I get the numbers for males in your second post “female edition” ,(above in this thread). “Best ITP longevity interventions”.
The numbers for males in the nr 2 and 3 and 5 interventions from bottom in “Female edition”.
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Ok, I thought you got the data from some other place.
Your questions on low dose in young mice and higher in older reminds me of something dr Alan Green said in this timestamp.
One very interesting ITP study on rapamycin would be to try Alan Green’s approach on mice so that the dose is not the same all the time and instead is increased the older the animal gets. This would be a super interesting ITP study to do.
I think aging starts earlier, some aspects post birth. However, I would tend to agree that starting Rapamycin is probably best in the 30-40 range, but I would suggest a more infrequent cycle to start. (say every 6 months combined with a fast).
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This is why I always combine intermittent fasting with rapamycin, to hopefully sidestep the issue of elevated glucose and perhaps to contribute to additional autophagy. Is anyone else making a practice of fasting during rapamycin exposure?
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What type of intermittent fasting do you practice and how many days do you practice it after you have taken Rapamycin?
This reminds of a thing that Mikhail Blagosklonny wrote and it’s point b which is quite interesting part.
Hyperfunction theory predicts that rapamycin can slow down aging by two complementary mechanisms:
a) directly suppressing the quasi-program of aging
b) reprogramming aging by slowing the developmental-growth program
To demonstrate reprogramming, rapamycin should be given for a brief period during development.
I tend to see aging as mainly driven by two things
a) the feedback system of senescent cells holding back transcription and differentiation (long genes)
b) a reduction in efficiency of mitochondria resulting is less acetyl CoA and ATP which mainly causes problems with translation (also long genes), but also causes transcription problems.
Rapamycin helps here by increasing autophagy which reduces the problem b)
There are other problems such as DNA damage, but those are minor in comparison.
Hence I don’t agree with the hyperfunction theory and although you could describe the above as being programmed I would not personally wish to as it is I think slightly misleading to do so.
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I think Rapamycin helps with a) as well. It prevents senescent cells from forming.
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When started late in life (20-month-old male mice), a low dose (14 ppm) shows better results than a high dose (42 ppm). 20 % vs 11 %i ncrease in median lifespan.
These data are confusing and, at first sight, counterintuitive. If translated into humans, then a low dose should be an optimal intervention for older people. I would really like to hear qualified researchers thoughts about this. Finding answers to contradictory ideas/observations is what brings our knowledge forward.
Is high dose rapamycin giving rise to too much autophagy in older male humans?
How much mTOR activation do aging humans need?
And yes, mice are not equal to men. But mice give us clues to solve scientific questions.
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Ah, now I understand how you mean and I looked at the data again. Super interesting, that the low dose had a better effect on median lifespan in male mice! This is a question I will take with me when I interview Richard Miller. Thanks for pointing this out. Will be interesting to hear what other people in the forum thinks about this.
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That by increasing energy levels yes, but I don’t think it affects the expression of SLC25A1 (aka the Citrate Carrier).
I’m titrating up my rapamycin dose slowly, so I’m out of sync right now. But, My first 6 weeks and my intended max dose will sync up with my weekly 42 hour fast. As in I will take the rapamycin about 2 hours before the fast ends. I wasn’t thinking about glucose, I was thinking about autophagy. I should be getting some autophagy at that point and then the rapamycin kicks it up, maxes out, and then I can have a salad.
Speaking personally I would be inclined to take Rapamycin at the start of the fast or midway through rather than near the end. If you take it 2 hours before the end the peak level of Rapamycin may not occur when fasting at maximum you will have only 1 hour of overlap.
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I think it’s more due to the SASP?
Rapamycin is known to be effective in suppressing senescence and the senescence-associated secretory phenotype (SASP).
Its one of those situations where we need to agree to disagree.
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I always fast for 18-24 hours before dosing with rapamycin (my rule is, I wait 6 hours after my last meal to start “counting” fasting hours, to make sure my glucose and insulin are given time to return to close to basal levels), then fast for at least another 12, but I just go as long as I can. I try to do it on my off days, it’s easier for me to not eat when I’m off, and I can also take a long easy walk, which I’ve heard also assists in keeping blood glucose levels down.
Okay, you and @John_Hemming have convinced me. When I get to my target dose, I’ll take rapa on Mondays (I eat dinner Sunday and then fast until noon Tuesday every week, until Wednesday during the first week of the month).
If one planned to take a slightly larger Rapamycin dose (say 6+mg) every two weeks, would it make sense to fast for two days around the Rapamycin dose to control glucose levels instead of metformin?
I personally don’t see fasting as that difficult and I’d rather not take metformin (or other medication) around my Rapamycin if I can fast instead (since I don’t understand what other benefits the metformin would bring me as a person who eats low-carb anyway). I believe @DeStrider mentioned in another thread that metformin helps manage lipids as well (which I see as a personal benefit). I’m not thrilled about metformin making muscle gains more difficult. I know the ITP showed a synergistic benefit with Rapamycin, but perhaps it is at least partially due to managing glucose levels (which I can do with a fast). Fewer medications is a plus for me.
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What’s the purpose of a 36 hr fast?
Yes, I believe that the main benefits with the combination of Metformin with Rapamycin is the reduction in blood sugar. We can see this from the Rapamycin study done with diabetic mice where the mice had decreased lifespan with Rapamycin because it inflamed their diabetes. The mice from this trial primarily died from inflammatory causes.
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