note that the biology of circadian rhythms is incredibly complex — there are multiple scientific journals dedicated to the field of research — and as a result our understanding of the role biological clocks play in health is mostly a result of animal studies and human epidemiological studies. The experiments in lower organisms help articulate the molecular and genetic mechanisms at play, and then scientists can look at, say, how sleep disruption leads to increased incidence of type 2 diabetes, obesity, and cardiovascular disease.
Indeed, one area of study that’s especially promising is sleep. Scientists are now implicating a lack of sleep and the consequent disruption of circadian rhythms in the development obesity and depression, as well as most chronic diseases. Studies even show that a lack of sleep may have unexpected side-effects like not being able to read facial expressions.
The understanding of how circadian rhythms work has also expanded well beyond interaction with the light-dark cycle. “We have social cues, eating cues, and exercise or activity cues — it’s very diverse,” Yoo said. The rising and the setting of the sun is still the primary influence on circadian rhythms, but other systems have steadily grown in scientific inquiry. A large body of work has demonstrated that diet is a key extrinsic cue interacting with the intrinsic clocks, including Dr. Satchidananda Panda’s work on time-restricted feeding, or how the time of eating impacts health. (Endpoints covered Panda’s research at length, which you can read in The Complete Guide to the Science of Fasting.)
Overall, it is now clear that circadian rhythms perform a systemic role to orchestrate all aspects of physiology in our body, including vital organ functions, metabolism, immunity, cognition and more. Yoo’s research has been expanding the field, partnering with a chronic pain specialist to study the rhythms of pain in patients. Work is also being conducted on the role of the light-dark cycle and disruptions in circadian rhythms by jet lag on cancer growth. Such studies of circadian rhythms under normal and disease conditions are teaching us important new insights that can be harnessed for lifestyle changes (when to eat, how much to sleep) and for discovering drugs that can help modulate circadian rhythms. And there is plenty more research to be done in virtually all aspects of human health and disease.