Right here’s one longevity examine Everolimus, transgenic EGFR mice.
10 mg/kg/day
Everolimus extended survival in transgenic mice with EGFR-driven lung tumors
https://sci-hub.se/10.1016/j.yexcr.2014.04.012
“The median survival time of the everolimus-treated group (58.0 weeks) was considerably longer than that of the car group (31.2 weeks)” That’s 85% on this metric
Fascinating, mTOR and pMTOR don’t see as suppressed in comparison with car in vivo? Wait what, not mTOR?
” Everolimus suppressed pmTOR and pS6 however not p4E-BP, and elevated pAKT (by way of unfavorable suggestions) in vitro (Fig. 1C). Additionally, everolimus suppressed pS6 however not pmTOR and p4E-BP in vivo (Fig. 3B). Conceivably, everolimus might act on totally different signaling pathways in vitro and in vivo. Our outcomes utilizing transgenic mice recommend that marked suppression of pS6 by everolimus is perhaps essential on this respect”
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New poster on the American Getting old convention this coming week:
Wednesday, Could 18th
Neuronal mTOR signaling controls peripheral metabolism
1:35 PM-1:55 PM
DescriptionNeuronal mTOR signaling controls peripheral metabolismStacy A. Hussong1,2 and Veronica Galvan1,21University of Oklahoma Well being Sciences Heart 2Oklahoma Metropolis Veterans Well being Care System, Oklahoma Metropolis, Oklahoma The mechanistic goal of rapamycin (mTOR) is a central regulator of mobile and organismal metabolism. Discount of mTOR signaling by rapamycin alters organismal metabolism and will increase lifespan and healthspan. Neurons regulate many elements of metabolism. To check the speculation that decreasing mTOR signaling in neurons would impression important elements of metabolism cell non-autonomously, we genetically decreased mTOR complicated 1 (mTORC1) by concentrating on its compulsory part Raptor in neurons of grownup mice. Discount of mTORC1 complicated formation in neurons of grownup mice by 35% or 60% didn’t impression physique weight nor glucose and insulin tolerance, however elevated liver gluconeogenesis and glycogen accumulation in skeletal muscle in affiliation with enhanced train endurance and absent post-exercise hypoglycemia. Whereas metabolic impression of mTORC1 attenuation could possibly be partially recapitulated by mTORC1 knockdown in hypothalamus, publicity of muscle cells to serum from neuronal mTORC1 knockdown animals recapitulated in vivo modifications in gluconeogenesis and glycogen metabolism, suggesting that circulating issue(s) mediate, at the least partially, the cell non-autonomous peripheral impression of mTORC1 attenuation in neurons. Reasonable (35%) however not profound (60%) mTORC1 knockdown in grownup neurons additionally elevated mind glucose metabolism and cerebral blood move, enhanced spatial reminiscence, and upregulated PGC1α. Thus, along with regulating cognitive operate in a non-linear vogue, presumably in a cell-autonomous method, mTORC1 signaling from neurons regulates basal and train metabolism cell non-autonomously in grownup mice. Ellison Medical Basis, Owens Basis, Bailey Household Alzheimer’s Fund, VA 1 IK2 BX003798-01A1, NIA5T32-AG021890, 1 I01 BX002211-01A2, JMR Barker Basis
Speaker
Supply: 2022 AGE Program
Thanks. I attended AGE (just about) and noticed that poster.
Does anybody have strong data on the IC50 of rapamycin – for inhibition of both mTORC1 or mTORC2 – in neurons (or different components of the mind)? Hussong’s work may assist information dosing.
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Ive been utilizing 5mg of everolimus with 500g metformin as soon as per week for 9 months
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Very fascinating. Everolimus molecule dimension is about 5% larger than Rapamycin. And there’s no distinction in cost, so all different issues being equal you’d count on rapamycin to cross the BBB marginally extra simply
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Any unwanted effects? Although that’s nonetheless a reasonably low dose, equal to about 3 mg sirolimus. Do you intend to go greater?
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5 posts had been cut up to a brand new matter: Rapamycin for Eyes
desertshores, you might have shared this elsewhere, however are you able to share your aggressive rapamycin dose?
I began at 5mg/week with no amplifiers apart from EVOO.
Then labored as much as each 14 days at 20 mg. with ruby pink grapefruit juice and EVOO. That proved to be an excessive amount of as I acquired diarrhea each time at that dose. Since then after experimenting with doses that did no trigger subjective unwanted effects I settled on 5mg/ weekly with Bioperine, EVOO and RRGGJ. This I tolerate fairly properly and doubtless provides me an efficient dose equal to fifteen – 30 mg weekly.
The non subjective downside is my present ferritin ranges are under regular. This will not be due to rapamycin, it might be as a result of I get too outdated to offer blood twice a yr. Proper now I’m off rapamycin for awhile till I get my ferritin ranges again into the conventional rang.
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Thanks for the reply. That is very fascinating. I used to be on 24 mg each different week and simply switched to 12 mg each week to experiment and see how I really feel. I’m 58 years outdated and considering of including GFJ to the routine. Apparently sufficient my ferritin has been under regular the previous two labs. I don’t every a lot iron in my food regimen however previously yr it has been within the decrease finish of regular however nonetheless within the regular vary till my two most up-to-date labs.
I’m not too anxious given I’ve been following Mangan’s recommendation and wanting a ferritin quantity in direction of the decrease finish and I additionally donate blood each three to 4 months.
Query for you. What’s your GFJ protocol? How a lot GFJ and when by way of earlier than/throughout/after you are taking the rapamycin?
Thanks
I drink 8-10 oz of Florida’s Pure Ruby Crimson grapefruit juice at about 90 minutes earlier than I take my rapamycin. I additionally swallow my capsules in about 2 tbs of EVOO.
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I’m planning on including grapefruit juice to my routine and seeing if any unfavorable outcomes on labs on bodily points. Thanks for this data.
