Of owls, larks and alarm clocks: could out-of-sync body clocks be contributing to human disease?

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Date: Mar. 12, 2009
From: Nature(Vol. 458, Issue 7235)
Publisher: Nature Publishing Group
Document Type: Article
Length: 2,529 words

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Ten years ago, researchers reported on three families with an extreme 'lark' problem. Larks are people who naturally wake up early in the morning, and are the opposite of 'owls', who wake up and go to sleep late. But many of the members of these families had particularly acute larkness, waking up on average around 4 a.m. and falling asleep around 7.30 p.m. (1). The researchers later found that the families, who were diagnosed with familial advanced sleep-phase syndrome (FASPS), all carried mutations in a gene called PER2, which is involved in setting the human body clock (2).

By some estimates, more than half of the population in industrialized societies may have circadian rhythms that are out of phase with the daily schedule they keep. Such people are said to have 'social jet lag'--a term coined by Till Roenneberg of Ludwig Maximilians University in Munich, Germany. Some of these are larks, some owls, and some have pretty standard human rhythms that are disrupted by shift work or travel. In modern societies, circadian-rhythm disruptions can arise from simply spending too much time indoors, something that can make such workers decidedly "owlish", Roenneberg says. Even the one-hour time change made by many countries at this time of year can take some adjusting to.

If larks and owls are forced to follow normal schedules, they run into all kinds of problems with disabling insomnia and sleepiness. But disrupted rhythms could have graver consequences than that. In 2007, an expert working group at the World Health Organization's International Agency for Research on Cancer in Lyon, France, concluded that "shift-work that involves circadian disruption is probably carcinogenic to humans" (3), after reviewing the existing evidence. Equally strong conclusions have been drawn from evidence that links circadian-rhythm problems to psychiatric disorders, metabolic syndrome and a range of other illnesses.

Researchers now are working to understand those links. Some suspect that health problems arise from a third kind of jet lag--one that arises when the circadian rhythms in different body tissues lose synchrony with each other. In 2006, the European Commission started funding EUCLOCK, a 16-million [euro] (US$20-million), five-year project involving some 34 researchers whose goal is to understand how the circadian clock synchronizes with cycles in the environment. In particular, the researchers are trying to work out what type of schedules are the healthiest fit for individuals' biological clocks. "People have been researching this for 50 years," says Anna Wirz-Justice at the Centre for Chronobiology in Basel, Switzerland, "but I think the methods are only now coming up to address this properly."

In nearly all organisms, patterns of biochemistry, physiology and behaviour oscillate with the daily cycles of light and dark, often with near-perfect timing. People forced to live in a 28-hour cycle still show fluctuations of almost exactly 24 hours in their core body temperature and levels of the hormones melatonin and cortisol (4). In mammals, many of these cycles are directed by a 'master clock' in the brain's hypothalamus called the suprachiasmatic nucleus (SCN)....

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Gale Document Number: GALE|A196152572