Questions to ask Joan Mannick?

Now in December I will interview one of the world’s leading Rapamycin researchers Joan Mannick in the Rapamycin Longevity Series podcast. She has made and is making a huge contribution to the field with her research around the next generation of mTOR inhibitors. Are there any questions you want me to ask her?

I’m really looking forward to this interview and in the future I’m confident that we will find even better mTOR inhibitors than Rapamycin when it comes to improving longevity. I have heard of some interesting early data in the area. I recently started the Rapamycin Longevity Lab and in next year the goal is also to start moving the field forward around next generation mTOR inhibitors :pray:


Why didn’t higher dosages in her everolimus immunosenesence trial meet the trial endpoint? Was it because of immunosupressive effects, if so does she think a longer washout period would detect a larger effect?

Has there been any study showing everolimus improving mice lifespan, has there been any published study?

What does she think of mTOR inhibitors generally increasing LDL cholesterol levels? Is it this a concern for current and future mTOR inhibitors, if so how can it be prevented?


You’re doing a great service for us all. Thanks so much. I’d be interested in her thoughts on slowing aging with small molecules like rapamycin on top of a healthy lifestyle. If we are doing everything else well (diet, sleep, exercise, stress management, using medication as needed to keep blood and physical markers (BP, HbA1C, apoB, body fatness) in a healthy range), what else can we do, balancing risk and reward? And how would we know if we are improving? Short term vs long term impacts? Are any of the biological clocks ready to help at all?


Do any rapalogs exist that target specific tissues? Would there be health benefits to targeting hyperactivated mTor1 in specific tissues rather than whole body? Do rapamycin or rapalogs already concentrate more in some tissues? If so, why?


@AnUser Great questions! Regarding that Everolimus did not meet the trial endpoint, my guess is that you are refering to her 2009 study?

@Joseph_Lavelle Big thanks Joe! Relly interesting question to take a dig in!

@EnrQay Super interesting questions! I will have a interview with David Sabatini next year and I will also ask him around this topics :pray:


On people to add to your list of leaders who take rapa

Bob Nelsen, one of minds and backers behind Altos Labs

Ned David, multi successful biotech entrepreneur:


I mean the 2014 study where 20 mg weekly didn’t improve immune response as the 5 mg dose (two over the black bar).


:+1: Sorry, yes, I meant the study 2014. The 2009 study was the ITP study.


Were there other post hoc analyses from her trials that were interesting?

Especially did they get any data on how people from their last trial did during Covid pre and post vaccinations? how they did with long COVID? (the recent Matt K et al Survey Study of rapa users showed especially strong impact against long COVID I think)

Edit for @Krister_Kauppi What does she think about the results from that survey by Matt K et al in general?


the jump from Rapa as an”immune suppressant “to “immune modulator / immune rejuvenator” came with Joan’s 2014 study based on the pulsed dosing. Has anyone ever tested chronic dosing of Rapa on the same flu vaccine response?


They did try 0.5 mg daily dosing in the same Mannick 2014 study and it was as effective as 5 mg one time a week.


Thought that same study did? See eg the figure quoted by AnUser above 0.5 a day dosing?

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I forgot about that. It’s such a small dose —not sure it’s apples and apples or if that affects this whole way of thinking a pulsed approach results in a very different result (suppression vs. enhancement)

I tried CHATGPT, here is what I got

I’m interviewing joan mannick, the co-founder and ceo of tornado therapeutics. she has been doing research on rapamycin. Give me 10 provocative questions related to the benefits and risks of healthy people taking rapamycin for longevity

Certainly! Here are 10 provocative questions related to the benefits and risks of healthy people taking rapamycin for longevity that you might consider asking Joan Mannick:

Optimizing Lifespan:
“In your research, have you found evidence supporting the idea that rapamycin could be a viable option for healthy individuals looking to optimize their lifespan? If so, what mechanisms make it a potential longevity enhancer?”

Risks and Side Effects:
“Given that rapamycin is an immunosuppressant, how do you address concerns about potential risks and side effects, especially when considering its use by healthy individuals who may not have existing health issues?”

Individualized Treatment:
“Do you envision a future where rapamycin treatment for longevity is individualized, taking into account genetic factors, age, and overall health? How might personalized approaches mitigate potential risks?”

Impact on Quality of Life:
“While extending lifespan is an intriguing prospect, how do you address concerns about the potential impact of rapamycin on the quality of life, particularly in terms of cognitive function and physical vitality?”

Balancing Trade-offs:
“Given the dual role of rapamycin in suppressing the immune system and potentially promoting longevity, how do you strike a balance to ensure the benefits outweigh the risks, especially in healthy individuals who may not have compromised immune function?”

Long-Term Use:
“Can you discuss the potential challenges and considerations associated with the long-term use of rapamycin for healthy individuals seeking to slow down the aging process? Are there diminishing returns or accumulating risks over time?”

Ethical Considerations:
“From an ethical standpoint, how do you navigate the implications of offering a drug like rapamycin for healthy individuals who might be seeking it for non-medical purposes, such as longevity enhancement?”

Alternatives and Combinations:
“Are there alternative strategies or complementary interventions that you see as potential partners to rapamycin in promoting healthy aging? How might combining therapies enhance their effectiveness or mitigate risks?”

Potential Gender and Age Differences:
“Have you observed any gender-specific or age-specific differences in the response to rapamycin, and how might this influence the considerations for its use in healthy individuals across different demographics?”

Regulatory Landscape:
“Considering the current regulatory landscape, how do you envision the path forward for rapamycin or similar compounds as potential longevity interventions? What challenges and opportunities do you foresee in navigating regulatory approval for such non-traditional uses?”

These questions touch on various aspects of rapamycin research, longevity, and the potential implications for healthy individuals, aiming to spark insightful discussions around the benefits and risks of using rapamycin for promoting healthy aging.


@Neo Great questions! I really liked the Covid part.

@jaakdefour The power of ChatGPT :slight_smile: I usually try to use it to give suggestions for questions. Big thumbs up that you guided it to “provocative questions” :+1:


I have heard about post hoc analysis in passing about her trials but I have not looked into it, neither which trials which it was about.

Sorry, not able to follow this part, can you clarify what you mean?

She has done post-hoc analysis for other trials than the 2014 one for sure, I think for one of the novel rapalogs. The rapalog that failed and made their company stock crash. I don’t know if they have done it for the 2014 trial.

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One on the “business” side:

Can you talk about the growth of Rapamycin/Rapalog sales over the last few years. Is it accelerating. Is off-label use a key driver of growth?
Do “events” such as the release of Peter Attia’s book Outlive (in which he admits taking Rapamycin for longevity) create a discernible step function in the sales?

I wonder if she can comment in a good way on this one. Probably a better question to another guest?

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