Following the suggestions of and
concerning smaller articles (approximately 1000 words), I like to try it with a topic I came across last week. It’s about the connection between circadian rhythm (sleep) and mitochondria (energy).
Fig.1 The doomed lonely mitochondrion and the curse of modern communication. Background is from Pixabay, mitochondrion with a smartphone is made by Chapper.
The circadian rhythm
Probably everyone knows that sleep is of huge importance but many people are not aware of the fact that even the time when you go to bed is decisive.
I don't want to go too far into detail but it is a matter of fact that the best time for sleep is the night!
The reason for this dictatorship within your body is the circadian rhythm. In fact, this field of research was pretty controversial for hundreds of years(!) [1,2]. And even today it took until the year 2017 that the Nobel Prize was awarded for this topic. Take into account that sleep is probably one of the most important mechanisms in your life. With this notion, you can estimate how difficult it was to figure out how your inner clock functions.
Important for the circadian rhythm is light and specialized neurons in the so-called SCN [3]. SCN stands for the Suprachiasmatic nucleus and is a tiny region located in the hypothalamus. The neurons of the SCN (by the way the smallest neurons in your brain) are tiny clocks which are getting adjusted by light every day. The first interesting fact is, that the light-detecting cells are not the usual cones and rod cells. Neurons in the SCN are being activated by specialized ganglia cells acting as photoreceptors which even work in blind mice [3].
Light controls a machinery of genes, most important period (PER), timeless (TIM), clock (CLK), cycle (CYC) as well as doubletime (DBT) and cry (CRY) [1,3]. Note: Cursive words in lower cases are the genes, abbreviations in upper cases are the corresponding gene products or proteins. The "clockwork" is as follows (Fig.2):
- Light enters the eye and activates the genes cry and doubletime
- Cry and doubletime producing the proteins CRY and DBT
- CRY and DBT forcing the rapid degradation of the proteins PER and TIM
- Further, PER and TIM are acting together for repressing their own production when the concentration is high enough
- The concentration of PER and TIM elevates again throughout the day (not enough proteins left for suppression!), while the amount of CRY and DBT decreases
- Elevation in the amount of PER and TIM is supported by CLK and CYC
- But CLK and CYC are, in turn, inhibited by PER and TIM
- The highest concentration of PER and TIM is at night (CRY and DBT are not present and the concentration of PER and TIM was not high enough for suppressing their own production)
- Nevertheless, late at night, the concentration of PER and TIM is so high that they start to inhibit their own production again
- The next sunrise will again lead to a rapid decline in the concentration of PER and TIM
Fig.2 Simple illustration of the circadian rhythm. A complex interplay of various genes and proteins regulates the activity of neurons within the SCN (Suprachiasmatic nucleus). Once light enters the eye the protein CRY (and others) are produced and reducing the amount of the proteins PER and TIM. The neurons of the SCN are active now, a new day begins. Within the day the concentration of CRY and others decreases and the amount PER and TIM increases again. In the night PER and TIM achieving their maximum concentration (supported by CLK and CYC) and starting to inhibiting their own production. The next sunlight leads to the next severe drop in the concentration of PER and TIM because of fresh produced CRY. Made by Chapper – unrestricted use allowed.
You see that there is a complex interplay of feedback cycles controlling your circadian rhythm. This cycles can still be carried out even if the SCN is removed from the brain and plated within Petri dishes [3].
In the end, the genes period and timeless are the basis of the circadian rhythm!
Sunlight just prevents that the gene products of period and timeless stay too long which suppresses the activity of the neurons within the SCN.
Therefore, light is solely important for not losing the correct interval (24 hours!).
Once the neurons in the SCN are activated they spread their signals across other brain areas and these areas, in turn, adjusting the clock in the remaining body parts.
These mechanisms are controlling all the biochemical reactions from head to toe.
The paper of Weinrich et al. 2019 [4]
We have already discussed that the mitochondria are producing up to 90% of the energy you need, about 100 kg ATP in total per day (check out my articles here, here and here for more). Therefore, it is of interest whether the circadian rhythm has an influence on the mitochondrial function. Intriguingly, in the last week of September, an interesting paper was published I want to share with you. What makes this paper so special is that the authors used flies (Drosophila melanogaster) and investigated the mitochondrial function within the entire(!) body throughout the day. By doing this they found that respiration (=mitochondrial activity, see Fig.3A) is at highest in the middle of the day. Nevertheless, the amount of ATP lowers throughout the day. At night the mitochondrial function is low and glycolysis peaks. You probably remember that glycolysis is quite inefficient which means your body won't have the capacity for high performance at night (see Fig.3A). What was interesting is that by using light (670 nm wavelength) you can elevate the respiration of the flies even at night. This, however, has tremendous consequences for the natural circadian rhythm.
Fig.3 Illustration of important facts found in the article of Weinrich et al. 2019 [4]. A. Illustration of glycolysis and mitochondrial respiration. B. Respiration of flies within the day. The maximum respiration you can find in the afternoon. Respiration decreases at night but can be interrupted by light. C. ATP content within the body decreases throughout the day. That means ATP is faster consumed than produced. Therefore, the observed respiration in B is no contradiction to this observation. D. While the ATP content declines, the level of glycolysis increases. Nevertheless, this is not sufficient to keep the amount of ATP as seen in C upright. Exact data and details you can find here. Made by Chapper – unrestricted use allowed.
You have to keep in mind that the night is necessary for the regeneration of your body and especially your brain [3]. From the observation of Weinrich et al. 2019 [4] you can estimate that your body is not ready for action at night. With time this may have horrible consequences. Now it's scientifically proven (at least in flies).
Summary
What we can learn here is that working at night or being on parties all the time harms your circadian rhythm and might exhaust your bioenergetic equilibrium. Further, you have to take into account that poor or less sleep accelerates aging (read my article about telomers here, here and here). Do yourself a favor and make sleep to one of the most important moments in your life (at night!!!). This is truly a role sleep deserves. Relax and sleep well! Good night!
Sleeping Mitochondrion - Made by Chapper - Unrestricted use allowed
Regards,
Chapper
Note
This week an article about the purpose of sleep to forget things you experienced has been posted by
References
[1] V. Greenwood, Chronobiologie: Die Uhren in uns, Spektrum der Wissenschaft 2/19.
[2] J. Osterkamp, Nobelpreis für Physiologie und Medizin: Wie unsere innere Uhr tickt, Spektrum der Wissenschaft 12/17.
[3] M.F. Bear, B.W. Connors, M.A. Paradiso, Neurowissenschaften: Ein grundlegendes Lehrbuch für Biologie, Medizin und Psychologie, 3rd ed., Springer Spektrum, Berlin, 2012.
[4] T.W. Weinrich, J.H. Kam, B.T. Ferrara, E.P. Thompson, J. Mitrofanis, G. Jeffery, A day in the life of mitochondria reveals shifting workloads, Sci. Rep. 9 (2019) 13898. https://doi.org/10.1038/s41598-019-48383-y.
Posted from my blog with SteemPress : http://worldofchapper.de/rp295320-ovh/index.php/2019/10/05/sleep-for-your-life-the-reason-why-light-in-the-night-kills-your-energy/