Everolimus 3x more effective than Rapamycin?

#1

I’ve read in a few places that Everolimus is more effective at extending mouse lifespan than Rapamycin by around three times. This is thought to be because it’s more of a “pan-mTOR inhibitor”; that is to say it blocks all the actions of both mTORc1 and mTORc2, where as pulsing Rapamycin only partially inhibits mTORc1 (in doses such as once a week for six weeks with a four week break).

What opinions and evidence do people have about this?

Is it possible to get Everolimus commercially? Has anyone experimented with it and what doses are considered safe in humans?

1 Like
#2

I don’t believe that there have been any mouse/ rodent everolimus lifespan tests - so if you’ve seen any, please post them. Generally I think people / researchers expect there to be no difference in terms of lifespan effect of everolimus vs. rapamycin / sirolimus.

The research I’ve seen seems to suggest that increasing mTORC2 (not inhibiting it) increases lifespan - you can search the forums for past discussions on this topic. Blocking mTORC2 generally is suspected to be the cause of many of the negative side effects of rapamycin when used on a daily basis, at higher dosing… so I’m not sure why pan-mTOR inhibitors are good for longevity - please post links or research.

Everolimus is easily available from the same vendors that sell rapamycin / sirolimus. See this thread about people using it: Everolimus instead of Sirolimus / Rapamycin? Anyone else trying?

2 Likes
#3

Ok, according to Google Bard this paper:

https://www.nature.com/articles/nature12100

Makes the following assertions:

  • Everolimus increased median lifespan by 37% in mice, while rapamycin only increased median lifespan by 23%.
  • Everolimus had a more favorable metabolic profile than rapamycin, with less of an impact on glucose and insulin levels.
  • Everolimus was more effective at extending lifespan in both male and female mice.
  • Everolimus was more effective at extending lifespan in mice of all ages.

But there is a paywall wall so I can’t verify. Also I’d be interested to see who did the research, was it the company developing Everolimus?

1 Like
#4

Sci-hub is your friend. Here is the paper:

https://sci-hub.wf/10.1038/nature12100

I’ve found that ChatGPT makes a lot of shit up when it comes to papers referenced… perhaps the same is true for Bard…?

3 Likes
#5

Hmm… I can’t find this figure anywhere. I think Bard is hallucinating…

And yes, Bard makes shit up.

2 Likes
#6

In fact sirolimus/ everolimus/ rapamycin aren’t even mentioned

1 Like
#7

Yup, most likley my bad for not checking this stuff. Apologies. It was a late night search and I’d not cross referenced.

2 Likes
#8

The lawyers below learned the hard way, that it is best to read the cited sources of AI’s assertions.

3 Likes