The Evolution of Circadian Biology

Life on Earth creates order from entropy, playing out like a coherent melody from the disorder of many sounds. This coherence is made possible by a set tempo, allowing all parts to play in harmony. The tempo for life's song is created by the spin of our planet, completing a full rotation approximately every 24 hours. Earth’s spin creates predictable cycles of day and night as any given point on the planet’s surface turns towards and away from the Sun’s electromagnetic energy.

Daily changes in the availability of sunlight not only create day and night but also influence temperature and moisture levels in the environment. To function and survive amid these changing conditions, organisms must maintain homeostasis, which is the ability to keep a stable internal environment despite external fluctuations. If organisms only reacted to environmental changes as they occurred, they wouldn't have enough time to prepare internally. Therefore, having a mechanism for predictive adaptation, such as an internal clock, would enable living organisms to anticipate cyclic changes in the environment and achieve homeostasis.

If you watched a sunflower all day and night, you’d see its leaves move to follow the Sun, maximizing photosynthesis. At night, you’d see its leaves droop and appear to sleep. In the early morning hours, before the Sun has even risen above the horizon, you’d observe the leaves perk up and orient to the East. The sunflower isn’t simply responding to sunlight; it actively anticipates its arrival and positions itself to best take advantage of the morning light. In the 18th century, scientists’ observations of certain plants’ behaviors and their heliotropism (tracking of the sun) suggested the presence of an internal biological clock. This groundwork led to the 2017 Nobel Prize in Physiology or Medicine being awarded to Jeffrey C. Hall, Michael Rosbash, and Michael W. Young for discovering clock genes and the molecular mechanisms controlling circadian rhythms.

Earth’s day-night cycle drove the evolution of clock genes in the cells of all living beings, from bacteria to plants and animals. These clock genes enable organisms to anticipate and adapt to daily changes in the environment and regulate physiological processes accordingly. This establishes our circadian rhythms – roughly 24-hour biological cycles that influence numerous physiological, behavioral, and metabolic functions. Like a metronome setting the tempo for a song, the rising and setting of the Sun sets the rhythm for life on Earth.

Circadian rhythms dictate our sleep-wake cycles, body temperature, metabolism, digestion, hormone release and regulation, neurotransmitter production, cellular regeneration, and more. Every cell in our body has a clock gene, and circadian programming determines when genes are turned on or off, initiating modes of activity or rest/rejuvenation. It is estimated that 70% of our genome is regulated by circadian signals, and this elucidates why circadian disruption caused by modern living conditions is so pathogenic.

Circadian systems are a predictive adaptation to the Earth’s 24-hour spin and its regular cycles of day and night. In addition to daily circadian rhythms, our biology is influenced by longer-term infradian rhythms from seasonal changes. We experience seasons because the Earth is tilted 23 degrees on its axis as it orbits the Sun. This axial tilt creates variations in the amount of sunlight each hemisphere receives throughout the year. During different parts of the Earth’s orbit, either the Northern or the Southern Hemisphere will be tilted toward the Sun, creating longer days in the summer and shorter days in the winter. This adds dynamics to life’s song, the tempo speeding up or slowing down based on the increased or decreased availability of light across the repeating seasons. Infradian rhythms, being biological patterns with cycles that last longer than a day, are critical for organisms’ abilities to regulate energy storage and metabolism across the changing seasons. Infradian rhythms determine cycles of hibernation, menstruation, migration, breeding, molting, and more.

Photoreception

Light is the primary zeitgeber, or time cue, for our circadian rhythms. Our bodies determine the time of day based on the specific wavelengths of light that are present in the environment. In order of decreasing wavelength, sunlight is comprised of invisible infrared light, the visible spectrum of red, orange, yellow, green, blue, and violet, and invisible ultraviolet light. The concentration of these wavelengths of light changes dynamically throughout the day as the Sun moves across the sky, providing a constant stream of information to our bodies on what activities to perform and when. Our photoreceptors – specialized cells that convert light signals into electrical signals – enable our ability to detect and respond to light. We are equipped with visual and non-visual photoreceptors, both of which are located in the retinae of our eyes while non-visual photoreceptors are also present in our skin.

The two main types of visual photoreceptors in our eyes are called rods and cones. Rods are responsible for low light vision and do not involve distinguishing color, while cones enable color vision and are active at higher light levels. We have three types of cones: S-cones for detecting short wavelength, blue light, M-cones for detecting medium wavelength, green light, and L-cones for detecting long wavelength, red light. Together these photoreceptors work to provide our ability to discern images and all the many colors we can see.  

Non-visual photoreceptors are not involved in forming images but play a crucial role in the detection of specific light frequencies in the environment. These cells contain photopigments such as neuropsin and melanopsin, which were both discovered in 1998. Neuropsin enables our bodies to detect the presence of high-energy ultraviolet light (particularly UVA), signaling pathways that stimulate the melanocytes in our skin to produce protective melanin. Melanopsin, found in photoreceptors called intrinsically photosensitive retinal ganglion cells (ipRGCs), is designed specifically to detect blue light and is critical for regulating our circadian rhythms.  

The ability to detect blue light (which is electromagnetic radiation with wavelengths ranging from 450 to 495 nanometers) is particularly important when it comes to circadian regulation and has been since the dawn of our species. Life on Earth first evolved in the oceans, where the depths are predominantly blue-lit environments. Other wavelengths of light are readily absorbed and scattered by the water, while blue light can penetrate deepest below the surface. Therefore, the only way to determine whether it was day or night, which would have been important for avoiding predators and regulating activities such feeding and reproducing, would be to evolve mechanisms for detecting blue light, such as melanopsin. These ancient evolutionary programs are still embedded in our biology today. Blue light remains the most significant driver of our circadian systems, or in the case of artificial blue light at night, the most significant disruptor.

The Body’s Master Clock

When photons of light enter the eye, photoreceptors in the retina convert the photonic energy (or light information) into electrical signals matched to the specific wavelengths of light in the environment. This process is similar to the way microphones capture sound waves and turn them into electronic signals for amplification or recording. The electrical signals converted by photoreceptors then travel down the retinohypothalamic tract to a cluster of nerves in the hypothalamus called the suprachiasmatic nucleus (SCN).

The SCN acts as the body’s master clock and central timekeeper, keeping the body’s systems coupled to the same sense of time and operating together. The SCN does this by distributing the light information to the various peripheral clocks located in organs and tissues throughout the body. Peripheral clocks include those located in the liver, heart, lungs, kidneys, pancreas, skeletal muscle, adipose tissue (fat), and gastrointestinal tract. The liver’s release of glucose into the bloodstream, the heart’s daily variations in blood pressure, the amount of cellular energy produced in our muscle tissues, the secretion of digestive enzymes in our gut, the release of insulin by our pancreas, the leptin secretion in our adipose tissues, and variations in respiration are all circadian-based activities that are instructed by light cues in our environment. 

The SCN is like the conductor of an orchestra – the different biological systems inside the body being the instruments. If each instrument played according to its own rhythm and tempo, the noise would create discord rather than a coherent melody. To create coherence, the instruments must follow the same sense of timing. The tempo has already been written by the Earth’s cosmic dance with the Sun, its 24-hour spin, 23-degree axial tilt, and 365-day orbit. It’s the SCN’s job to relay this information about the outside world to the complex internal world inside each of us.

Another helpful analogy for understanding the importance of circadian rhythms is to think of a healthy, functioning economy. If everyone operated according to their own sense of time, coordination would be impossible, leading to chaos, or in biological terms, inflammation. It doesn’t matter how many commodities, like food and nutrients, are available if there is no ability to synchronize economic activities. This is like the hundreds of thousands of biochemical reactions occurring inside the body that rely on synchronized circadian rhythms.

The Balance of Light and Darkness

Light and darkness are crucial partners in regulating our circadian biology, akin to the balance of yin and yang. The gradual increase of blue light in the morning signals the brain to activate the pituitary gland, our body’s internal compound pharmacy. This gland releases stress hormones such as cortisol to wake us up and kickstart our day, raising blood sugar levels to ensure adequate energy. As the sun sets, the diminishing blue light signals the brain to halt cortisol production, lower blood sugar levels, and begin melatonin release from the pineal gland for restorative sleep.

The pituitary gland, reflecting dynamic yang energy, is stimulated by daylight and governs hormonal responses that promote activity and energy expenditure, including thyroid and adrenal functions. Conversely, the pineal gland, embodying restorative yin energy, produces melatonin at night in the absence of light. Proper darkness, free from artificial blue light, is essential for our circadian system. Melatonin not only induces sleep but also acts as a critical antioxidant, facilitating autophagy and apoptosis. Autophagy recycles damaged cell parts, and apoptosis removes irreparably damaged cells to prevent tumors. This is why impaired melatonin production, due to exposure to artificial blue light at night, is associated with an increased risk of various cancers. Despite the requirements of our biology, in today’s world, we’ve nearly eliminated darkness, lighting up our skies at night with artificial electric light. The decision to alter our environment this way disrupts the circadian balance of all living beings on the planet, and the evolutionary conditions under which they evolved.

Clinical Implications of Circadian Disruption in the Modern World

Our circadian biology evolved over the course of millennia under the conditions of natural sunlight and Earth’s day-night cycle. We are biologically attuned for brighter days and darker nights. For most of our history, the only light at night available to us was the moon’s reflected sunlight or fire, which exhibits a light spectrum characterized by high levels of red and infrared and very low levels of melatonin-disrupting blue light. However, in 1879, the evolutionary trajectory of our species changed suddenly with the invention of electric light. In less than 150 years, we have completely altered our epigenetic light environment, as our technology advanced far more rapidly than our biology can adapt.

The ability to brighten our nights when our bodies expect darkness isn’t the only factor that disrupts our circadian programming. The type of light matters greatly. Initially, the widespread use of incandescent light bulbs carried far fewer negative health implications. This is because incandescent light bulbs are a thermal source of light that emit a light spectrum similar to fire, with more than 80% restorative infrared light and very low levels of stimulatory blue light. Fluorescent lights then made their debut in 1939, with a very alien, uneven light signature that eliminated infrared and exhibited sharp spikes in the visible spectrum. By 2008, LEDs (light emitting diodes) with zero infrared and a sharp spike in blue light began to dominate the market.

Unlike our LEDs, in nature, blue light is never present without a balance of infrared wavelengths. There are biological consequences to isolating specific frequencies of light and eliminating others. Unfortunately, we do this in the name of energy or economic efficiency while ignoring the negative implications on human and environmental health. We now spend most of our time indoors, out of sunlight, exposed to artificial light emitted our light bulbs, phones, computer screens, and televisions.

Our artificial lights are enriched with blue light, which is the wavelength of light that activates our melanopsin receptors and entrains our circadian rhythms. While the wavelengths of natural sunlight are dynamic and ever shifting throughout the day, artificial lights remain static, constantly signaling to the brain that it is midday. The brain responds by suppressing melatonin, stimulating the release of cortisol and dopamine, raising blood-sugar levels, and dampening metabolism. This unrelenting stimulation can contribute to disrupted sleep patterns, inhibited cellular repair due to melatonin suppression, adrenal fatigue from constant cortisol secretion, metabolic dysfunction and obesity from increased blood glucose, and attention deficit disorders and addictive behaviors due to dopamine depletion. This is why shift workers, with disrupted circadian rhythms and excessive exposure to artificial light, have a higher risk of developing type 2 diabetes. This is also why the fluorescent lighting in our schools (in addition to their high flicker rate) negatively affects our children’s health and ability to concentrate.  

Circadian disruption is increasingly recognized as a significant factor in the epidemic of chronic diseases which plague society today, and which were not prevalent 150 years ago. Mounting evidence links circadian disruption to many diseases, including cancer, diabetes, hypertension, neurodegenerative, neurodevelopmental, autoimmune, metabolic, gastrointestinal, mood, and reproductive disorders. This is evident by searching any of these conditions alongside the term “circadian” in PubMed, the National Library of Medicine’s database of biomedical literature. Excessive and/or poorly timed exposure to artificial light sends chaotic and confusing signals to our cells about where they are in time, creating decoherence and inflammation in the body. The symphony decouples from the rhythm of the cosmos, the melody gets muddled, and we begin exhibiting symptoms of chronic illness.

Circadian Optimization Strategies

Reestablishing a connection to Earth’s day-night cycle and supporting our circadian biology helps to optimize our immune function, metabolism, endocrine health, brain function, and cellular repair. For most people, our days are too dark, and our nights are too bright. The goal, then, is to increase our exposure to healthy light and decrease our exposure to unhealthy light.

•  Sunrise: Circadian entrainment begins with seeing low-angular morning sunlight. Seeing the sunrise sets the SCN (the body’s master clock) each day. However, the light should enter your eyes directly without the intervention of windows, contacts, or glasses that filter specific frequencies of light. Morning sunlight should be the first light you see, before looking at your phone screen. This is because the phone will emit high levels of blue light that skips the early morning signaling and spikes cortisol levels unnaturally.

• UVA Rise: Following sunrise, seeing UVA rise (typically when the Sun has risen about ten degrees above the horizon) is beneficial because UVA light through the eyes stimulates the transformation of tryptophan into serotonin, the precursor for melatonin. This means to build ample stores of melatonin for rejuvenating sleep at night, it’s important to get enough sunlight exposure during the day.

• Circadian Meal Timing: Food is a secondary zeitgeber for circadian rhythms, and this is why it’s a best practice to eat within a circadian meal window. This means eating only during daytime hours, starting with breakfast within 90 minutes of waking and finishing your last meal around sunset or three to four hours before bed.  

• Sun Breaks: As most people work indoors under artificial light, taking regular short breaks to expose your eyes to natural sunlight helps keep the SCN informed of the time of day so that it can regulate the body’s peripheral clocks. Cracking open a window also helps by letting in the sun’s balanced light spectrum, as closed windows create conditions that are disproportionately high in blue light and lacking in infrared.  

• Blocking Blue Light at Night: After sunset, it’s important to mitigate exposure to artificial blue light, which disrupts melatonin release. This can be achieved using several strategies, such as wearing orange or red-tinted blue blocker glasses, using floor-level lamps with incandescent bulbs rather than overhead LED lights, limiting screen time, turning on color filters on your devices, and creating a dark sleeping environment.

Following these strategies will shift your internal clock, day by day, to realign with the patterns of the natural world from which we evolved and with which we remain a part. With all internal systems coupled to the same sense of time, knowing where the Sun is in the sky, and playing together in harmony, we can improve our health and mitigate the 21st century circadian health crisis.