Subjectively, this is how I feel, my muscles just “work” on SKQ-1.
“In OXYS rats, disorders in the muscle tissue mitochondrial apparatus appear already at the age of 3 months and by the age of 24 months hypoplasia and atrophy of skeletal muscles are developed. These pathological changes are found to be prevented to a large degree by SkQ1.”
Everything (else) I’ve read indicates that everolimus suppresses mTORC2 more than rapamycin does. A simple PubMed search will confirm this.
“Rapamycin treatment once every 5 days (1×/5 days) had the smallest impact on glucose tolerance, and we therefore selected this dosing schedule for further analysis.”
I had been using a rather high pulse dosing every two weeks and noticed zero effect on my A1c results. When I start again I will be using the pulse regimen.
A good video that covers a new clinical trial using everolimus for longevity, being run by Adam Konopka. This new study is just in the starting phase (as of late 2022). Adam describes the study in detail here in this video (lined up to start at the point where he discusses the study):
Everolimus from India comes in 10 tablet boxes at 10mg. At 2 per day (to get to 12-15ng/mL) that’s a box every 5 days. I’ve read Blagosklonny’s “Rapamycin for longevity: opinion article” where ongoing rapamycin appears to be preferred. So does this mean one should plan on 2 tablets per day for life (morning and evening)? Or for a dosing period? Or… Not clear from this thread. Thanks.
Weekly dosing is the norm for longevity applications. And 10mg everolimus is about 6mg equivalent in rapamycin terms. So 1 tablet per week is probably what most people would take.
The above references of trough levels in the 12 to 15 ng/ml is for transplant patients
I was preparing to start my first dose of rapamycin (Everolimus (Glenmark) 10mg once every two weeks) but just came across this bad news Rapamycin inhibits spermatogenesis by changing the autophagy status through suppressing mechanistic target of rapamycin-p70S6 kinase in male rats
you are on the ball RapAdmin- thank you very much.
What’s the source for the table and the graphs? If it’s not open access, can you make the pdf available?
Are you talking about the images in the first post of this thread?
Also,
From the matt kaeberlein talk yesterday:
Yes: I was replying directly to that post. Does the platform not show that?
It was Stephen Spindler who showed that everolimus robustly extends lifespan:
The money shot is at 10:42, but the whole thing is worth a watch.
With all the other stuff that he showed doesn’t work and his strong methodology, this is an important result.
Lots of other mouse data on everolimus and aging outcomes, though not as much as rapamycin.
Here is some of the source data for the first post (it was over a year ago when I posted it, so I can’t find the exact same paper for the Everolimus chart - but there is a close one here:
Klawitter, Jost; Nashan, Björn; Christians, Uwe (2015). Everolimus and sirolimus in transplantation-related but different. Expert Opinion on Drug Safety, 14(7), 1055–1070. doi:10.1517/14740338.2015.1040388
Full Paper here: Sci-Hub | Everolimus and sirolimus in transplantation-related but different | 10.1517/14740338.2015.1040388
The Rapamycin / sirolimus half-life curve is from the paper below, which is included the bottom of the first post in this thread: What is the Rapamycin Dose / Dosage for Anti-Aging or Longevity?
Pharmacokenetics and Safety of a Single Dose of Rapamycin (sirolimus) in Healthy Males
Just one thing to note that I found as I was looking at these papers again… Everolimus seems to have a different response to being taken with a high fat meal than rapamycin / sirolimus … see table below from this paper:
Everolimus and Sirolimus in Transplantation-Related but Different
Link to exact table in paper.
And, the Pharmacokinetics of Sirolimus vs. Everolimus:
From this direct link to the table
Oral everolimus is absorbed rapidly, and reaches peak concentration after 1.3–1.8 hours. Steady state is reached within 7 days, and steady-state peak and trough concentrations, and area under the concentration-time curve (AUC), are proportional to dosage. In adults, everolimus pharmacokinetic characteristics do not differ according to age, weight or sex, but bodyweight-adjusted dosages are necessary in children.
I found this interesting:
Source: Clinical Pharmacokinetics of Everolimus
Full paper (PDF) below:
00003088-200443020-00002.pdf (160.5 KB)
I read elsewhere you want a fast peak with rapamycin, taking it with a high fat meal lower the peak (Cmax), and increases AUC.
I spoke with rapamycin researcher Adam Salmon this morning… he’s doing the marmoset lifespan studies. I’ll post more when I have time to do a writeup on my interview, but in short, yes, high fat is good to take with rapamycin. Adam believes that all the data strongly suggests that its the AUC that matters most for longevity- all the biggest lifespan increases in mice have been daily dosing.
