Red blood cells and circadian rhythms

Do you wake up every morning right before your alarm clock goes off and ever wonder why? This is due to circadian rhythms. Circadian rhythms are daily cycles (oscillations) of behavior processes that occur throughout the day (~24 hours long), such as sleep/wake cycles and eating. In humans, mutations in genes that control circadian rhythms can lead to disorders such as jet lag, shift work, familial advanced sleep phase syndrome (FASPS), delayed sleep phase syndrome (DSPS), and diabetes. Many researchers have conducted circadian rhythm studies, including myself, to better understand the underlying mechanism of the clock. In humans, the suprachiasmatic nucleus (SCN) is the master pacemaker that controls all oscillators in the peripheral tissues, such as liver, pancreas, lungs, and adipose tissues. These peripheral tissues all have their own ~24 hour rhythms; however, they are all kept in synchrony by the master SCN. In the past circadian rhythms were believed to only be linked to DNA and gene activity. However, on January 27, 2010 research from Universities of Cambridge and Edinburgh was published in Nature showing there are circadian rhythms in red blood cells. The reason why this research is so significant and interesting is that unlike other rhythmic cells, red blood cells do not have DNA.

These researchers developed a unique model system to study circadian rhythms in human red blood cells and a possible future mechanism for studying circadian rhythms in other non-transcriptional cells. In this experiment, the researchers hypothesized that peroxiredoxins oxidation could be used as the rhythmic marker in cells lacking transcriptional abilities (DNA). Peroxiredoxins are a class of antioxidant enzymes that regulate proper peroxide levels in the body. In order for something to be declared a circadian rhythm it must follow three properties, the first property being that a period of a rhythm must persist in the absence of temporal (time) cues with a period of ~24 hours, the term for this is called a free-running rhythm, secondly the period of a rhythm must remain the same over a range of temperatures, and third the circadian clock can be reset by external signals. The researchers tested these properties and did indeed find there are circadian rhythms in red blood cells. The researchers also tested how circadian rhythms could be interconnected to metabolic pathways; they did this by studying the NADH/NADPH levels found in red blood cells under constant conditions (free-running rhythm) and their data supports that there are ~24 hour rhythms. They also found rhythms in ATP indicating that the circadian rhythms found in red blood cells are from metabolic origin.

As a circadian researcher this research on red blood cell rhytmicity is very cool and these results spark interest in future studies to come. This research has laid the foundation for other studies on transcriptional and non-transcriptional cells, which could ultimately lead to a massive expansion of our understanding of circadian rhythms. From these studies we can also obtain a better understanding of cellular metabolism and peroxiredoxins.

“Even a stopped clock is right twice a day” -Marie von Ebner-Eschenbach

Here is the news release about the research, also for the full Nature article you can find it through the Au library site without paying.