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Uncoupling light uncouples your knowledge: Ubiquitination 6 is live

Discussion in 'Mitochondrial Rx' started by Jack Kruse, Mar 5, 2015.

  1. Jack Kruse

    Jack Kruse Administrator

  2. Penny

    Penny New Member

    Holy God! Thank-you Thank-you Thank-you for spelling all this out so that someone like me could actually know what to do when - truly, I was so lost between the protein, the mTOR, the sirt1/2, AMPK, ketogenic diet - to exercise or not and if so when and when to eat - this blog was awesome - didn't quite fathom #5 - but 1-4 really spoke to me - especially the elevation/suicide bit...
    BTA likes this.
  3. Josh

    Josh New Member

  4. yewwei.tan

    yewwei.tan Gold

    Quick clarification @Jack Kruse , the reference to the "Nocturnal Exercise Rx" did not come with a hyperlink to a separate page.

    This is my interpretation, do correct me if I'm wrong. (and consider adding it to the blog so that people don't end up confused ;))

    The Leptin Prescription basically says: (http://jackkruse.com/my-leptin-prescription/)

    If you have trouble falling asleep I suggest 3-5 minutes of body weight exercises right before bed (pushups or air squats are fine, but avoid this if your evening cortisol is high).​

    That's simple enough to understand, since exercise in general will:

    - increase AMPk activity, and thus increase fat oxidation and ketosis => high FFA oxidation rates help cool down the brain during sleep (ketosis and cold was explained in the blog)
    - blunts insulin levels => low insulin means melatonin goes up
    - increased serotonin conversion from the gut => more melatonin
    - endorphin receptor stimulation => always good. See ItsTheWoo's blog post -- http://itsthewooo.blogspot.com/2015/02/the-mu-endorphin-receptor-weight.html

    Night time exercise WILL NOT WORK if exercise cannot activate AMPk well. The way you tell this for sure is with a high evening cortisol. If you are feeling shitty and can't sleep after exercise, it's probably a good sign that you should back off the night time workout protocol.

  5. Jack Kruse

    Jack Kruse Administrator

    focus on the prize I just gave you......not what you want
    Josh likes this.
  6. yewwei.tan

    yewwei.tan Gold

    Quick excerpts -- http://tanyewwei.com/notes/jk-ubiquination-6

    Need some time to think, but coming soon are some musings about practical considerations regarding exercise and protein consumption, how to monitor response to exercise and protein consumption to get good outcomes, and perhaps an expansion of a private email that I wrote regarding mTOR- and Sirtuin-affecting compounds like resveratrol and curcumin.
    David Limacher and NeilBB like this.
  7. kovita

    kovita Gold

    great notes, Yew. You are so efficient and fast! There is a lot to think about in my personal context. We have been talking previously about autophagy signaling in pregnancy, remember? I can observe a lot of changes in myself since in every trimester. With the previous pregnancies I never noticed a think, maybe I just never thpught about myself and what I "feel like". Few examples of things something inside of me instructed me to do as I moved to the third trimester:

    can skip lunch on many days (absolutely impossible in 1. and 2.t)
    started to use intranasal red light during the CT and most of the days feelong like CT in the morning and (this is new) in the evening just after the sunset
    cannot push myself to do any HIIT anymore, much more attracted to yoga, stretching and long walks
    my sleep is further improving, I even need on avergae about 30 min less than during the last year
    one more thing...as my whole family went through influenza lately, I have mot contracted acute disease. Instead I developed with some delay exactly the same "sickness" as when I lately took antibiotics (think about my lyme). I would swear something was killing them, the comment about virus as potential activator of immunity in cancer stole my eyes. I was suspecting whey protein but now I have maybe better principle.

    I still have some doubts about IF in women. I definitely reached very high fertility (conception at first "accident" ;-) longterm ketotic, but not IF. The break between dinner and breakfast was only 13-14 hours. Maybe there are different rules for how IF looks like in women and men. I am becoming very confident just by observation, than females are absolutely not biochemical/physiological copies of males, and that it goes even farther and it turns out there should be apllied biology for males and applied biology for females.
  8. Jack Kruse

    Jack Kruse Administrator

    Of course their are differences........I already explained to you all why. EE 7. Women pre menopausal are designed with less myelin to be more sensitive to environmental EMF. This is how epigenetics are sensed and how they are transmitted is in UBi 5. When women stop bleeding they become myelinated and less sensitive to environmental EMF. The same relationship exists in kids and why they should not use technology until they are 25. Myelin protects.......as does the sea within and around you. When you are more sensitive to the environment, you are by definition more LR than someone who is not........therefore women are built by design this way.......how does a women use IF to her advantage to offset he lack of myelination. CT in water........THIS SERIES IS BRINGING MANY CONCEPTS TOGETHER

    Time for you to do the same.
    Last edited: Mar 8, 2015
    David Limacher likes this.
  9. Jack Kruse

    Jack Kruse Administrator

    Leptin Resistance (LR) is a synonym for an up-regulated ubiquination rate.
    David Limacher and Josh like this.
  10. Again maybe my role to ask the 'stupid' question...........ubiquination in a real 'generalized' way of speaking is not 'good' it is very energy demanding breaking down, recycling and synthesizing new proteins is a very energy intensive business. It is however of course absolutely necessary to life (there is so much to read recently so I need to 'study' more - but in the example of the octopus is it breaking down proteins and re-constituting them to achieve the effects it wants?)

    It is also 'up-regulated' (increased) by the modern world specifically nnEMF. You also say here is it synonymous with leptin resistance (not good). But and this is one of the things I want to get clear it is 'down-regulated' (decreased) in a lot of the diseases of 'older people' I am thinking specifically of T2D, cancer and Alzheimer's. In T2D there is then an inability to recycle mitochondria, in AZ the inability to break down mis-folded proteins etc. In that way I suppose it is analogous to 'free radicals' etc which are neither 'bad' or 'good' they have a vital function in the body, excessive amounts are 'bad' but the inability to create them is also a huge problem. And I suppose a problem the high fat low carb people make worse with their prescriptions.

    This in a sense though then is not some 'clear' message some clear 'to do' message..................it goes back to a more old fashioned message nothing in excess is 'good' the balance is what is important, everything has it's place and it is not good to get un-balanced or excessive in what we do. Not a 'revolutionary' message but useful I suppose, like avoid nn EMF, don't get carried away by the promise of 'anti-oxidants' be always aware of the environment you are in. Now I have to get back and study that octopus some more..............
  11. NeilBB

    NeilBB New Member

    I don't think its stupid, Pat...I think you are right about it being a balance. But I don't think this is about some kind of "golden-mean moderation"--I think its about "signalling and labeling accuracy"... Here are some of my musings:

    It seems to me it has to be a lot more complicated in reality than just up-regulating or down-regulating "ubiquitination," as an across-the-board whole. The other crucial variable would seem to have to be the specificity in which proteins to degrade and replace and which to leave alone. Precise geographic specificity would seem to be the whole point here... If one were replacing proteins which should actually have been maintained for long term structural support, this would clearly be a problem due to the unnecessary wear and tear and poor use of cellular and metabolic resources. On-the-other-hand, if one were not replacing certain damaged or shorter-term proteins due to mislabeling (poor signalling/inflammation) or lack of amino acid building components (protein deficient diets), then the problem there would be the accumulation of misfolded dysfunctional proteins. Properly functioning cellular signalling and DNA instructions should be able sort all of this out theoretically, but maybe it doesn't do that so well in an altered field. So maybe its not only a matter of the quantity of ubitiquination and autophagy, but also of its quality and specificity.

    Here's an analogy to clarify the point: Lets say that you are a contractor with a large building to maintain. Parts of it are gonna need rennovation, pretty much all the time, right? So, you are given a certain budget and a certain amount of building materials and a wrecking/maintenance crew. Now, if you don't know which floors/wings of the building need to be rennovated at a given time, your wrecking crew may end up tearing down and rebuilding perfectly good areas and pissing away the resources that should instead be used on the old rotting hallway 2 floors down. If the guy that prioritizes the construction projects (lets call him "the ubquitinator") is a drunken idiot, then your building is gonna be in a hell of a lot of trouble, pretty quickly, even if you have a large budget and plenty of building materials. The quantity of material turnover done in a period of time might actually have even been exactly correct , but the work may have been carried out in unnecessary locations because this wrecking crew (lets call them the "microwave gang") may have destroyed a perfectly nice area and usurped resources that were actually intended for another older location.

    In this analogy, upregulating ubiquitination would simply mean that the drunken "ubiquitinator" hired a larger wrecking crew. It would say nothing about providing that wrecking crew with the accurate directions on where to tear the walls down. And without that precise direction (cellular signalling), there would be no hope of maintaining the building no matter what the raw materials taken in. And we would arrive squarely back at the idea that food (raw material) doesn't matter unless signalling is fully functional.
  12. Jack Kruse

    Jack Kruse Administrator

  13. angie-s

    angie-s New Member

    I am very confused now. Ubiquitination 6 is telling me that if I eat a protein rich diet (which is required by the Leptin RX), I will upregulate the mTOR pathway and thus stop autophagy. But I need autophagy to rebuild me defective cells and reverse disease. So does that mean I should not eat ketogenic diet if I want to reverse my disease? No doubt this is my misunderstanding but I would be grateful if someone could explain. I want to become leptin sensitive and reverse T2D.
    I have noticed that after first 10 weeks of leptin reset protocol (I am now in week 26) my improvement has stalled eventhough I am following everything diligently (diet, CT, no nnEMF etc) so it must be the mTor effect.
  14. yewwei.tan

    yewwei.tan Gold

    I think you're doing great kovita :)

    Fasting is never a mandatory thing, and what you're doing with breakfast and dinner sounds like a great plan as is.


    We need to clarify the lack of myelination that women have, specifically with respect to Pregnancy.

    First, readers should note that there is a huge increase in Estrogen and Progesterone during pregnancy way above any possible normal physiological level. This continues to increase all the way from conception until birth.

    We're talking 5-8 times the normal value of both hormones.


    To me, this means that women get more and more sensitive to environmental effects (including native-EMF and non-native-EMF), while constantly being in a pro-growth stimulatory environment.

    It's important to note that Progesterone is an mTOR inhibitor, while also being a T-cell stimulator. One such study -- http://www.ncbi.nlm.nih.gov/pubmed/22740122

    High progesterone levels stimulating good T-cell function could explain why you're not getting viral infections during your pregnancy.

    Sidenote: if I were the creator of the Universe, I would "want the body to get infected by a virus" during a time when there isn't a good free radical signal :p (like in winter time)​

    High Estradiol (E2) levels on skeletal muscle will promote both AMPk and Akt1 activity, just like Intermittent Fasting would.

    ie: I think that during pregnancy, you don't need to do intermittent fasting or HIIT exercise to get the benefits they normally bring. I think this applies to women as a whole (since they have higher E2), and they don't need to fast as much, or exercise as much, or eat as much protein.

    Cold Thermogenesis activates a whole bunch of other pathways as well, so that is always an option that is beneficial.

    Some mice studies, but they should be relevant enough for making conclusions on the effect of E2 on AMPk and Akt1 in skeletal tissue (increasing both enzymes):

    - http://www.sciencedirect.com/science/article/pii/S0006291X09004410
    - http://onlinelibrary.wiley.com/doi/10.1038/oby.2008.50/full

    Another mice study -- http://www.sciencedirect.com/science/article/pii/S155041311400179X

    But it shows that E2 in the brain (specifically the hypothalamus):
    - increases body-wide Brown Adipose Tissue genesis
    - increases mobilisation of White Adipose Tissue (great for use as stem cells for the baby)
    - decreases hypothalamic AMPk (not to be confused with skeletal tissue AMPk, which is likely increased)​

    The effects of progesterone on mTOR and the downstream pathways, along with the effects of E2, make for a nice mix of growth and inhibitory stimuli, while providing a lot of building blocks (especially from WAT) to make a good baby.

    Sidenote: epithelial cancers are very rare in pregnancy, likely because the above described hormone environment involves a lot of apoptotic stimulus, which prevents cancer despite lots of growth stimulus and lots of ubiquination.​

    However, I still think that women get more and more sensitive to environmental nn-EMF stressors all through pregnancy. This means that needing to control the environment becomes more and more critical. So I think that should be the focus of our attention, instead of doing stuff like Intermittent Fasting. Following an intuitive approach like kovita does with regards to diet and exercise is probably the right thing to do, assuming that the environment is being controlled well enough.

    If you can't control your environment during pregnancy? :confused: That's tough, and at the moment I can't see a way around it except to sleep in a tub of water and remain as ketotic as possible.

    By definition, you're supposed to get more sensitive to the environment during pregnancy, and I don't see a real solution except for actually controlling your environment.

    There must always be a balance between building (synthesis), recycling (autophagy), and destroying (apoptosis).

    The case in Pregnancy as described above is the extreme, whereby you push as much growth stimulus as possible, while also slamming on the brakes with an autophagy or apoptotic stimulus the moment things go wrong.

    You need a lot of energy to make that strategy work, which is why it probably isn't the norm.

    Now that we've got the theory laid down, I am interested in how to achieve that balance in practice. I still need to think about that :rolleyes:

    kovita and Inger like this.
  15. Lahelada

    Lahelada New Member

    Angie, it does mentjon that the leptin reset asks for protein AM but not so much pm and that there is a reason for that. In other words we are talking about behaviour as it should be after you are leptin resistent. Ketosis then = winter diet. Person with persistent inflammation anytime diet. Ketosis as a permanent diet is a resounding NoNo.
    Brent Patrick likes this.
  16. yewwei.tan

    yewwei.tan Gold

    Random commentary to clarify terminology :p

    When we say "ketosis is not a permanent diet", we're talking about true Nutritional Ketosis a la Jimmy Moore or ItsTheWooo. Super low carb, low to moderate protein, high fat => chronic low free radical stimulus.

    We're not talking about a @Danco3636 style diet, which is high-fat, low-carb, but occasionally high protein, and with decent bouts of exercise -- http://forum.jackkruse.com/index.php?threads/reverse-electron-flow.12744/page-2#post-155572

    His diet, with the bouts of high protein and good exercise, allows for free radical signalling despite low carb intake, and can likely be performed chronically.

    Inger, Christos and Josh like this.
  17. BTA

    BTA New Member

    good point - so the BAB is bad ? :confused:
  18. BTA

    BTA New Member

    MTHFR snp - effects serotonin.... over methylation or under is bad news
  19. Thanks Neil, that's quite helpful.
  20. angie-s

    angie-s New Member

    So I still eat BAB but should I eat carbs for dinner or should I eat high fat, moderate proteins and some carbs to get the most balance and for autophagy to work or is there another answer?

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