Signs of Winter 2: Circadian Rythms

Photo by jonathunder, Wikimedia Commons

This year’s Nobel Prize in Physiology or Medicine went to three scientists who have explored the fundamental genetics and physiology of living organisms’ biological clocks. Over the past three decades these researchers have put together an incredibly compelling picture that explains how each and every cell inside an organism is able to “know” what time it is!

A gene in fruit flies was the start of it all. This gene was found to encode for a protein that is synthesized in a cell during the night and then broken down in that same cell during the day. The concentrations of this protein, then, is an exquisitely sensitive index of the time of day. There was, though, much more to this. Three genes (and three proteins) were found to interact in ways that allowed an organism to not only modify their own day/night cycle but also stretch or shrink their cycle to fit patterns greater than or less than the typical 24 hour day period. Further, these “clock proteins” are intertwined with the other signaling and controlling proteins of a cell and, thus, have great influences on the activities of almost all aspects of a cell’s metabolism.

The science of Circadian Biology has grown out of the groundbreaking work of these new Nobel Laureates. Circadian Biology studies the physiological consequences of the changing “clock proteins” on the metabolic processes of an organism.

Figure by Yassim Mrabet, Wikimedia Commons

For example, in a 24-hour period there are times when your conscious neurons are working most efficiently (increased alertness, faster reaction times). This period of time is related to circadian regulation. Also, there are times when your immune system is operating more efficiently, when your blood pressure is typically on the rise, when your heart is under its maximum daily stress, when your muscles are controlled in the most coordinated way they can be, when you generate a maximum daily body heat and when you generate your minimum amount of daily body heat. There is also a time when you readily make melatonin (and are, thus, able to naturally fall asleep) and other times when a variety of hormones are being synthesized.

A practical application of Circadian Biology is “chronotherapy.” Chronotherapy explores the body’s response to different stresses or treatments at different times of day. For example, a study in England demonstrated that individuals who received their flu shots in the morning (the time when immune responses are most robust) made more anti-flu antibodies than those individuals who received their flu shots in the afternoon. Also, short-term control of serum cholesterol can be achieved via drugs that slow down the critical rate controlling liver enzyme for cholesterol’s synthesis. It turns out that that enzyme is maximally functional at night, and if the inhibitory medication is also taken at night (say right before bed) it is much more effective in reducing cholesterol levels.

Chemotherapies timed to the circadian biology of the tumor cells are not only more effective but also have fewer side effects. Anti-histamines and inhaled corticosteroids designed to control allergies and asthma are also more effective when they are taken at night when the circadian rhythms of the affected cells are at their maximum states of activity.

A common set of drugs designed to reduce arterial blood pressure are angiotensin-2 receptor blockers. Blocking these receptors causes an overall vasodilation (volume increase) in the body’s arteries which reduces the overall pressure of the system. These angiotensin receptors, though, operate cyclically under circadian control. They are most active at night! Taking the angiotensin-2 receptor blockers at night, then, is the most effective way to use this medication to achieve blood pressure control.

Photo by Ion Chibzii, Wikimedia Commons

An October 26, 2017 article in the British medical journal The Lancet described data from almost six hundred open heart surgeries conducted at Lille University Hospital (Lille, France). These data showed greatly improved patient outcomes when the surgeries were conducted in the afternoon rather than in the morning. There was, according to this study, a 50% lower risk of heart failure or other cardiac event in the afternoon surgeries! The heart muscle itself was more resilient and quicker to regain its ability to contract after these afternoon surgeries, and there were 287 circadian rhythm genes operating at different levels between the morning surgery and the afternoon surgery heart muscle samples.

Back in 2015 (Signs of fall 12: Seasonal Jet Lag (Nov. 12, 2015)) I wrote about the impacts of the time change from Daylight Savings to Standard Time. People do get a little off: accidents go up, hospitalizations go up, productivity at work goes down. The chances, though, that our “human society time” means anything at all to the plants and animals around us are pretty small. We have recently seen the effects of the shortening day length on the leaf biology of our senescing deciduous trees and on the behaviors of many of our birds who were compelled to fatten up and fly south. They really don’t care if sunrise is at 6:55 am (Standard time) or 7:55 am (Daylight time): they just care that there are 10 hours and 17 minutes (and falling!) of daylight in the 24 hour period! We will get down, by the way, to 9 hours and 16 minutes of daylight on December 21 (5 hours and 47 minutes less daylight than back on the June Solstice), and then we will start it all over again!

Photo by D. Sillman

Any animals that are tied in to human activity patterns, though, are sure to notice that something has changed when Standard Time returns. My front yard crows have come to expect their morning pile of peanuts to be out there when they arrive a little after dawn. My wild turkeys have timed their appearance in the front yard bird feeder area to coincide with no human presence (I walk Izzy between 6:30 and 7:30 am, and Deborah leaves for work around 8. The turkeys usually roll in around 8:30, which on Day #1 of this Fall’s Standard Time, was 7:30 (right when I was out with Izzy). They were pretty startled by our presence! I hope that they come back!). Izzy, herself, is not sure what to think about the un-naturalness of this time change either. She is used to having her supper at 4:30 pm. Her “biological” supper time is an hour out of phase with this new Standard Supper Time. She is staring at me right now: 3:35 pm. I hope her circadian rhythms adjust soon!

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