Watches play a very important role in our body. We have more than just a biological clock. In addition to the one that ages with us, the so-called circadian clock in our brain keeps our body in rhythm. It controls when we wake up, eat and sleep.
But that is not all. It also affects the finer aspects of our bodies, affecting hundreds of molecular clocks in our cells and organs. There are clocks that regulate metabolism, for example, and others that control how genes form proteins. So it’s not surprising that disruptions to our circadian rhythm – caused by jet lag or shift work, for example – can have devastating effects on our health.
Now scientists are working to tailor treatments to our circadian rhythms. Drugs are being researched in the laboratory that specifically target these control mechanisms themselves. Looking further into the future, will we one day be able to hack our circadian clocks to improve our health?
How the circadian clocks tick
Circadian clocks do not tick forward as much as “classic” clocks do, but rather go through cycles over a 24-hour period. They are essentially clusters of genes and proteins working together. For example, some genes can make proteins during the day. When enough of these proteins are made, they prevent the genes from making more during the night. When levels of these proteins are too low, the genes turn on again in the morning. And so the cycle continues.
These cycles are controlled internally by what is called a “master clock” in the brain’s hypothalamus. It is assumed that this clock synchronizes all other clocks. While it sets its own rhythm, it is also affected by the amount of light that shines in our eyes, when we eat and sleep, and other aspects of our behavior. The three US scientists Jeffrey C. Hall, Michael Rosbash and Michael W. Young received the Nobel Prize in Physiology and Medicine in 2017 for their research into precisely these molecular and genetic mechanisms that underlie the circadian rhythm.
Over the course of research, it has been found that molecular clocks influence many biological functions. A study in mice found that that 43 percent of the animals’ genes follow some kind of circadian rhythm. Most genes appear to produce more proteins during the “rush hours” just before dawn and dusk.
It is difficult to do the same research in humans. But we do know that many human genes work in a similar way. Our hormones and immune cells appear to have circadian patterns that fluctuate throughout the day.
Bacteria Occurrence by Rhythm
Our microbiome also seems to change over the course of a day. When scientists analyzed stool samples from volunteers, they found that some types of gut bacteria are more common during the day, while others are more common at night. The relative frequency of For example, Bacteroidetes bacteria — which can break down starch and fiber in the gut — was 6 percent higher at night. What this means for our health is not yet clear. But interestingly, these patterns seem to be disrupted in people with obesity and type 2 diabetes.
Both of these diseases are more common among people who work night shifts and are at increased risk of cardiovascular disease and cancer. Again, it’s difficult to pinpoint exactly to what extent this risk is due to a disrupted circadian rhythm. But research suggests that working at night can shift the time at which some genes make proteins. Some of these are proteins that are important to the immune system — particularly those that help kill cancer cells.
Based on these early findings, it is not surprising that agents that restore our circadian rhythm are being sought. Some people swear by melatonin or light therapy. Others rely more on altering the timing of meals and sleep to influence their own rhythm. But research is looking for drugs that can act directly on our molecular clocks.
Damage from shift work to health
For example, there is KL001. This active ingredient acts on a protein called CRY. “Clock genes” can turn on the production of CRY, and high levels of the protein can turn it off.
KL001 keeps levels of the CRY protein high, which can affect the length of the circadian period. This can affect genes in the liver that also run according to a circadian rhythm. Even the production of glucose in the liver cells can depend on At least that’s what tests on cells in the laboratory have shown. So, theoretically, a drug with such an active ingredient could help limit the negative effects of shift work on metabolic health and potentially reduce the risk of diabetes.
However, the use of such drugs in humans is still a long way off. Still, it’s an intriguing idea that merits further investigation. Some researchers are already suggesting that we might be able to determine the best time to administer drugs or to perform surgery if we can determine a person’s circadian rhythm more precisely at the molecular level beforehand.
While humans have roughly a 24-hour cycle, there are variations. This is how people can be assigned to certain chronotypes: Are you more of a morning person or an evening person, more of a lark or an owl? And while we wait for the use of drugs that target our body clocks, we can tailor existing treatments based on people’s unique circadian rhythms.
However, simple rules and habits often help to bring a disturbed circadian rhythm back into sync: sticking to regular bed times, getting enough sleep, avoiding artificial light at night.
(jle)
