By DRS. DAVID NIESEL and NORBERT HERZOG
Have you ever felt that after-lunch slump, when you become sleepy in the afternoon? Or an extra boost of energy when it’s time to go home later? This is actually natural for humans and occurs for very specific reasons. There are two control mechanisms, called sleep/wake homeostasis and a circadian biological clock that humans and other mammals use to regulate times we are awake and when we need to sleep. These systems work together to control sleep and define our wake periods.
Mammals have a natural periodicity of 24 hours, our so-called biological clock, which is driven by something called circadian rhythm, which helps us determine when we should be awake or asleep each day. An adult human’s highest sleep potential generally occurs from 2 a.m. to 4 a.m. There is a second high potential for sleep from 1 p.m. to 3 p.m. Doesn’t this help explain why some cultures have an afternoon siesta? Sleepiness during these circadian periods will be less if we have had sufficient sleep and more intense when we do not sleep well. This circadian rhythm also works to our advantage during the day, making us feel more alert.
Our biological clock can be affected by a variety of environmental cues, such as bright light and heat, which can alter or entrain your biological clock. Through a process called temperature compensation, humans and other mammals are able to maintain a normal day over a range of temperatures. Among these environmental stimuli, light is arguably the most important. We are beginning to discover more about how exactly light affects the biological clock. This could provide new avenues to control sleep disorders and also address problems with jet lag in our increasingly mobile society.
Recent studies have addressed how we might be able to reset our biological clocks in the absence of light. Exposure to light causes certain proteins in the brain to undergo chemical changes. One study investigated a protein called Eukaryotic Initiation Factor 4E, or EIF4E, that helps our cells produce new proteins such as period proteins, which are key to sleep regulation.
For EIF4E to function, a small molecule called phosphate must be attached to it through a process called phosphorylation. A key experiment showed that if researchers mutated the EIF4E protein in a mouse’s brain so it could not attach to phosphate, the mouse was not able to reset its biological clock in response to light. Therefore, controlling the phosphorylation of EIF4E could be a way to reset our biological clocks.
Sounds easy, right? If we could just find a way to alter the phosphorylation of EIF4E, we could cure insomnia and perhaps moderate jet lag. The issue is that EIF4E helps cells make proteins all over the body, not just in the brain. Any potential drugs would have to work exclusively in the hypothalamus, a region of the brain that helps regulate sleep and other processes.
It is important to understand the mechanisms that control our biological clock, as disruptions can lead to health disorders and serious diseases like cancer, diabetes and heart disease. However, much more work is needed to safely manipulate the biochemical network of our circadian rhythm.