Anyone got any info on ncor1?

iv'e gone through many pages upon pages but i can't find anything else on ncor1 other then anything about the mice with the gene edit. i was wondering if anyone on here has any information on this gene and its interactions within human's? because if it acts in the same way as in the mice without any real genetic side effect or problems it could be a good alternative to the mstn type of 'edit'.
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  • there's plenty of data about it online. Although I have no idea what you mean. What do you think it's supposed ti do? Edit genes for you? or make you live longer or what? cause i'm not seeing anything that indicates it's useful for either. it's part of a repressor protein that condenses particular bit of chromosomes so they cna't be transcribed, effectively down regulating a few enzymes. 
  • Looks like there would be some side effects.


    Let me know if you need this translated into not science speak.
  • edited October 2015
    i probably should've added more info when asking my question but i was kind of in a hurry last night - essentially tweaking the ncor1 gene in mice to not be active (as shown during knockout mice test's) allows those mices muscles to grow more effectivly and is quite similair to the mstn (myostatin) gene in the way that it is an inhibitor for muscle growth however instead of resulting in hypertrophy like mstn it results in denser muscle tissue and more mitochondria in those muscle cells allowing for the muscles to be twice as effective (it does result in some hypertrophy but as it is not a growth inhibitor in the way of size like mstn it rather makes the muscles in mice stronger). the mice with the gene inhibited also seemed to grow muscle more readily without stimulation (aka exercise)
    and back to my question i was wondering about weather or not this gene interacted with the same or similar pathways in the human body to allow for the same effect? and with us being human would there be any negative effects known with this gene interacting with anything other then what it does in the mice, no negative effects have been noted in mice 

  • So, this is kind of a difficult question, in as much as there hasn't been any work done on this thing with humans. One thing we do know is that it's important for both thyroid regulation and for building retinoic acid receptor proteins (omg does it always have to come back to vitamin A?). The retinoic acid thing makes me wonder...
    However, it's unclear for a cursory reading if its up or down regulating these processes.
    There's a note that is forms repressive chromatin structures. This is a flag in my brain for cancery goodness in as much it's kind of used in growth and development and while we like growing and developing, these things unchecked cause issues. 
    It seems to interact with at least 20 other proteins  (no big surprise there)  many of which are fairly important.

    It seems to show some evidence of working in a similar fashion to what you are referencing in said mouse study. Would you mind dropping a link? I'll read up on it more, but the short answer atm is that it's involved in a lot of stuff. While inhibition or knock outs may be positive in the short term, there are just a crap ton of things it's involved in. 
  • A word of caution: the articles you posted are from a news outlet and a press release, which as a rule make discoveries sound a lot cooler and more far-reaching than the actual science published. There is (always) an amplification of the significance and application as successive outlets hear about a new discovery. Whenever possible, try to trace down the primary article (the paper actually written by the scientists who made the discovery) and read what they say. Take all else you hear with a grain of salt.
  • Looks like they did muscle specific targeting. This is an important piece of info. This way, they were didnt mess with the other functions. They also mention that NCoR1 knockout mice tend to die if you don't do this targeting.

    They basically modded normally terminal NCoR1 knockout mice back to functionality is all areas except their muscles. The process sounds like a real pain in the ass.  This was necessary tho, to make sure that there targeting was precise. On the other hand, targeting such a hack in an adult might be a lot easier.
    Worth a bit more reading...
  • i believe this is the original article although i don't really have time at the moment to read through it i will read it asp,

    what do you mean by it being easier to do this hack in an adult? is it because an adults cells are easier to target?

  • Well, since you are affecting the areas post growth, you don't need to work with knitting together the knock out area. On the other hand, there is no evidence from this paper) that this will work in mature models. Downregulation usually works well, but for all we know, this could basically be a turn the brakes on early or not at all situation. 
  • hmm true.. do you think it would work in premature models then if not developed adults? because if so this would still be extremely useful for people with muscular dysthrophy if found at a young age that is. is there any known way to test this in an adult human model without you know using a live human? i feel this research could be useful for quite a few people and was wondering how one would go about running a test for such things to see if this procedure would work
     
  • Just so you know, when @glims says "mature models" he means it in the developmental-biology sense, which (for humans) means the time before they are born, and much much earlier depending on what specifically is involved here. 
  • ohh i see now that makes a bit more sense actually since he did mention post growth and well turning it on early or not at all, just didn't realise he meant that early 

  • Does the muscle gained from repressing NCOR1 have to maintained in order to keep that amount of muscle mass, or is it a permanent effect?
  • it's not permenant it seems but it is far easier to gain and maintain it 

  • This sucks if you want mass. It looks like this is converting fast twitch fibers into slow twitch fibers if I'm reading this right. So increased mass in calf muscles and other slow twitch dominant areas makes sense.
  • edited February 2016
    yes it may suck for building mass but if your wanting speed and strength not endurance then this is the way to go, also if you were able to change the way your body processess energy, eg, through PEPCK-C you could effectively be very strong and very fast for short periods of time (short being maybe half an hour of sport or so) 
  • You might have that backwards. This is building highly aerobic slow twitch endurance fibers. Power and speed are fast twitch fibers (3 types of fast twitch) and tend to have very few mitochondria, relying on creatine phosphate for energy instead. The fast twitch fiber are bigger and should give you bulk.

    Slow twitch are to batteries as fast twitch are to capacitors.

    Anyway, the rodents bulked a little bit in the leg muscles, but I don't think it improved their bench press.
  • So, is there something out there that builds fast-twitch fibers?

    Also, what about muscle tone? Will these new fibers need strengthening, or will they increase your strength just by being there?
  • I was wrong on the number of varieties of fast twitch fibers. There are 2 primary ones in humans, but it looks like more varieties exist. I was also wrong on on my interpretation of the paper. Apparently type IIa fibers are rich in mitochondria (which I didn't know). These are fast twitch muscles, but kind of built for medium loads & longer use than the more powerful IIb fibers. I guess they are like supercapacitors.

    So the animals developed more of these and type I fibers and saw a reduction in IIb (I maybe falsely assumed it was turning IIb into Ia-my bad).

    @TheGreyKnight: this is a very in depth topic. There are so many things that determine the actual strength of a muscle as well as the amount you can get. We should add something about this in the Wiki, but here are some factors:
    1. Actual tensile strength of the fibers (tension is vital)
    2. neuro engagement
    3. Fiber types
    4. sarcomere width
    5. etc

    So there are genes that address various aspects of these types of things. That myostatin knockout is pretty awesome though.

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