Thread by @mkaeberlein

A few days ago I chose to call out a misleading Tweet by my friend and colleague @lamminglab that appears to endorse a flawed interpretation of a new study testing the effects of rapamycin on bone in young mice:

https://twitter.com/LammingLab/status/1426905471638724615

You may wonder, what’s the point?

1/

IMO, one reason for being on Twitter as an expert in #geroscience is to try to prevent misconceptions and misinterpretations that have the potential to damage the field. This appears to me as a classic example of how misinterpretation can potentially do great harm

/2

The study in question used very young mice that are still growing to test the effects of rapamycin on bone. They found that the mice receiving rapamycin had lower bone density. Importantly, no evidence for lower bone quality or bone frailty, but that was not discussed.

/3

The interpretation here suggested these results should raise concern for use of rapamycin clinically to delay or reverse aspects of biological aging. What the paper and the Tweet failed to present is the obvious flaw in this interpretation

/4

Also neglected in the paper and Tweet was data from multiple studies showing that rapamycin in aged mice and rats can reverse age-associated bone loss.

https://twitter.com/mkaeberlein/status/1428375514608062465

/5

If the goal is to understand how rapamycin affects bone deposition and/or resorption in developing/growing mice, this is a perfectly good study. If the goal is to understand effects on aging, it is absolutely the wrong experiment.

/6

I’m certain @lamminglab would reject any grant that proposed to treat young mice with an intervention and extrapolate outcomes to biological aging. In NIH reviewer-speak this is a “fatal flaw”. So, why didn’t reviewers catch it?

And why does this matter for the field?

/7

Rapamycin has a bad reputation due to its historical use at high doses in sick patients, where there are significant side effects. This is used by uninformed and/or intellectually dishonest people to suggest it can't be used at lower doses to target biological aging.

/8

I will continue to refute this misinformation with actual data. Rapamycin at low doses appears safer than most drugs. We and others are actively testing rapamycin in clinical trials and hundreds of people are taking it at low doses with AFAIK no serious adverse events.

/9

Unfortunately, those who want to argue rapamycin is a “bad drug” won't address the actual data. Should we be careful and watch for side effects? Of course. Is there any reason to think we’ll see bad ones at doses under consideration. Nope.

/10

How is this damaging to the field and to patients?

Rapamycin is still the most effective and reproducible pharmacological intervention for delaying/reversing biological aging out there.

/11

Grants don’t get funded and clinical trials don’t happen because of false perceptions around the safety profile of rapamycin. Progress has been and continues to be held back.

/12

Rapamycin should have been tested for Alzheimer’s disease 10 years ago. I know from personal experience that misinformation about the side effects has kept this from happening. The people who spread this misinformation bear some responsibility.

/13

The fact is that even most experts in the field, let alone “experts” in the Twitter-verse, won’t bother to actually look at the data. So, FWIW, I try to pick my battles and clarify misinterpretation/misinformation around rapamycin when I see it.

14/14