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| Japan Daily Press |
Sometime in the future a person could be waking up after a short 16-hour snooze. Preparing a hearty meal to start their “day”, they will probably be thinking about the hours ahead of them. Maybe they have a night shift, a morning to see friends and family, a hobby to indulge in somewhere in-between. Time is cheap when you don’t have to sleep for another 36 hours.
This of
course is fantasy, but could it eventually become a possibility – or even a necessity? After all, society in
the 21st century is “Open 24/7”. In crude terms of thinking, there
is a need for us to adapt to our new social patterns.
A growing
number of individuals in countries affluent and developing alike are taking on
employment that requires work during hours that are deemed “unsociable”. Late-night
bar workers, early-morning cleaners and night-shift security – most people know at least one or two people
who work in these sectors.
Working
unsociable hours usually comes with better pay and more flexible free time in
the day, but research is starting to uncover the dangerous long-term effects of
an abnormal day/night cycle.
Following a
rough 24-hour period and reacting to simple environmental elements, Circadian
rhythms are our biological cycles that adhere to the light/dark cycle of the
day. In humans they affect sleep cycles, hormone release, body temperature and
many other important physiological factors. Abnormalities in these cycles can
cause insomnia, depression and even obesity.
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| Psychology Blog |
All human
necessities are controlled subconsciously by our biological clocks, named so due to their tendency to cause the
hand of our Circadian cycles to turn. These clocks drive all life, not just
humans, and are genetically rigid in our make-up. Tucked in the hypothalamus part
of the brain is a bundle of neurones called the Suprachiasmatic Nucleus (SCN).
This construction of neurones is accepted to be the human Master Clock, the
conductor of all of the other biological clocks.
Hijacking
our own daily rhythms and biological routines would be a very complex ordeal,
but we are starting to understand more about Circadian Rhythms.
To avoid the
risks of obstructing our natural biological cycles we would need to modify our
own physiology - our needs to rest and sleep (accepting that eating and
drinking is, pretty much, impossible to avoid). Lots of our Circadian rhythms
summate together to produce one large desired effect, which makes the “root” of
each Circadian action hard to locate. Scientists at the University of Oxford
have recently managed to pinpoint a very significant element involved in Drosophila (fruit fly) Circadian
rhythms: a genetic “on-off switch” for sleep. Gero Miesenbock and team used
light to turn on genetically modified cells that react to certain wavelengths,
due to the presence of the gene. The light caused dopamine release, which
inhibited sleep-promoting neurones, thus waking the flies.
Working
directly with Drosophila’s neurones,
Fang Guo at Brandeis University, Massachusetts, demonstrated an opposite effect:
in the same type of fly, after activating neurons in a biological clock,
glutamate is release which then turns off neurones in the part of the Master
Clock that promotes activity.
Although we
already know that dopamine in animals is generally related to active behaviour,
and that glutamate inhibits areas of the SCN in humans, we can’t yet assume the
same model seen in Drosophila as in more complex organisms.
This type of research does, however, demonstrate that we have already started
to pick-apart the inner workings of Circadian activity.
Looking at
something closer to humans, Circadian rhythms in mice have been found to
lengthen when caffeine is involved. We all know that coffee alters our sleep
pattern, but researchers Oike, Kobori, Suzuki & Ishida found in 2011 that
administering caffeine into the growth media of both human bone-cancer cells
and mouse stem cells actually alters the length of the biological cycles. On an
intracellular level it was seen that processes associated with high-level
activity were extended, causing a lengthening shift in the whole “daily” cycle
of the cell. Another experiment with caffeine was attempted which involved the
stimulant being added to ex vivo (outside of organism) liver cells, which
resulted in signal delays in the SCN – something that could be linked with the
lengthening of the cycles.
To try
something with a whole organism, the researchers ran a third test with live
mice. “Limitless” supplies of caffeine were made available to the subjects for
a week under normal light-dark conditions. The findings of this in vivo experiment were that the mice
were indeed active later into their dark periods in comparison to the control
group.
Although for
these mice the administration of a caffeine
fountain was a rudimentary way of modifying circadian rhythms, this study
raises two interesting points: firstly, as conserved as the genetic foundations
of these biorhythms are it is possible to modify them. Secondly, the
modification of these cycles can be performed in complex, mammalian organisms
and not just isolated tissue.
As our
Circadian rhythms are firmly ingrained into our cells’ genetics, the cogitation
of altering something so essential and, some could say, ancestral is a daunting
task. Surely these axial genes that make up our natural rhythms are hard to get
at? Yes, for now, but further specific advances in the field (which if you’re
interested is called Chronobiology) have uncovered a clue to unmasking the “cogs”
of the biological clock:
Scientists
at the Salk Institute (CA) have discovered a tell-tale sign to identify the
strength of someone’s Circadian rhythms. They were looking at the REV-ERBa
structure, which is a particular receptor found on many genes associated with repressing
transcription. The REV-ERBa is considered to be associated with inhibitory
effects in biological clock activity, although the mechanism of its workings
was previously unknown.
What the
team at Salk found surrounding this gene was that 2 proteins work together to
change REV-ERBa concentrations. They expected that this is an important
mechanism used in biological clocks to lower levels of activity during night
time, when an individual is asleep, and then raise levels again in the morning.
The 2 proteins perform different tasks to “turn the hand” around on the
biological clock; the F box protein FBXW7 selects REV-ERBa for degradation in
the morning which causes activity levels to rise, and then Cyclin-dependent
Kinase 1 (CDK1) phosphorylates REV-ERBa (a prominent sign of activation in
biology) when activity levels become too high. What’s more interesting, is that
when CDK1 phosphorylates REV-ERBa it is also signalling to FBXW7. This means
that when REV-ERBa levels are very high (i.e. at night, again) FBXW7 is drawn
to the component to begin the cycle all over again.
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| Zhao et al. (2016) |
The
importance of this study is that it identifies something that has not been seen
before: Circadian rhythm amplitude. The strength of gene activation in these
biological clocks is being controlled by 2 proteins, both dependent on each-other.
If there were drugs that could potentially alter the levels of one, we would be
able to not necessarily control our biological rhythms but at least steer them
in the right direction. For example, If an early-morning shift worker found
that they couldn’t settle-down to sleep early in the evening, they could take a
drug that could induce an earlier CDK1 effect. This would lead to REV-ERBa
levels increasing earlier on in the day, causing sleepiness earlier than normal
and wakefulness earlier the next morning – just in time for a 5am shift.
It is very
important that we understand that our biological rhythms have evolved with us
over millions of years. They are crucial parts of our physiology, and although
the studies explored in this article aim to show that they can be altered it
must be stressed that we are a long way off from the future described in the
first paragraph. For the time being we are as reliant on our natural Circadian rhythms
as much as any other organism, but that doesn’t mean that our increasing
knowledge of genetics can one day give us the controls to our own cycles.
Sources:
- - Piemental, D., Donlea, J.M.,
Talbot, C.B., Song, S.M., Thurston, A.J.F., & Miesenbock, G. (2016).
Operation of a Homeostatic Sleep Switch. Nature, 536 ,
333-337. doi: 10.1038/nature19055.
- - Guo, F., Yi, W., Zhou, M.,
& Guo, A. (2011). Go signalling in mushroom bodies regulates sleep in
Drosophila. Sleep, 34 (3),
273-281. Retrieved from http://www.bio.brandeis.edu/rosbashlab/profile.php?imagename=fang.
- - Oike,
H., Kobori, M., Suzuki, T. & Ishida, N. (2011) Caffeine lengthens circadian
rhythms in mice. Biochem Biophys Res
Commun, 410 (3), 654-658. doi: 10.1016/j.bbrc.2011.06.049
- - Zhao, X., Hirota, T., Han, X.,
Cho, H., Chong, L., Lamia, K. ... Evans, R.M. (2016). Circadian Amplitude
Regulation via FBX27-Targeted REV-ERBa Degredation.Cell, 165 (7), 1644-1657. doi: http://dx.doi.org/10.1016/j.cell.2016.05.012.
a - Psycology Blog image: http://a2levelpsychology.blogspot.co.uk/2015/06/a2-level-circadian-rhythm.html
- Japan Daily Press image: http://japandailypress.com/know-your-body-clock-and-lose-weight-2810428/
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a - Psycology Blog image: http://a2levelpsychology.blogspot.co.uk/2015/06/a2-level-circadian-rhythm.html
- Japan Daily Press image: http://japandailypress.com/know-your-body-clock-and-lose-weight-2810428/
-
- - Salk Institute. "Powering
up the circadian rhythm." ScienceDaily. ScienceDaily, 26 May 2016.
<www.sciencedaily.com/releases/2016/05/160526124908.htm>
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