Circadian Biological Disarray – A Common Thread For All Disease.
We live by the clock. Stop and think about all the clocks that make our lives tick, from the alarm clock that gets us up in the morning to the thermostat that warms our homes and the internal clocks that run our cell phones and computers. Every little gadget, device, and smart appliance, along with the car we drive, literally depends on internal clocks. Our 24/7 world—from work to pleasure—is governed by timekeepers.
Now scientists are discovering that we’re not the only ones run by clocks. The whole living world has built-in clocks to keep its systems on schedule, from humans and animals to plants and single cells. Even at the chromosome level, genes are turned off and on by sophisticated clocks.
This dependence on the 24-hour cycle of day and night should not surprise us. Genesis’ account of creation emphasizes that this cycle began on day one, even before God created the sun and planets. “
And God said, ‘Let there be light,’ and there was light. And . . . God separated the light from the darkness. God called the light Day, and the darkness he called Night. And there was evening and there was morning, the first day” (Genesis 1:3–5).
The Rhythm of Life
Since ancient times, human beings have recognized that our lives sync with this cycle, as we grow tired or hungry at predictable times. But it wasn’t until a few decades ago that scientists began exploring how our body’s systems are specifically designed at a molecular level to interface with the cycle of light and dark.
This special system is called a circadian rhythm or clock. (The word circadian comes from the Latin circa, meaning “around” as in a circular cycle, and the Latin word for “day,” diem.)
Increasing interest in this clock in the 1960s opened a whole new field of biology known as chronobiology (the timing of biological activity). This field of research continues to revolutionize how we understand all of life and human health. Medicines for common conditions like diabetes and weight loss are profoundly affected by the time of day they’re taken. In recognition of major research advances in this field, the 2017 Nobel Prize in Physiology or Medicine (yes, that’s its official name) was awarded to three scientists who discovered “the molecular mechanisms controlling the circadian rhythm.”
We now know that nearly every living thing on the planet, including plants, animals, fungi, and even single-celled photosynthetic bacteria, has this amazing ability to track the course of the day-night cycle—with an accuracy down to minutes. Life on earth could not exist without this ability to adjust its processes and systems with the day-night cycle. It governs when cells grow, metabolize, reproduce, and so on, to take full advantage of peak times of solar energy and down times of total darkness.
Plants are an obvious example. They photosynthesize and make carbohydrates during the day, and then at night they metabolize the food they made earlier that day to grow new leaves, stems, and roots. Even humans have basic processes that depend on whether we are awake or sleeping. At night, for instance, the body increases its output of growth hormones; this is when your skin cells regenerate, muscles repair damage, and kids grow.
Sophisticated man-made machines, such as computers, cars, and smart appliances, are a good analogy to help us understand how central clocks or “oscillators” must oversee complex systems. These machines need integrated clocks so they can follow instructions, coordinate with other system components, and track and respond to changing inputs and conditions. But they don’t begin to compare to the circadian clocks in living organisms.
The Body’s Master Clock
When it’s time to translate one of those glorious, sun-filled mornings into a wake-up call that gets your body in gear for another day’s activities, your central master clock swings into action. The all-important timekeeper is located inside a region of your brain called the hypothalamus. Not by accident, this clock is ingeniously positioned directly above the intersection between the two optical nerves coming from your eyes—the ultimate light sensors.
This timekeeping computer, nestled inside the hypothalamus, consists of a small cluster of about 20,000 neuron cells and is called the suprachiasmatic nucleus. It’s the headquarters that commands a wide array of nerves and hormones to regulate many body functions over 24 hours. Other parts of your brain and many organs throughout your body wait for a bugle call from the suprachiasmatic nucleus to get the day started.
Your Body Has Many Clocks
But this central body clock is just the beginning of the amazing story. Humans, mice, and various animals not only have a centrally located master clock in their brains, but they also have many secondary (or “peripheral”) local clocks that run the different organs, tissues, and individual cells throughout their bodies. Moreover, just as a connected network of computers keep their times synced with a central server, the systems in your body keep their operations in perfect sync with the brain’s central clock. This amazing designed cellular communication unifies all the body parts and tissues in a systems-critical, time-based context.
Researchers are just beginning to unravel the indescribable complexity required to pull this off, and they are thoroughly amazed at what they are finding. In fact, scientists have now looked at many different tissues, including the kidneys, liver, and intestines, and in nearly every case they have found an independent clock that also takes cues from the hypothalamus.
As it turns out, almost every cell in the human body has a circadian clock. This enables each cell to figure out when to use energy, when to rest, when to make repairs, or when to divide and make more cells. For example, your body’s hair cells divide at a particular time every evening (which means your hair grows mostly at night).
Discovering Clock Genes
The daily cycle in animals and plants has fascinated people for hundreds of years, but it was only about 50 years ago that scientists started investigating the underlying biochemistry in earnest. At an important meeting in 1960, scientists at the famous genetics lab in New York called Cold Spring Harbor brainstormed about what genetic and molecular processes might underlie circadian rhythms, and they developed experiments to test their theories.
The key circadian clock research was identifying creatures with abnormal daily cycles, such as mutant yeast cells, fruit flies, and mice. By comparing their genes and biology to their normal counterpart creatures during a 24-hour rhythm, they could discover which genes are involved (because they’re messed up in the mutants). The biological revolution in the early 1970s, which opened the door to DNA studies, provided the new tools to unravel this mystery.
Among the most helpful lab subjects were fruit flies that had out-of-whack daily cycles (either 19 or 28 hours) or no discernible rhythm at all. Research in the humble fruit fly led circadian cycle researchers to discover that a mutation in one of its genes was behind this abnormality. They cleverly named this gene PERIOD in 1971. The PERIOD gene was later found to produce proteins at different rates over the course of the day.
Interestingly, the lab workers discovered this variation in gene activity because they did their experiments at different times of day depending on their own aberrant circadian rhythms—some were early risers while others were night owls when they took their measurements.
Other fruit fly genes with similarly creative names soon followed, like CYCLE, CLOCK, and TIMELESS. As it turned out, all these genes play a role in regulating the cell’s processes on a 24-hour cycle. They produce proteins, called transcription factors, that act like master switches turning other genes on and off in a highly coordinated, time-sensitive process.
In addition to serving as genetic switches, a number of these clock regulator proteins are so amazingly engineered by an all-powerful Creator that they can also respond to light. Some cells that have been cultured and studied in the laboratory respond to the intensity of light or even the quality or wavelength of light (such as blue light, in particular). The cells are photoreceptors called Melanopsin. (https://en.wikipedia.org/wiki/Melanopsin)
Circadian Clocks and Your Health
What does all that mean for us? Circadian clocks are critical for good health. One of the most familiar examples is jet lag. If you fly from California (Pacific time) to Virginia (Eastern time), you lose three hours in your normal schedule. When your alarm clock says it’s 8:00 the next morning, your circadian clock says it’s 5:00. Eventually, your circadian clock will adjust to the local time because of your amazing sensory and response systems in play, but it will take several days.
But scientists are coming to realize that our modern age is creating all sorts of other difficulties that our pre-jet-age ancestors never faced. Blue lights glowing on computer screens late at night, fast food available at the snap of a finger 24 hours per day—such modern conveniences are contributing to health conditions we never had before.
By improving our understanding of circadian rhythms, scientists hope to find better treatments for sleep disorders, weight management, good mental health, and even better learning. (Yes, that’s right, most people have an optimum time when they learn best.)
Consider household lighting and the light coming from the electronic devices that we view at night just before we go to bed. It appears that our body clocks are especially designed to respond to a special wavelength in the visible light spectrum called blue light. Blue wavelengths are beneficial during normal daylight hours, boosting mood, attention, and even reaction times. Viewing electronic screens late at night, however, zaps you with blue light, confusing your body into thinking it’s high noon. This can severely reduce your ability to sleep, get you off schedule, and lead to a variety of health problems.
Think about it—the human body has trillions of cells, each with its own clock, yet they constantly interact with the other cells in their organ, while they also take cues from the main clock in the brain (SCN). The amount of synergistic coordination and engineering boggles the mind.
The magnitude of interconnectivity and system complexity among living creatures remains a daunting challenge for human researchers to understand and untangle, even with modern tools of molecular biology and genetics. Yet many scientists declare with unflinching certainty that they arose from the random, gradualistic processes of evolution.
How much more intellectually satisfying it is to view these interdependent systems as prime examples of irreducible complexity. The myriad, complex components of the circadian clock system had to be in place from the very beginning for it to work, and it could never have come about any other way.
There Is A Clock For That
- Brain: The brain links the body’s sleep-wake cycle to the day-night cycle. The brain is most alert around 10:00 a.m. and sinks into the deepest sleep around 2:00 a.m.
- Pineal Gland: The body secretes the hormone melatonin at night to help us sleep and it stops around 7:30 a.m.
- Lungs: Lungs are most prepared to fight disease at the most active hours (and are most prone to asthma at night).
- Heart: Blood pressure rises most sharply early in the morning (around 6:45 a.m.) to get the day started. Blood pressure peaks around 6:30 p.m.
- Liver: The liver is most active during what it expects to be the most active times of the day, as it regulates cell growth, produces bile (to digest fat), and removes toxins based on the time of day.
- Adrenal Complex: The “stress hormone” (cortisol) increases in the early morning to help you wake up.
- Stomach: Eating at odd times, such as late at night, may cause weight gain because relevant organs aren’t prepared to deal with the food.
- Pancreas: The pancreas regulates the production of insulin (a hormone that regulates blood sugar). A clock that is out of sync with the master clock can lead to diabetes.
- Muscle: Muscle takes the largest amount of glucose from the blood (a sugar used for energy) around 5:00 p.m. to maximize muscle strength.
- Skin Cells: Wounds heal twice as fast during the day because skin cells for healing (fibroblasts) turn off at night.
- Body Fat: Our body fat has a clock. If it gets out of whack, it can contribute to obesity. Body temperature (a key marker of circadian rhythm) drops to its lowest around 4:30 a.m. and rises to the highest around 7 p.m.