How does my body clock keep track of time?
Picture the scene: you wake up in the dim light of the morning, and wonder if it’s already time to get up. Just as you reach for your bedside clock, your morning alarm goes off. It’s a handy – if mysterious – skill. But how does the body keep track of time, even when it’s asleep? “When we talk about our ‘body clock’, what we are referring to is our endogenous molecular clock that can be found in practically every cell in our body,” explains Greco, an assistant professor at Humanitas University in Italy. “What this means is that at the molecular level, there are cell mechanisms that bind to specific genes, activate various repressors or inhibit the activity of activators. And all this happens on a 24-hour cycle.” In other words, our molecular clock generates a 24-hour rhythm that affects things such as gene expression, metabolism, and protein levels. And the ebb and flow of these influences when we feel hungry, when we feel energetic and when we feel tired. And if this clock starts to malfunction, the effects can be deadly. This so-called circadian rhythm is 24 hours because – you’ve guessed it – this is the length of a day on Earth. All light-sensing creatures on the planet have some kind of internal clock. Light is the principal signal that resets our central clocks – without this corrective mechanism, your body clock would gradually move out of sync with the world, giving you permanent jetlag. The evolutionary reason for this internal clock was to ensure that our bodily functions could adapt to changes in the environment – most notably between night and day.
Getting mixed signals
However, light is not the only signal. Other factors – most notably food – can also influence our internal clocks. This can cause problems for certain people, such as long-term shift workers. “If shift workers are working and eating during the night – when you are not supposed to eat – this can lead to a de-synchronisation within the body,” says Greco. “Your central clock will synchronise to light, while your peripheral clock will synchronise to when you eat. This can lead to metabolic diseases.” This was a key area of focus in her MetEpiClock project, undertaken with the support of the Marie Skłodowska-Curie Actions programme. Greco was interested in better understanding the connection between circadian rhythms and metabolic pathways. “In particular, we wanted to examine a certain metabolic pathway that regulates methionine,” she notes. “This is an essential amino acid that has many important functions.” Including, Greco says, regulating our body clocks.
What drives our circadian rhythms
Greco was able to confirm that the interaction of this protein with another metabolic enzyme generates 24-hour circadian rhythms. Inhibiting the enzyme disrupted the circadian rhythm. Achieving a better understanding of how such interactions drive our circadian rhythms could one day help us to address metabolic-related conditions, including cardiovascular disease and diabetes. This remains a central motivating factor for Greco. “I now have my own lab, which is looking at circadian disruptions in heart failure. The mechanisms behind this remain unclear, so we are studying how circadian rhythms are changed in failing hearts, and changed in other tissues as well.” A timely reminder to always seek a good night’s sleep – even if it means hitting the snooze button in the morning. Click here to find out more about Greco’s research: Metabolic regulation of the circadian clock
Keywords
MetEpiClock, circadian, endogenous, molecular, metabolic, diseases, genes