In this blog you will learn:
- Why the biological clock is the conductor of your entire body.
- How light, nutrition, and exercise synchronize your internal clocks.
- What role your eyes, skin, intestines, and lungs play as timekeepers.
- Why incorrect timing lays the foundation for fatigue and illness.
We have a central master clock in our brain, and every organ and even every cell in your body also has its own clock mechanism. The better these clocks are synchronized with each other and with ‘natural stimuli’ from your local environment, the healthier you will live.
The biological clock is regulated internally but influenced externally. Especially by light and darkness. It is an interdynamic play between time-givers, regulators, and observers. How do these clock mechanisms work in our brain, organs, and cells? Why is a well-functioning and synchronized biological clock so fundamental to health?
The whole of timing mechanisms in our brain, organs, and cells is called the biological clock. The biological clock operates on a so-called circadian rhythm. Circa is Latin for ‘around’ and dia comes from ‘diem’, meaning day. Together, it means: around the day. Circadian rhythms are biological processes that run on a daily rhythm, or 24 hours. For example, you can imagine that you need to be more alert during the day (cortisol needs to go up) than at night (cortisol needs to go down).
The word rhythm may sound innocent, but it is a fundamental basis for a healthy functioning body. Unfortunately, it is still too little recognized and applied in modern medicine. This is despite the fact that science is clear: a vast range of modern diseases has a strong associative or causal link with a disruption of biological rhythms.
The biological clock (with its circadian rhythms) controls, regulates, and influences everything. From hormone release to immune function to cell repair to energy metabolism and gene expression, to body temperature, bowel movements, gut bacteria quality, cardiac function, organ function, fat burning, inflammation, embryonic development, blood circulation, cognitive performance, metabolism, nutrient absorption, sleep quality and much much more.
It not only determines when a process occurs but also the quality of that process.
Normal and disrupted circadian control of bowel movements in the gastrointestinal tract. Duboc, H., Coffin, B., & Siproudhis, L. (2020). Disruption of circadian rhythms and gut motility: An overview of underlying mechanisms and associated pathologies. PMID: 32134798.
Conducting the Orchestra
Imagine all these body functions are musicians with musical instruments, then the biological clock is the conductor. Without guidance, the music and interaction between the instruments in the orchestra do not go well. If your body has to chronically listen to false notes (inflammations) because the conductor is often out of tune (disruption of the biological clock), the instruments will eventually break down (health complaints).
Then the symphony of life becomes more bitter than sweet.
Every animal, plant, andeven bacteria function on a biological clock with circadian rhythms, and so does the human being.
A well-functioning biological clock depends on time-givers, time regulators, and timekeepers. Especially the interaction between these three.
First of all, what are time-givers?
Time-givers: light, nutrition, exercise, and more
Although the biological clock is self-regulating, it continuously needs synchronization with external factors to function well. These external factors are called time-givers. Time-givers (or Zeitgebers) are external stimuli that your body receives and pass information to the biological clock. With that information, the biological clock controls certain processes, such as hormone release, gene expression, repair, or growth factors.
The time-givers are sunlight, temperature, nutrition, exercise,electromagnetic fields and evensocial routines (such as work, hobbies, and interactions with others). Timing is essential here. The timing of light you receive during the day determines how well your biological clock functions. Are you outside around sunrise (good timing) or are you still in bed at that moment (bad timing)?
Timing and Type
Having the right timing alone is not enough. Also, the type of time-giver is essential.
For example, have you woken up around sunrise, but are you standing under a bright LED lamp in the bathroom for the first half hour or scrolling on your phone for fifteen minutes? Then your timing is right (you woke up around sunrise), but the type of light is dramatic, doing more harm than good to your biological clock. The same applies to nutrition. Do you eat your meals when it is still light outside (good timing) or do you have a meal when the sun has already set three hours ago (bad timing)? Do you eat a lot of fats and proteins in January (the right type for winter) or do you eat a carbohydrate-rich diet throughout the winter (bad type)?
Synchronization between the central and peripheral clocks occurs when there is sufficient natural light during the day, meals are eaten during the day, and we sleep at night. This ensures a good alignment of internal biological rhythms. On the other hand, when there is light in the evening or at night, or when eating and sleeping are not in line with the biological night, the clocks become out of sync. This can lead to disruptions in metabolism and other bodily problems. Poggiogalle, E., Jamshed, H., & Peterson, C. M. (2017). Circadian regulation of glucose, lipid, and energy metabolism in humans. Metabolism, 78, 1-11.
Timing and type say something about context, and context is key in circadian biology (the field that studies the biological clock and circadian rhythms). Do you do an intense crossfit workout at 7 AM under bright artificial light while the sun has not yet risen? Or do you do the same workout in the afternoon in an outdoor gym under natural daylight, when generally body temperature, muscle strength,blood pressure and energy efficiency of your mitochondria (the energy engines of your cells) are more optimal?
The same workouts with completely different contexts can have a completely different effect on the functioning of your biological clock.
Thus, on your health.
With the right timing and type of time-givers, you can literally synchronize the clocks, so that cells and organs function better and are better aligned with each other. Like a well-run orchestra with a conductor who seamlessly directs everything. Incorrect timing and type of a certain time-giver can significantly disrupt the circadian system and deregulate clocks, with the result that disease lurks.
Let’s get a bit more technical and zoom in on the regulators.
Time Regulators: Clock Levels and Clock Genes
Our body has 3 types of clock levels: the master clock, organ clocks (or peripheral clocks), and cellular clocks. All these clocks are governed by clock genes. A clock gene is literally a protein structure that instructs a cell on what to do at what time, for example, the production or inhibition of hormones, when the cell should repair itself, or initiate an inflammatory response. About 10 to 15% of all genes in our body are clock genes. This fact alone underscores the enormous importance of the biological clock in health.
Clock genes are simply put time regulators because they regulate at what times of the day certain processes occur or certain other genes are turned on or off.
Back to the 3 clock levels. Let’s focus on the master clock.
The Supra…What?
A difficult word you can immediately forget is the suprachiasmatic nucleus (SCN is easier to remember). The SCN is the master clock in our brain and is located just behind your eyes. It consists of 20,000 nerve cells that are compactly packed together.
It is the clock that also controls the organ clocks and cellular clocks and thus regulates the total coordination of the circadian system. The SCN sends signals (via hormones and nerve impulses) to cellular clocks in organs and tissues to synchronize them with the day-night cycle.
The SCN receives light information through the eyes and is directly connected to your central brain area, where the hypothalamus, pituitary gland, habenula, and pineal gland are located. This brain area produces hormones (such as melatonin) and neurotransmitters (such as dopamine), regulates temperature, determines your mood and emotional state, activates or deactivates stress, and controls the autonomic nervous system.
If SCN tissue becomes damaged or inflamed, it can lead to desynchronization of organ clocks and cellular clocks.
Are Organs Secretly ‘Time’ Machines?
Besides the master clock in your brain, the organs in your body have their own clock, the so-called peripheral clocks. These clocks are located, for example, in the liver, heart, kidneys, lungs, and intestines. They are responsible for regulating local processes such as metabolism, hormonal secretion, and immune responses. Peripheral clocks work together with the SCN to ensure that organs are well aligned with each other. For example, without a well-functioning liver clock, metabolism can become disrupted, leading to weight gain and insulin resistance. Another example, a disrupted circadian rhythm (due to, for example, night work or irregular sleep patterns) can disrupt the pancreas clock.
This leads to reduced insulin sensitivity, higher blood sugar levels, and an increased risk of metabolic diseases such as type 2 diabetes. Thus, the wrong light at the wrong time can have a negative impacton blood sugar regulation.
Time also Ticks in the Cell
Besides the master clock and the organ clocks, our body has the cellular clock at a deeper level, where each cell has an internal time mechanism (except red blood cells, embryonic cells, some immune cells, and some cancer cells).
The cellular clock regulates numerous processes that occur in a cell, such as gene expression, DNA repair, energy production, cell repair, hormone production, and immune activation.
For example, DNA repair in skin cellsworks at a higher level in the afternoon than in the morning because the UV index is stronger then. An example of a self-protective mechanism of the body that is under circadian control and also an example of how a time-giver (strength of UV light) influences a regulator (the expression of DNA repair in the cell).
We have already talked about clock genes that essentially ignite the circadian rhythm. The technical terms for these clock genes are CLOCK, BMAL1, PER, CRY, REV-ERB, and RORA. It becomes too complex to go into detail about the functioning of each clock gene, but the most important thing to remember is that each gene has a specific function in the cell, and they influence each other.
For example, CLOCK and BMAL1 ensure that the other clock genes function well, while PER and CRY, for example, start or stop the cycle of certain activities (such as DNA repair). As an example, research showsthat dysregulation of clock genes increases the risk and growth of breast cancer due to circadian disruption caused by chronic night shifts.
CLOCK and BMAL1 promote the growth of cancer cells when they are overactive, while PER2 normally inhibits the growth of cancer cells. Loss of PER2 can accelerate cell growth. CRY1 has an inhibitory effect on breast cancer by disrupting energy production and repairing DNA damage, but when CRY1 is less active, the damage actually increases. CRY2 can also inhibit the cell growth of breast cancer. Disrupting these clock genes through night shifts disrupts the balance and can promote cancer. Yan, Y., Su, L., Huang, S., et al. (2024). Circadian rhythms and breast cancer: unraveling the biological clock’s role in tumor microenvironment and ageing. Front. Immunol., 15, 1444426
We have talked abouttime-givers like light and nutrition andtime regulators (such as clock genes) that initiate processes based on the input from time-givers from central control of the brain, the organs, or within the cell. But in between, there is an important bridging function, and that is where timekeepers come into play.
Timekeepers: eye, skin, intestines, and lungs
Our body has four organs that are in direct contact with the outside world and play a crucial role in the functioning and synchronizing of the biological clock. These are the eyes, the skin, the intestines, and the lungs. Besides their primary functions, they are observers of time.
The Eye: the Central Gateway to the SCN
The eye is a large concentration of receptors. In addition to visual photoreceptors (which convert light information into vision), the eye has non-visual photoreceptors. These do not transmit visual information to the brain but information about light type, light intensity, light spectrum, and light duration. Information that is directly passed on to the SCN, making the eyes the gateway to the central coordination area of the biological clock.
The most important non-visual photoreceptors in the eye are intrinsic photoreceptor ganglion cells (or ipRGCs). These cells contain a pigment called melanopsin, which is particularly sensitive to the light spectrum of blue light, making blue light the greatest impact on the biological clock. Evolutionarily, this also makes sense, as blue light has the most fluctuation throughout the day, making it a very accurate Zeitgeber.
The Skin: the Largest Organ and Detector of Time
Besides the eye, the skin is an important observer to regulate the biological clock. The skin also has photosensitive receptors that detect light and send information to the SCN, such as melanopsin (just like in the eye), but also neuropsin. In addition, skin cells contain circadian clock genes, which help regulate optimal skin function and quality. On the skin itself, there are numerous circadian processes such as sebaceous gland activity (highest in the afternoon), skin temperature (peaks in the afternoon, drops at night), blood flow (highest in the afternoon), and cell renewal (peaks at midnight). The biological clock also influences collagen synthesis and wound healing, whereby wounds heal faster that are sustained during the day.
The sun is the highest quality timekeeper for optimal functioning of the skin as an organ. For example, the morning and evening sun, with a high degree of red and infrared light, stimulates both the production and quality of collagen, which results in strong and firm skin, thereby slowing down skin aging. Under the influence of the biological clock, peroxiredoxin (an antioxidant enzyme) reaches its highest activity in the early evening, suggesting that this is an optimal time for skin repair. Synchronized skin cells repair DNA damage faster and activate antioxidants better, making them more efficient in responding to harmful influences. In contrast, asynchronous skin cells (due to, for example, disturbed sleep) have a reduced defense against oxidative stress, which can lead to accelerated skin aging and damage to collagen and elastin.
The Bacteria in your Gut Sense Time through Food
In addition to the eye and skin, the intestines also play an essential role in perceiving time and regulating the biological clock. The gut microbiome, consisting of trillions of bacteria, has its own circadian rhythms and actively communicates with both the central clock in the SCN and the peripheral clocks in organs and tissues.
In addition to nutrition, light also appears to be an important timekeeper for the gut flora. Exposure to UVB light through the skin increases vitamin D production, which directly influences the composition of the gut microbiome. When the skin absorbs UVB light, vitamin D levels rise and the presence of beneficial bacterial species, such as Lachnospiraceae and Ruminococcus, increases.
This suggests the existence of a skin-gut axis, whereby sunlight via the skin not only influences the biological clock, but also regulates gut health and immunity. The timing of food intake appears to be themost important timekeeper for rhythmic microbiome activities, which underscores the role of the intestines as an observer.
The Lungs: more than a Respiratory Organ
In addition to the eye, skin, and intestines, the lung also plays an important role in perceiving time and regulating the biological clock.
The lung is constantly in contact with the outside world and detects signals such as air quality, temperature, and present microorganisms. Like other organs, the lung contains clock genes that are rhythmically active and influenced by environmental factors such as breathing, stress hormones, and temperature.
In addition, exposure to endotoxins (toxins from bacteria) appears to influence the circadian rhythm of the lung, suggesting that the lung actively anticipates inhaled pathogens. The airway epithelial cells (the protective lining of the airways) in particular play a role in this. Their clock genes respond to signals such as airflow and breathing, which means that the lung not only receives time-dependent signals, but also processes them and possibly forwards them to other bodily processes.
This makes the lung not only a respiratory organ, but also a crucial link in the alignment of the immune system and metabolism at the right time of day. Although more research is needed, it seems plausible that the lung, via signals about air quality and pathogens, contributes to the central coordination of the biological clock.
In Summary
Finally, a brief recap of all of the above.
- We now understand that the biological clock plays a crucial role in our health, influencing hormone regulation, metabolism, sleep quality, and immune function.
- We now know that circadian rhythms are controlled by clock mechanisms in our brain, organs, and cells, which work together to regulate processes at the right time.
- We understand that external timekeepers, such as light, nutrition, and movement, are essential for the synchronization of internal clocks.
- We realize that disruptions in these rhythms, for example due to incorrect timing or irregular exposure to light, can lead to health problems such as metabolic disorders, weakened immune function, overweight, intestinal problems, and more.
- We are now learning that understanding the interaction between timekeepers, regulators, and observers can help us optimize our circadian system for better health.
It is bizarre and fascinating at the same time how the concept of timing has such a profound impact on health. And thus, it is also a key factor in resolving health complaints.
Stay tuned for more and stay in sync!
