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Scientists find mechanism to reset body clock

Discussion in 'Other Health News and Research' started by Ecoclimber, Mar 20, 2014.

  1. Ecoclimber

    Ecoclimber Leaving for awhile

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    Date: March 20, 2014
    Source: University of Manchester
    Summary:
    Researchers have discovered a new mechanism that governs how body clocks react to changes in the environment. The discovery could provide a solution for alleviating the detrimental effects of chronic shift work and jet-lag.

    Scientists find mechanism to reset body clock

    Researchers from The University of Manchester have discovered a new mechanism that governs how body clocks react to changes in the environment.

    And the discovery, which is being published in Current Biology, could provide a solution for alleviating the detrimental effects of chronic shift work and jet-lag.

    The team's findings reveal that the enzyme casein kinase 1epsilon (CK1epsilon) controls how easily the body's clockwork can be adjusted or reset by environmental cues such as light and temperature.

    Internal biological timers (circadian clocks) are found in almost every species on the planet. In mammals including humans, circadian clocks are found in most cells and tissues of the body, and orchestrate daily rhythms in our physiology, including our sleep/wake patterns and metabolism.

    Dr David Bechtold, who led The University of Manchester's research team, said: "At the heart of these clocks are a complex set of molecules whose interaction provides robust and precise 24 hour timing. Importantly, our clocks are kept in synchrony with the environment by being responsive to light and dark information."

    This work, funded by the Biotechnology and Biological Sciences Research Council, was undertaken by a team from The University of Manchester in collaboration with scientists from Pfizer led by Dr Travis Wager.

    The research identifies a new mechanism through which our clocks respond to these light inputs. During the study, mice lacking CK1epsilon, a component of the clock, were able to shift to a new light-dark environment (much like the experience in shift work or long-haul air travel) much faster than normal.

    The research team went on to show that drugs that inhibit CK1epsilon were able to speed up shift responses of normal mice, and critically, that faster adaption to the new environment minimised metabolic disturbances caused by the time shift.

    Dr Bechtold said: "We already know that modern society poses many challenges to our health and wellbeing -- things that are viewed as commonplace, such as shift-work, sleep deprivation, and jet lag disrupt our body's clocks. It is now becoming clear that clock disruption is increasing the incidence and severity of diseases including obesity and diabetes.

    "We are not genetically pre-disposed to quickly adapt to shift-work or long-haul flights, and as so our bodies' clocks are built to resist such rapid changes. Unfortunately, we must deal with these issues today, and there is very clear evidence that disruption of our body clocks has real and negative consequences for our health."

    He continues: "As this work progresses in clinical terms, we may be able to enhance the clock's ability to deal with shift work, and importantly understand how maladaptation of the clock contributes to diseases such as diabetes and chronic inflammation."



    Story Source:

    The above story is based on materials provided by University of Manchester. Note: Materials may be edited for content and length.

    Journal Reference:
    1. Violetta Pilorz, Peter S. Cunningham, Anthony Jackson, Alexander C. West, Travis T. Wager, Andrew S.I. Loudon, David A. Bechtold. A Novel Mechanism Controlling Resetting Speed of the Circadian Clock to Environmental Stimuli. Current Biology, 2014 DOI: 10.1016/j.cub.2014.02.027
    ______________________________________________________________________
    This is interesting as well:

    Daily rhythms of our genes are disrupted when sleep times shift
    A new study from the University of Surrey, published today in the journal PNAS (Proceedings of the National Academy of Sciences), found that the daily rhythms of our genes are disrupted when sleep times shift.

    Researchers placed twenty-two participants on a 28-hour day in a controlled environment without a natural light-dark cycle. As a result, their sleep-wake cycle was delayed by four hours each day, until sleep occurred 12 hours out of sync with their brain clock and in the middle of what would have been their normal 'daytime'. The team then collected blood samples to measure the participants' rhythms of gene expression.

    During this disruption of sleep timing, there was a six-fold reduction in the number of genes that displayed a circadian rhythm (a rhythm with an approximately 24 hour period). This included many regulators associated with transcription and translation, indicating widespread disruption to many biological processes.

    The study also revealed which genes may be regulated by sleep-wake cycles and which are regulated by central body clocks. This finding provides new clues about sleep's function as separate from the circadian clock.

    Senior author Professor Derk-Jan Dijk, from the Sleep Research Centre at the University of Surrey said: "This research may help us to understand the negative health outcomes associated with shift work, jet lag and other conditions in which the rhythms of our genes are disrupted.

    "The results also imply that sleep-wake schedules can be used to influence rhythmicity in many biological processes, which may be very relevant for conditions in which our body clocks are altered, such as in ageing."

    Co-author, Dr Simon Archer, from the School of Biosciences and Medicine at the University of Surrey, added: "Over 97% of rhythmic genes become out of sync with mistimed sleep and this really explains why we feel so bad during jet lag, or if we have to work irregular shifts."

    Story Source:

    The above story is based on materials provided by University of Surrey. Note: Materials may be edited for content and length.

    Journal Reference:

    1. Simon N. Archer, Emma E. Laing, Carla S. Möller-Levet, Daan R. van der Veen, Giselda Bucca, Alpar S. Lazar, Nayantara Santhi, Ana Slak, Renata Kabiljo, Malcolm von Schantz, Colin P. Smith, and Derk-Jan Dijk. Mistimed sleep disrupts circadian regulation of the human transcriptome. Proceedings of the National Academy of Sciences, January 2014 DOI: 10.1073/pnas.1316335111
    Full Article Access in PNAS located here:
    Mistimed sleep disrupts circadian regulation of the human transcriptome
     
    Last edited: Mar 21, 2014
  2. Calathea

    Calathea Darkness therapy

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    Well, I was on a 25 hour cycle until I started messing around with light therapy and later darkness therapy, which fixed it nicely. Surely if you know that it's about melatonin and light exposure, specifically light around 465nm (blue), this should be the first thing you're playing with?
     
  3. Martial

    Martial Senior Member

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    So basically scientists have found our reset switch? Wow Science what will you amaze me with next! :D
     
  4. alex3619

    alex3619 Senior Member

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    Melatonin and light are two of about fifteen things known to affect this. Many of us do not respond to either.
     
  5. Martial

    Martial Senior Member

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    If a person has an underlying infection this can cause sleep changes that won't change until its cleared out, whether bacterial, viral, or parasitic...

    I know for M.E. it is a case of highly inflamed cytokines. I wonder if the inflammatory immune response it produces needs to be brought down before people see benefit in those cases..

    One other thing I was curious about though I think is the completely wrong way to handle it.. If M.E. is a exaggerated immune response and some suspect an auto immune nature has anyone ever benefited from taking steroids or immuno suppressive drugs to control symptoms with benefit?

    I have no doubt it is very improper treatment but just curious if this has ever been done, obviously another issue is constantly re activated viral components so again seems like a stupid idea but still curious about if its been done previously.
     
  6. alex3619

    alex3619 Senior Member

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    Cortico-steroids used to be a standard treatment for CFS, going back decades now. It typically only suppresses symptoms. I am not sure it ever led to sustained improvement, but I have not gone back and read the old research.

    PS Such approaches broadly suppress the immune system. It must be remembered that in ME we have both an under- and over-active immune system. Cortisol etc. suppresses most of the immune system. It doesn't differentiate. Its like trying to get flattened steak by driving a steamroller through a butcher shop, then only buying the nice flattened pieces.

    Rituximab is much more selective, though definitely more severe. It attacks B cells. If Tregs are involved, then we need to look very closely at what subtypes, what the regulating factors are, and how to affect them.

    It was discovered a year or two back that oxidative stress in the hypothalamus alone is enough to disrupt circadian regulation. Hands up who has an oxidative stress disorder?

    A slightly low cortisol level is worth boosting at low doses though, but that was not what was discussed here.
     
    Last edited: Mar 21, 2014
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  7. Martial

    Martial Senior Member

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    Interesting stuff, yeah I know steroids would be a terrible idea in the long run but just was curious if it was ever done, there are many things people can take non pharmaceutic-ally to reduce the various different immune response inflammation pathways in the body though, obviously the most important thing is to work on reducing these cytokines in a way that does not supress activity but turns back on normal regulation of cell and immune activity.

    Dr Buhner discusses many different types of herbs that achieve this function. Though the function is on the treatment of lyme disease and co infections like Mycoplasma the function is the same. Reduce cascading inflammatory cytokines in different pathways while treating invading pathogens, treat immune system regulation, oxidative support, and proper nutrients and minerals to prevent wasting.

    Methylation would be another huge benefit he does not cover but a lot of good info on natural products to reduce different response pathways and it is very specific to each selection, using individualized herbs to target different inflammatory processes simultaneously.

    Recently they found out the issues with chronic Lyme infection and why it can be so challenging is the bacteria reliance on mangenese for growth and survival, this is completely out of the norm of all other bacteria so the normal bodily response of shutting down iron production to starve bacteria does not work. They are now working on a process in which to stop the enzyme production of mangenese from the spirochetes to starve them off and this would work as an effective cure to the infection.

    I just wonder what the underlying process for the true cases of M.E. are not the ones that get misdiagnosed. I know there are a lot of different theories in place but in my opinion there has to be some underlying susceptibility with a combination of an environmental effect. Some kind of toxin that drove this excessive cytokine response in the first place. Unless it is strictly an auto immune illness of the immune system itself; causing weird kinds of exaggerated activities with no immediate apparent cause. Even auto immune diseases have been found to be sourced to certain stimuli in the system, subsequently finding ways to stop the response to cure it. It just seems with M.E. that it effects the entire system without any specific selected source such as arthritis effecting joints, celiac effecting gluten, M.S. targeting the CNS, etc.

    Dr. Shoe Maker describes this process pretty well. So damn... I kind of just really wonder what the hell is going on to drive the immune system haywire in the first place and give people a real definitive cure for it.
     
  8. Ecoclimber

    Ecoclimber Leaving for awhile

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    It is important reminder not to forget the role of the glutamate receptor, ionotropic, kinase 2 (GRIK2) and neuronal PAS domain protein 2 (NPAS2), genes involved in glutametergic neurotransmission and circadian rhythm regulation, respectively, as to be consistently associated with CFS in independent genomic analyses. These previously unrecognized associations should provide exciting new hypotheses in the study of CFS.
     
  9. alex3619

    alex3619 Senior Member

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    Glutamate toxicity is one of the fifteen or so factors I looked at years ago that can drive circadian changes.
     
    SickOfSickness likes this.
  10. Ecoclimber

    Ecoclimber Leaving for awhile

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    They found a biomarker for ME/CFS for it would not be commercially feasible involving Delta Wave sleep distubrance in ME/CFS using EEG technology.
     

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