Body Clocks: What They Are and How They Work

Lately, with the new year, the #TimesUp movement, awaiting Disney’s movie A Wrinkle in Time based on one of my favorite childhood book series, and just watching my children grow faster than I thought possible, I have been thinking a lot about time. The continuous march forward, the constant rotation of the planet, and the revolution of the Earth around a distant star in its determined path all have far-reaching effects on our physiology and behavior. Our biological clocks affect everything from our sleep-wake cycles to our fertility to our mental and physical health. And it’s not just us that have them: Every living thing on Earth, including bacteria, protists, fungi, plants and animals, has them. But what do they do and how do they work?

A sleepy ferret minds his biological rhythms. Photo by Kimberly Tamkun at Wikimedia Commons.

Generally speaking, a biological clock is an organism’s inborn way of regulating its functions with respect to time. Many of these biological clocks follow circadian rhythms (changes that follow a 24-hour cycle). Vast portions of our planet have been exposed to dramatic but mostly predictable environmental changes on a 24-hour cycle since long before life existed, so it makes sense that us lifeforms have developed a means to make the best of those changes: sleeping when food is less available, having higher metabolisms when we are active, being more alert during times we are most likely to be interacting with the world.

Diagram of a human circadian rhythm by YassineMrabet at Wikimedia Commons.

Melatonin is a hormone widely known to synchronize circadian rhythms in vertebrates (animals with backbones) to the light-dark cycle of the day and night (or to an indoor room with a light timer). Melatonin is produced in response to darkness, and the longer the night, the more melatonin is produced. Rising and falling melatonin levels help determine sleep-wake cycles in animals. In animals that breed seasonally, the changing peaks of melatonin levels that correspond with dark nights getting longer or shorter stimulate the reproductive system to help synchronize breeding physiology and behavior with the seasons. Although we have known about melatonin and its effects for nearly a hundred years, we are now learning that it seems that all organisms, including bacteria, protists, fungi, plants and animals, make it. Whether it has the same effect in all organisms is yet to be determined.

In vertebrates, melatonin is produced by the pineal gland, a small structure in the center of the brain. In birds, reptiles, amphibians and fish, the pineal gland has light-sensitive cells that receive light as it passes directly through the skull and the brain! In mammals, the pineal gland receives a light signal through a more complicated pathway: Light is detected by light sensitive cells in the retinas of the eyes. They send this signal to the suprachiasmatic nucleus (SCN) in the brain, which relays it to other brain areas and then to the pineal gland. The SCN in mammals is commonly called “the master clock” due to its important role in synchronizing body rhythms with light cues.

Diagram of the human brain and the SCN by the
National Institute of General Medical Sciences at Wikimedia Commons.

Body rhythms are determined at the cellular level through the interaction of a small number of genes called clock genes. Clock genes have been found in every animal, plant and fungus studied so far. Originally, it was thought that in mammals, clock genes would only be found in the SCN. However, it now looks like clock genes are active in all cells and the SCN functions more like an orchestra conductor synchronizing the rhythms of the organs throughout the body.

Many clock genes have been discovered, and they all seem to work based on similar processes. Just last year, scientists Jeffrey Hall, Michael Rosbash, and Michael Young, were awarded the 2017 Nobel Prize in medicine for their research on clock genes in fruitflies. They found that biological clocks are self-regulated within the cell: Morning sunlight turns on a gene called the PERIOD gene, which starts to produce a protein called the Period protein. As long as there is light, Period protein accumulates to higher and higher levels. Another protein, named Timeless, shuttles Period proteins into the nucleus, where the DNA lives. The Period proteins shut down the activity of the PERIOD gene, while a third protein, called Doubletime, regulates the destruction of the excess Period proteins. The result of this process is that by nightfall, Period proteins have disappeared and sunlight is needed to start the cycle anew. This work by Hall, Rosbash and Young inspired a whole new field of molecular biology of circadian rhythms.

We have a lot more to learn about biological clocks and circadian rhythms, but what we do know is that their effects are wide-ranging. Whacky circadian rhythms have been implicated in sleep disorders, depression, bipolar disorder, cancer, obesity, and diabetes. And what else will we learn about them? Only time will tell.