About Time: Inside the science of sleep and circadian rhythms

With three chronobiologists receiving the 2017 Nobel Prize in Physiology or Medicine, the biological rhythm field finally gets is time in the sun.

Chronobiology is a small field. Having been embedded in it for most of my professional
life, I can confidently say that chronobiology has never been a particularly glitzy area, or one that attracts a lot of research funding or media attention. Imagine my delight then, when I woke on October 2 to the news that three chronobiologists, Jeffrey C. Hall, Michael Rosbash and Michael W. Young, had won the 2017 Nobel Prize in Physiology or Medicine.

To wildly simplify things, chronobiology is the wing of biology concerned with cyclical patterns of physiology or behaviour in living organisms. Chronobiology is kind of like the rhythm section of a band: it’s not glamorous, but without it there would be chaos. In the case of humans, chronobiology relates to the biological rhythms that regulate all kinds of things.

These include ultradian (a rhythm whose duration is <24-hour day), infradian (a rhythm >24-hours) and circadian (Latin, meaning ‘about a day’) rhythms. Hall, Rosbash and Young’s work, and the focus of the majority of chronobiology research, addresses the circadian rhythm.

Human circadian rhythms regulate functions like mood, digestion, cognitive performance, and cardiac, respiratory, and renal function. Probably most importantly, circadian rhythms influence sleep-wake timing by regulating core body temperature and the release of hormones responsible for sleepiness.

In 1984, Hall, Rosbash and Young discovered the gene that regulates the internal clock and maintains circadian rhythms in fruit flies. This gene, known as the period gene, produces a protein called ‘PER’, which accumulates during the night, and then breaks down during the day. Their discovery helped other researchers identify the period gene in mammals which, as the Nobel Prize committee said, has helped to explain “how plants, animals and humans adapt their biological rhythm so that it is synchronised with the Earth’s revolutions”.

Studies of the human circadian pacemaker have since shown that the majority of people have a circadian rhythm that runs slightly shorter or longer than the 24-hour day. Short periods (<24-hours) tend to lead to ‘larks’, or ‘morning’ people, and long periods (>24-hours) lead to ‘owls’, or evening people. Despite the natural tendency towards slightly shorter or longer circadian periods, most people are entrained to a 24h rhythm by the light-dark cycle. Because of Hall, Rosbash and Young’s discovery, researchers have been able to pinpoint the area of the brain where PER is expressed; the suprachiasmatic nucleus (the SCN). The SCN is linked to the retina, which is how it learns the light-dark rhythm. It’s also linked to the pineal gland, which releases melatonin — the ‘sleepy’ hormone. Light received in the SCN via the retina suppresses melatonin, making sleep less likely.

If you’ve ever been given advice on how to get a better night’s sleep, this is why you have probably been told to avoid bright light in the evenings; it can make it more difficult to fall asleep. Patterns of light and dark also help to explain difficulties associated with jet lag and shift work, for example. Your internal clock is synchronised to a certain light-dark cycle, when you travel across time zones or change from day to night shift, you change your light-dark cycle.

This adjustment can be difficult and slow — the body takes time to learn the new patterns of light and dark and adjust the clock accordingly. In recent years, research has shown
that repeated exposure to this kind of ‘circadian misalignment’ via shift work can lead to obesity, cardiovascular, gastrointestinal and metabolic disease. In fact, shift work is now defined by the World Health Organisation (WHO) as a ‘probable carcinogen’. Not great news for the millions of shift workers worldwide.

The impact of Hall, Rosbash and Young’s work continues to be felt, and makes them worthy recipients of an honour as prestigious as the Nobel Prize. In a field where research funding is scarce, one can only hope that this win draws attention to the incredible potential of biological clocks to influence human health and behaviour and that increased interest in funding chronobiological research follows.

In the meantime, we can console ourselves in the knowledge that even newly-minted Nobel Prize winner Dr Jeffrey Hall struggled to obtain funding during his years in research, and only nine years ago was quoted bemoaning the fact that his grant applications “have had their lungs ripped out, often accompanied by sneering, personal denunciations — perhaps reflecting the fact that this old-timer has lost his touch”. Sounds like those grant reviewers could have done with a good nap.

Dr Jessica L Paterson, Senior Research Fellow, CQUniversity, Appleton Institute

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