Livin
#43
500 mg of immediate release niacin works great to suppress ldl and triglyceride lipid abnormalities induced by rapamycin. Also raises HDL which keeps the ratio of TG to HDL low indicating that niacin is great for inhibiting metabolic syndrome and nafld. Totally fixes my lipid markers so I’m sticking with it.
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If I don’t want to be obese, I have to eat a reasonable amount of food. I have a lot easier time fasting than controlling portions.
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Do you have a link to that study 
Curious to read about it.
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It’s here on the site. I originally got it from Agingdoc1. Unfortunately you’ll have to search for it. Maybe we need a paper repository?
I think taking rapamycin just before or during a fast is the worst time to take it because when you already have low mTOR because you are fasting, the rapamycin isn’t likely to lower it much more. It will be of much better use to take rapamycin during times when you have high mTOR like the day after a fast. I think then it will have a bigger impact. I have no direct evidence of this of course.
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I really like the approach you are lifting up. Probably we don’t need to stack more things on each other. It’s better to spread them out and that way prolong the effect instead of peaking but as you say this is just guess work. I feel that when I start with my extended fasts again I will try this approach out
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I tend to see the copies of mTOR in different cells having a probability profile of how lowered/inhibited they are and that rapamycin will shift that profile to the extent of being more inhibited. Hence if you take Rapamycin when mTOR is already less active the chances of getting autophagy are higher and you will get more off it on an aggregate basis.
There is an interesting question as to what happens when you are entirely in a fed state and mTOR should be activated, but you take rapamycin. Not all of the copies in any one cell are likely to be inhibited. I am not sure what ic50 is for Rapamycin on mTOR.
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Hence if you take Rapamycin when mTOR is already less active the chances of getting autophagy are higher and you will get more off it on an aggregate basis.
I see where you’re going here but I think you’re looking at this in a little too black and white manner. Autophagy isn’t either on or off. So technically rapamycin isn’t really increasing your chances of getting autophagy but rather increasing the degree of autophagy. Autophagy is always somewhat on, just more when fasting and when mTOR is lower. Here is an analogy for why I think rapamycin is most useful when mTOR is otherwise high. Think of using a cholesterol lowering drug to prevent atherosclerosis. If you take the drug during periods when your cholesterol is already very low, it will reduce cholesterol further, but will have a smaller effect on your risk of atherosclerosis, being that atherosclerosis will already be slowed down by your low cholesterol before adding the statin on top. In that case it’s like fixing what isn’t broke. If on the other hand you take a statin during periods when your cholesterol is elevated, then the statin will have a greater effect, with he reduction in cholesterol being greater and the reduction in atherosclerosis. I see rapamycin as similar.
Another reason why I think rapamycin is of less use when fasting than when eating is because I recall seeing studies where rapamycin did not reduce mTOR further when it was already reduced quite a bit like during fasting. This makes sense given that rapamycin doesn’t fully inhibit mTOR (as a side not that is a part of the reason even extremely high doses are not really toxic).
As to what happens when you’re entirely in a fed state and you take rapamycin. I would think mTOR would not be inhibited as much as if you were fasting, but the degree of inhibition relative to what it would be without rapamycin would be higher than if you took it when you’re not in a fed state. I think the benefits of rapamycin would somewhat correlate with the relative inhibition of mTOR.
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If we look particularly at the mitochondria which is particularly our target for autophagy. Whilst accepting the point that all of these are processes driven in part by probability AIUI the difficulty is the level of autophagy is too low and inefficient mitochondria are not targeted for recycling. What we need every so often is to have a clearout of these.
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An important question that we don’t know the answer to is what is more important, maximizing the degree of mTOR inhibition or the duration. Taking rapamycin dose during the fasting periods will tend to maximize the degree while taking it while eating will tend to maximize the overall duration of mTOR inhibition. What is more important and beneficial is hard to say and depends on a lot of unknown factors.
I think we can say that the problem is that certain mitochondria are not being cleared out as the cells are getting more inefficienct. The question is how to deal with this. Clearly a process needs initiating. Mitophagy is a process measured in hours. (rather than minutes or days) Hence I would think a period of 4-5 hours should be sufficient.
Impaired lysosomal acidification with aging appears to be one of the problems that causes impaired mitophagy. The aging lysosome: An essential catalyst for late-onset neurodegenerative diseases - PubMed
My view is that there is a problem producing the larger proteins as people get older. That will cause a range of difficulties. BECN1 (one of the key autophagy genes) which produces Beclin 1 is long.
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Here is a list of the best unique recorded ITP interventions for males sorted by max lifespan effect. My takeaway from this is that there seems to be something interesting if you are a male mouse to combine the mTOR inhibitor Rapamycin with some sort of glucose regulator such as Acarbose, 17-a-estradiol, Metformin or Canagliflozin.
It would be very interesting if ITP could test to combine Rapamycin (14.7 ppm) with 17-a-estradiol (14 ppm) and start the treatment at 10 months of age. My guess is that it will lead to the best recorded ITP result for male lifespan extension.
Next week I will create the female edition of this list.
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Please make the male and female images the same size, so I can easily put them together side by side ! 
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Here is the female edition
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So Resveratrol actually increases lifespan, minimally, and not statistically significant?
The odd one out in there is “Protandim”, an over the counter supplement, a combination, I believe, of Milk Thistle, Ashwagandha, Baca, Green Tea Extract and Curcumin. Green Tea Extract and Curcumin didn’t increase lifespan on separate ITP trials, so could one (or more) of the other three do the job?
I believe it’s either Milk Thistle or Ashwagandha which is producing those effects.
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