Are there any studies showing Rapamycin lifespan extension in animals from weekly dosing?

There are multiple studies showing that Rapamycin extends lifespan when mice are taking it every day in high doses (example: NIA ITP studies - the highest dose was the most effective)

It is recommended to not take Rapamycin more than once per week because of mTorC2 inhibition

Do we have data that once a week extends lifespan in any animal?

I’ve found one study:

Here, in female mice, 2 mg / kg once every 5 days extended lifespan of mice by 2.3% (median) and 15.6% of maximum lifespan - it is much lower than 15% median lifespan extension from NIA ITP from continuous dosing (when they excluded mice dying from dermatitis, lifespan extension was 7% instead of 2.3% - but maybe mice died from dermatitis partly because of Rapamycin - we don’t know)


EDIT: RapamycinCurious explains below why my response is too simplified.

The reason humans use weekly dosing vs mice daily is because mice have about 7x the metabolism we have. (Someone correct me if I’m wrong)

Basically the 5 half lifes of rapamycin get excreted before it’s the next day and the mice will be ready for the next dose. Humans have to wait a whole week or two for it to be out of their system.

I know this does not answer your question, but I figured you would like to know why humans dose weekly.


That is, unfortunately, the only paper. And as I’ve pointed out before, female mice get more benefit from rapamycin than males do, so weekly dosing may be even less effective in males — unless that is somehow counterbalanced better in males from preserving glucose regulation.

That’s a very clever thought, but not how it actually happened. Instead, it was based on a combination of biochemical modeling and testing of different dosing regimes in Joan Mannick’s original human trial:

2014 paper : mTOR inhibition improves immune function in the elderly

  • Peter read this paper on Christmas Eve and “couldn’t believe ” what he was reading
  • Lloyd, Joan Mannick, and team began the project back in 2010

Pre-work leading up the 2014 experiment :

  • The had pre-work to do before getting to the actual project:
  • 1 | They reviewed the existing literature
  • 2 | They then looked at some other work that had looked at drug levels in cellular systems necessary to partially, or fully, inhibit the target
  • 3 | They had to look at a lot of different cells because the sensitivity of the TORC1 complex to the drug is different in different cells
  • 4 | They then did modeling to understand whether low doses and certain dosing schedules could yield exposures in people that would partially or fully inhibit TORC1, yet give less than assay trough levels to help ensure safety in the healthy volunteers
  • This prep work was necessary because before Joan Mannick brought the program to the decision board of the company to request millions of dollars, they needed answers to questions like…
  • What dose do we use?
  • How frequently do we give it?
  • How long do we treat people?
  • What do we measure?
  • How do we answer the question clearly?

The drug : RAD001 (aka everolimus–which was already FDA approved for renal cell carcinoma)

-Four arms in the study :

    1. Placebo arm
    1. Group that gets 0.5 mgs of RAD001 daily
    1. Group that gets 5 mgs once a week
    1. Group that’s gets 20 mgs once a week

A “clever design” because…a) the weekly doses 5 mg vs. 20 mg answers both efficacy and toxicity questions as they pertain to that dose, and b) the 0.5 mg daily versus the 5 mg weekly is your closest aggregate dose where you get to see if there is a difference in trough
#118 - Lloyd Klickstein, M.D., Ph.D.: Rapamycin, mTOR inhibition, and the biology of aging - Peter Attia


I’ve not come across weekly dosing lifespan trials in mice for rapamycin - just the study you found. Its mixed in with the food typically, so they eat it ad libitum every day of the week.

I needed this, thank you.