"Sleep too little, or at the wrong time, and the effect is devastating"leif harboe

Here’s something to think about as Easter Term (Oh, inescapable fate!) draws nigh: it might not be worth losing sleep over exam revision. Wait, don’t stop reading yet! We already know that sleep is important for brain function – a high-profile 2013 Science paper showed that the brain uses this time to take out its metabolic trash – but we are now starting to find that it also affects practically every other cell in the body. Sleep too little, or at the wrong time, and the effect is devastating.

This is because our bodies normally keep to a built-in schedule, or circadian rhythm. The rhythm is set by biological timekeepers working together with environmental signals like daylight to tell us when to sleep and eat – though sadly not when to study. Crucial to circadian rhythms are molecular clocks, master regulators of gene activity that act as on/off switches. Levels of clock proteins rise and fall in a 24-hour cycle, as does the activity of the genes they control. Molecular clocks are found all over the body; they are also essential for proper function of the body’s master pacemaker, a group of neurons in a brain region called the hypothalamus.

It thus makes sense that altered sleeping patterns can disrupt circadian rhythms, and by extension our health. Sleep disturbances correlate with mental illness, and the World Health Organisation lists shift work, also characterised by mistimed sleep, as a probable cause of cancer. (Arguing that overdue assignments and PhDs in neuroscience also count is, however, taking things a bit too far.) Understanding precisely how mistimed sleep does this has been difficult, but there is now at least one study linking disturbed sleep and altered patterns of gene activity.

In 2014, Simon Archer and colleagues published a PNAS paper looking at the effect of mistimed sleep on the human genome. To do this, they had their volunteer subjects undergo first a natural 24-hour sleep/wake cycle, then a 28-hour-long ‘laboratory jet lag’ cycle. The volunteers’ jet-lagged sleeping habits were completely out of time with their central pacemakers, meaning that their biological clock was telling them to sleep when they were awake, and vice versa. The researchers then collected blood samples during each cycle and compared their content of messenger RNA (mRNA) molecules. (The production of a gene-specific mRNA is the first step in the information flow from a particular gene to the biological process it controls, and is one indication that the gene is switched on.)

The researchers found that during the normal cycle, levels of several mRNA molecules fluctuated in a regular 24-hour cycle. Thus, when sleep and biological clocks were in time, the genes corresponding to these mRNAs also had circadian patterns of activity. Some ‘rhythmic’ genes controlled the synthesis of molecular clock proteins – as expected – while others were involved in immune defence and responses to stress… which is perhaps something to consider if you routinely catch Exam Term flu!

During the jet lag cycle, however, many of these genes completely lost their rhythm, including most molecular clock genes identified in the ‘normal’ condition. They instead remained at the same level of activity, independently of both the sleep/wake cycle and the central circadian pacemaker. This implies that mistimed sleep alters the normal rhythms of not only molecular clocks, but also the myriads of other biological processes they control.

The take-home message from this is that mistimed sleep makes all sorts of molecular clocks lose their normal rhythm, effectively producing a genetic cacophony. Unfortunately, we still don’t know how long the genome – let alone the brain – takes to recover after an all-nighter. Until we do, it’s worth treating sleep as another essential nutrient, to be enjoyed in the right amount and at the right time. Just like caffeine.