Steering the Elephant I found myself looking up the definition of the words genome and gene expression because I did not understand how they were being used in an article. The search led me to a very interesting magazine piece that introduced me to cellular clocks called, How The Body’s Trillions Of Clocks Keep Time, by Veronique Greenwood. I know about circadian rhythms, the master clock, and dark-light cycles relating to sleep and wakefulness, but I did not know that cells have their own clocks, and the extent that these clocks are being coordinated by the master clock. It is a very interesting article and can be read at either Wired and/or heard at Quanta Magazine. There is an image of blue-green algae protein that is worth the trip.

It is all about timing

In general, cellular clocks and the master clock do much more than regulate when we wake and sleep. These clocks trigger all kinds of things during the day and night, such as when nail growth starts and stops, or when we eat, or how we combat disease, and so much more. There is an interesting line of research linking circadian rhythms and DNA repair, along with the relationship between circadian clocks and cancer. There is another study researching the administration of chemotherapy later in the day, rather than early in the morning, so that hair loss is minimized.

As Ms. Greenwood points out, except for embryonic stem and cancer cells, the vast number of cells that affect humans are those with clocks. According to Bianconi et al there are 37.2 trillion human body cells. One wonders why an organism with that many cellular clocks does not have clock mash ups.

In a description of the work performed at the Panda Research Lab housed at the Salk Institute, a five step process related to cellular clocks is described which helped me understand why one does not have clock mash ups:

  1. Turn on/turn off cycles – Cells can activate and deactivate. A portion of a cell turns on (the rhythm), beginning a process of converting DNA (transcription) into RNA, which in turn creates proteins (translation) used in the protein activity of that cell. At some other point, that same portion of the cell turns off. One moment your hair grows, the next moment it stops.
  2. Time – There are systematic times throughout a 24 hour period where cells change their function. Daily cellular rhythms are guided by the expression of genes, i.e. genetic instructions — the turning on, turning off cycle.
  3. Autonomy — Cellular clocks can run autonomously, meaning that they do not have to have a master clock to function — A potential for mash ups.
  4. 24 hour cycle — Circadian rhythms are the name for this 24 hour cycle and are controlled by the Master Clock.
  5. Coordination – The master clock (suprachiasmatic nucleus), using a non-visual light sensing process provided by the retina, coordinates the 24 hour cycle for behavior and physiology — Moderating the potential for mash ups.

Starting with #5, Coordination, a non-visual light sensing (photic) process means that there are photo sensitive cells (Retinal Ganglion Cells) in your retina that do not generate images, but are sensitive to wavelengths of light. The optic nerve conveys these sensed wavelengths to the suprachiasmatic nucleus where they are interpreted, and coordinated with cell clocks throughout the body as to what type of light wavelength is being sensed and what to do. Morning light is blue (wake up), evening light is red (get ready for sleep), and darkness is darkness (go to sleep).

Jumping to #3, Autonomy, where the cellular clocks can operate on their own, could create problems if it were not for the master clock coordinating activity. Hence, mash ups are avoided. More than the avoidance of mash ups, the master clock organizes cellular clocks in a way to help the host organism survive efficiently and predictably. The simple recommendation of, “get a good night’s sleep”, takes on a whole new dimension when we consider the role light wavelengths play in the daily cycle of all those cellular clocks. Blue light not only signals that it is time to wake up, a message is sent to those cellular clocks that are supposed to work in the morning to turn on, and for those cellular clocks that work in the dark to turn off. And on the rhythms go, turning on and turning off, throughout the 24 hour cycle.

From a top down perspective, the more we find out about cellular clocks and circadian rhythms, the easier it becomes to understand why it is important to pay attention to things like how we avail ourselves of natural light and sleep cycles. It is one thing to continuously stay up too late surrounded by blue wavelength artificial light, and think we can make up our need for sleep on the weekend, which we do not. It is quite another thing when we realize that pushing our system by undervaluing natural light and the importance of sleep, we are messing around with the mechanism that coordinates 37.2 trillion clocks that need to work together every day.

Mash ups anyone?