Guide to Circadian Rhythms / History

From: The Complete Guide to the Science of Circadian Rhythms

see also: https://www.circadiansleepdisorders.org/defs.php

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https://endpoints.elysiumhealth.com/

Two leading scientists explain how circadian rhythms work and offer advice on lifestyle changes to improve your health
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. (WOW!)

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.

Sleep

The most important thing you can do is keep your sleep and waking times consistent and get enough sleep — seven to nine hours is usually considered the right amount for adults. At this point the scientific research on not getting enough sleep or having disruptive sleep is conclusive: It has a negative impact on mood, focus, cognitive function, and ultimately is linked to chronic disease. What’s more some scientists suggest that circadian misalignment caused by social jet lag may be a widespread phenomenon in the western world contributing to health problems.

So when should you sleep? Typically the body begins to secrete melatonin around 9:00 p.m. This is the trigger to shut things down and go rest. Melatonin secretion ends around 7:30 a.m., and during the day, there is virtually no melatonin in the system. Working around that general window, adjusting for personal preferences based on your natural inclinations, is key for avoiding sleep fragmentation (waking throughout your sleep) and for maintaining optimal health.

Finally, light is a factor. The light-dark cycle no longer is the only influence on our system, since we now encounter artificial light constantly — but it still plays a primary role. Getting plenty of natural light early in the day and avoiding unnatural light (blue light from screens, for instance) in the evening will support circadian alignment.

A huge topic; one that I think will turn out to be extremely enlightening in the “mystery” of Asperger types… 

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