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?

Here is what you should know about what this is. Within you there is a systematic way to react to stressors, and most of the time the system works very well. At other times, this systematic process can work against itself which can degrade how you do things. If the systematic way you react to stressors works against itself for long periods of time, there is a very good chance that something on you will break.

The chart above depicts your body’s stress regulation system when reacting to daily stressors, in a very simplified way. The complicated (meaning scientifically dense) way is explained by Megan Gunnar and Karina Quevedo.

So what does the chart describe? It is describing the neurobiological reaction that helps us cope with stress. There are two systems in your body that react to stressors, the SAM, or sometime called SAS (sympathetic- adrenomedullary system), and the HPA (hypothalamic- pituitary-adrenocortical system). They are coordinated with each other by the hypothalamus. The SAM and HPA are on either side of the Blood-brain Barrier, a barrier that protects the brain from harmful things floating in your blood. The SAM is part of the sympathetic nervous system, the part that readies the body for flight or fight, and resides in the lower brain stem and spinal cord. It is on the opposite side of the Blood-brain Barrier from the HPA. The hypothalamus activates adrenal gland secretions along with central nervous system coordination to execute activation of SAM and HPA. SAM reacts to fast, fight/flight types of stressors, where as HPA reacts to more complicated, long term stressors.

Generally, the system can adapt to stressors and balance both physical and psychological needs, quite well. However, during prolonged periods of negative stress, some of the secretions that activated the HPA to enhance the reaction, also deactivate the HPA as a protection. So, if the SAM is still reacting to a stressor and the HPA is deactivating the system’s response to the same stressor, you got a problem. Continuously pushing the system beyond its capacity to adapt to a stressor can do harm to you…in all kinds of ways!

Regulating reactions to stressors is not the only function the hypothalamus is involved in. The hypothalamus plays a central role as the pacemaker for one’s circadian rhythms, which are behavioral and bodily processes that are modulated within a 24 hour time period and repeat every day. Waking and going to sleep, eating and defecating, changes in your heart rate and blood pressure throughout the day, and body temperature increasing in the morning and decreasing in the evening; are some examples of circadian rhythms. These internal rhythms are genetically coded and certain rhythms are affected by day-night light cycles. Disregarding circadian rhythms and day-night light cycles can adversely effect hypothalamic response to stressors.

Putting this into perspective, I started out discussing the neurobiologic system used to respond to any stressor. The good news is that we have a great way to accommodate and adapt to the stressors in our lives. The bad news is that if we ignore the stressors that are taking a toll on us, we are putting ourselves in jeopardy. I also added two other pieces of information that can effect how we react to stressors that are not usually talked about in a discussion about stress reactions – circadian rhythms and day-night light cycles. I have not gone into depth on those two, but will in a future post.

If you are trying to figure out how well you are adapting to the vagaries and grind of daily life, it is important to understand that there are three pillars to your analysis, not one:

1.  You have an internal systematic way to react to stressors and that system can work against itself causing damage,
2. You have a genetically coded set of circadian rhythms and you need to know how to predict them, and
3. Your circadian rhythms are guided by day-night light cycles, both of which can degrade the effectiveness of your SAM-HPA system.

Practically speaking, if you are an early riser, like to work hard all day long, take few breaks, don’t drink much water, eat at odd times, and stay up late at night — you are playing with fire.