Learning to live in harmony with your internal clock is the first step toward a long and healthy life.
Explore Biological ClocksEvery morning, waking with the sunrise, and every night, falling asleep under the cover of darkness, we obey an ancient rhythm that governs all life on Earth.
Complex mechanisms that regulate sleep-wake cycles, metabolism, hormonal balance, and even mood.
The science of biological rhythms that holds the key to solving problems from insomnia to metabolic diseases.
Understanding internal clocks opens amazing possibilities for improving health and quality of life.
The human biological clock is not a single mechanism but a complex hierarchical system. At the top of this system is the suprachiasmatic nucleus (SCN) - a tiny area in the hypothalamus containing about 20,000 neurons that serves as the central clock 4.
The SCN receives information about illumination directly from the retina and synchronizes the work of all peripheral clocks in organs and tissues. These peripheral clocks are found in almost every organ and have some autonomy, although they obey the central regulator 3.
At the molecular level, biological clocks represent an elegant feedback system based on cyclic interdependence of proteins and nucleic acids. The main components of these molecular clocks are CLOCK and BMAL1 proteins, which act as accelerators, activating genes responsible for our daytime activity 1.
They are opposed by REV-ERB-α and REV-ERB-β proteins that function as brakes, as well as Period and Cryptochrome proteins that accumulate in the cell during the day and gradually break down at night 14. This molecular dance creates an approximately 24-hour cycle that determines our circadian rhythms.
| Component | Function | Analogy |
|---|---|---|
| CLOCK and BMAL1 Proteins | Activation of circadian genes | Gas pedal |
| REV-ERB-α and REV-ERB-β Proteins | Suppression of CLOCK and BMAL1 activity | Brake |
| Period and Cryptochrome Proteins | Accumulation and decay during the day | Speed regulator |
| Suprachiasmatic Nucleus (SCN) | Central rhythm coordinator | Orchestra conductor |
Until 2012, it was believed that REV-ERB-α and REV-ERB-β proteins played only a supporting role in the biological clock, making minor adjustments to the main mechanism. However, research conducted by scientists at the Salk Institute led by Ronald M. Evans fundamentally changed this understanding 1.
Researchers developed a unique mouse model in which both REV-ERB genes could be turned off in the liver at any time using tamoxifen. This allowed them to study the function of these proteins in adult, fully formed organisms, avoiding possible complications of embryonic development 1.
Genetically modified mice with floxed REV-ERB-α and REV-ERB-β genes in liver cells were created.
Adult mice were injected with tamoxifen, which triggered the process of turning off both genes in the liver.
Mice with disabled REV-ERB genes showed significant circadian rhythm disturbances.
Scientists discovered that genes controlled by REV-ERB overlap with genes activated by CLOCK and BMAL1.
| Parameter | Normal Mice | Mice with Disabled REV-ERB |
|---|---|---|
| Nighttime Activity | Low | High |
| Daytime Activity | High | Low |
| Blood Fat Levels | Normal | Elevated |
| Blood Sugar Levels | Normal | Elevated |
| Circadian Rhythm Coordination | High | Impaired |
This discovery showed that REV-ERB-α and REV-ERB-β are not secondary players but equal participants in the main clock mechanism. "Now we have an accelerator and a break, each equally important for creating the daily rhythm of the clock," explained Ronald Evans 1.
A direct molecular connection between circadian rhythms and metabolism was established, explaining why people with disrupted daily rhythms (shift workers, frequent time zone travelers) more often suffer from metabolic diseases such as diabetes and obesity 1.
Modern research on biological clocks relies on a variety of tools and methods:
Mice with regulated clock genes allow studying the function of specific genes in mature organisms 1.
An estrogen derivative used to activate or deactivate specific genes at a given time 1.
Visualization of gene activity in real time, for example in experiments with Escherichia coli bacteria 2.
Running wheels for rodents, actigraphy for humans, allowing tracking of activity and rest cycles.
| Reagent/Method | Purpose | Example Usage |
|---|---|---|
| Tamoxifen | Inducible gene knockout | Studying REV-ERB function in adult mice 1 |
| Luminescent Proteins | Gene activity visualization | Creating biological clocks in E. coli 2 |
| Melatonin Assays | Circadian rhythm assessment | Studies in isolated bunkers 4 |
| Body Temperature Monitoring | Indirect circadian rhythm assessment | Research by Czeisler and Kronauer 4 |
Biological clocks are not an invention of mammals or even multicellular organisms. They have existed for billions of years and are found in cyanobacteria, plants, fungi, and animals 3.
Synechococcus elongatus has the simplest clock model consisting of just three proteins: KaiA, KaiB and KaiC.
Amazingly, these proteins continue to demonstrate 24-hour phosphorylation and dephosphorylation cycles in a test tube with ATP without DNA involvement 3.
Rhythms arose to separate DNA replication processes (at night) from its repair (during the day) 3.
The "peroxiredoxin hypothesis" suggests that clocks arose to prepare for the daytime surge of reactive oxygen species formed during photosynthesis 3.
Interestingly, in humans and other mammals, erythrocytes (cells lacking DNA) also have circadian rhythms based on peroxiredoxins - universal proteins that protect cells from oxidative stress 3.
This suggests that circadian timing mechanisms are deeply conserved throughout evolution and operate through multiple interconnected pathways.
The study of biological clocks is a brilliant example of how fundamental scientific research can lead to practical applications in medicine and daily life.
Understanding the subtle mechanisms of biological time regulation opens the way to personalized chronomedicine, where treatment is prescribed taking into account individual circadian rhythms, which can significantly increase therapy effectiveness 14.
Observing circadian rhythm hygiene - regular sleep during dark hours, limiting exposure to bright light in the evening, orderly eating patterns - can become a powerful tool for preventing many diseases, from diabetes to depression.
As research conducted in isolated bunkers has shown, our internal clocks continue to tick even in the absence of external signals, obeying their own rhythm close to 24 hours 4. This is an innate, deeply rooted property of living matter that we are only beginning to understand and which we can learn to manage wisely.