Tick, Tock! The Molecular Basis of Biological Clocks

A long time ago, before the rise of humans, before the first single celled organisms, before the planet even accumulated atmospheric oxygen, Earth was already turning, creating a 24-hour day-night cycle. It’s no surprise, then, that most living things reflect this cycle in their behavior. Certain plants close their leaves at night, others bloom exclusively at certain times of day. Roosters cock-a-doodle-doo every morning, and I’m drowsy by 9:00 pm every night. These behaviors roughly align with the daylight cycles, but internally they are governed by a set of highly conserved molecular circadian rhythms.

Jeffrey Hall, Michael Rosbash and Michael Young were awarded the 2017 Nobel Prize in Physiology/Medicine for their discoveries relating to molecular circadian rhythms. The official statement from the Nobel Committee reads, “…this year’s Nobel laureates isolated a gene that controls the normal daily biological rhythm. They showed that this gene encodes a protein that accumulates in the cell during the night, and is then degraded during the day. [They exposed] the mechanism governing the self-sustaining clockwork inside the cell.” What, then, does this self-sustaining clockwork look like? And how does it affect our daily lives (1)?

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Molecular Connections Between Sleep Deprivation and Inflammation

Anyone who has travelled across time zones knows how unpleasant it is when the regular rhythm of your biological clock is disrupted. Jetlag results when the body’s internal clock, or circadian rhythm is out of sync with external cues for “day and “night”, resulting in insomnia, extreme tiredness, difficulty concentrating and various other unpleasant symptoms.

On the bright side, jetlag is at least a temporary misery that is usually over after a few days of acclimation to the new time zone. Long-term disruption of the natural sleep/wake cycle, such as encountered by frequent long-distance travellers, shift workers, or people with physiological conditions that affect circadian rhythms, can be much more debilitating. Longer term health effects that have been associated with constant disruption of circadian rhythms include, insomnia, concentration problems, and increased susceptibility to diseases associated with chronic inflammation such as cancer, diabetes and cardiovascular disease.

Despite the fact that many of the genes and proteins involved in central control of circadian rhythms are known, the reason for the implied association between circadian clock components and immune function is not understood. Recently, a paper was published in the July issue of PNAS that identified a potential link between a circadian clock component and chronic inflammation. Continue reading