#347

Brad Stanfield does a pretty good job of analysing this paper:

And one of the authors on the paper says:

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4 Likes
#348

Peter Attia good agree with everything Brad say about the paper and still he comes to the opposite conclusion. Why take some thing with no proven benefits if there is even a tiny risk?

1 Like
#349

Are there any updates on M Blagosklonny’s health status? Looks like he stopped posting on Twitter at the end of July.

6 Likes
#350

I would love to see a reference for the claim that mTOR is generally higher in mice than humans. I haven’t seen such a reference.

3 Likes
#351

It is a sample size of 1 and it tells us nothing.

2 Likes
#352

I think this is his latest blog on his battle with cancer:

13 Likes
#353

2 posts were merged into an existing topic: Strategies to avoid the grim reaper of Cancer - Part I: Colon Cancer

#356

I am reposting my situation from another thread:

I am in a similar situation. A family member who was cancer free for 5 years and started taking Rapamycin 8 months ago, just had their cancer markers begin to increase again. I don’t know if I can say it was because of the Rapamycin or not given that we were very careful to make sure we were just inhibiting MTORC1.

We’ve been through this many times already where the cancer was is in remission for a few years and then pops back up again, we then do some protocols, and it takes a rest for a few more years. So hopefully it is the same this time around.

I wrote a post about a month ago about some treatment options that helped create the several remissions my family member had, in case you were interested:

If anyone has some insight on Rapamycin for cancer patients in remission or current cancer patients please feel free to share the info with me. As of now, Rapamycin will be continued as the research in the cancer field on Rapamycin on breast cancer is ok, considering that most treatments in cancer are anyways experimenting on yourself.

This is because needed studies do not get funded and because no ethics comitee will approve a real high quality RCT in the cancer field where a control group of cancer patients, would mean they would have to receive no treatment at all in order make a strong correlation and by not receiving any treament the control group would eventually all die.

7 Likes
#357

Hello,

I only intended to post once here introducing myself to anyone interested in longevity coaching / consulting within the context of a nice review I was appreciative for.

But I just hopped on again as I famaliarize myself with what my clients are reading. This thread caught my attention from the tite.

I wrote an opinion piece (which does not say whether or not one should take rapamycin but about his cancer in particular), that I’m posting here in case it’s helpful to anyone.

If it’s inappropriate to post your own posts from elsewhere please let me know and I won’t repeat this error. But here it is, should it be useful or interesting to you all. Kind regards, David:

https://x.com/agingdoc1/status/1676865195891630080?s=20

and in case twitter / X ever goes away (Paste by RapAdmin):

I try to be selective when I provide an opinion. Occasionally circumstances arise whereby opining may do overall good. Recently a member of the Twitter community has publicly declared he has metastatic cancer. This individual has also been on high dose rapamycin. So I have been asked, as someone who has expressed enthusiasm for pursuing translational research whether benefits in animal models extend to people, does this news change my mind?

  • No, not one bit
  • Case reports are uninformative regarding causality.
  • We already know cancer is possible on rapamycin, this is not new.
  • Cancer is stochastic- I have shared data on risk factors because I believe knowing them empowers us to reduce risks. This is NOT the same as cancer elimination. Chance (and unknown, often stochastic risks( will always play a role. Risk is never zero.
  • Indeed as physicians when we tell patients they have cancer and they ask why, most often we can share information on risk factors but usually not why they got cancers. Because we do not know, and it generally/usually for practical purposes unknowable.
  • Model organisms on rapamycin still die. We all do. They just die, on average, later and as far as we can tell in overall better health (except the end).
  • What what do mice, etc on rapamycin die from? In large part the same conditions that are fatal in control animals.
  • The difference in life expectancy between rapamycin and control mice is an average. Some mice live shorter as well as longer. The differences in lifespan is an average. Simply put, being in rapamycin stacked the deck (odds) in favor of a longer lifespan.
  • Back to chance: Mr Rogers was slim and ate his vegetables. Yet he died young, of cancer. Shall we blame his being slim or minding his diet? Or that until the end he had a very disciplined swimming routine? No- case reports simply are not informative in this manner.
  • These arguments can be extended to other agents too, say individuals taking derivatives of niacin for example. Unfortunately we are mortal, and will see the full gamut of pathology sometimes regardless of our best efforts. Our job is to take the best evidence, respond to data & make our best efforts to follow the evidence and our best chances for good health.
  • Rapamycin, additionally has data in both animal models and humans. The human data mostly favors less cancer compared to patients on other transplant medicine. To the extent the human data is mixed in some places, the quality is poor, based on patients who are generally already sick (having transplants, being on other meds including immunosuppressants etc) and also on a very particular high dose daily regimen to boot.
  • We do not have good, reliable data for humans. Apparent outcomes in community based off-label prescribing for geroprotection has if anything been mostly reassuring. To truly understand the relationship of rapamycin with human health we need more, better, rigorously controlled trials. Thus poor data only makes the case stronger for translational research in people. This, and the strong and reliable independently validated and reproducible lifespan extension seen in model organisms compel this research more than ever.
  • Finally, it should be noted that not only do animal models at physiologically relevant doses tend to have cancer later in life, but even in humans rapamycin and related rapalogs are being used as an adjunct in the treatment of several human cancers.
  • Though not a cure, human data suggesting extended relapse free survival for some cases is more a source of hope than concern. Indeed, I am aware of no well conducted RCTs in humans that even very high dose rapamycin (10+ mg per DAY) shortens lifespan vs usual care in cancer patients.
  • Precisely because of animal models and some suggestive data in humans, several low dose rapamycin prevention trials have been proposed.
  • I believe these, and many more should be done. A major point of animal models is to save us time and resources and allow for highly controlled feasible rigorous study design. The results of this suggest when agents warrant our attention.
  • I believe that rapamycin warrants such attention, as the highest effect size (magnitude of life extension) and highly reproduced small molecule intervention in normal, healthy, and genetically diverse, naturally aged mice. So too for a plethora of other model organisms too, not to mention validated in rodents of both genders.
  • Unknowns are not a reason to avoid investigation. They are inevitable. And all our choices of have potential risks and reward.
  • Rather, promising data and unknowns are a reason for investigation.
  • With unknowns cons risks… but also potential benefits. This is how we learn. Science is not s religion. We do not have “faith” in a molecule or intervention. We must test it. We study it, and we follow the data wherever it takes us. Both the good and the bad. We must test our theories to determine where we were right, where we were wrong, and where to go next.
  • This is our way forward. I support geroscience research and all promising work towards improving our health. I will support research in any promising area with potential to improve our health, and am committed to following the data, wherever it takes us, and always with an open and adaptive mind, as new data and evidence present themselves.
  • Not all seemingly promising interventions will ultimately work out- and most will not, sometimes at a great cost - but we must nevertheless roll up our sleeves and do the actual work to determine which ones.
  • We all face sickness or decline and death. Marching ahead is how we make progress. We have left the jungle and created civilizations and modern medicine. We still have far to go. Our limits are only defined by physics, our inherent but expanding capacity, and perhaps most of all the time and commitment to prioritizing progress central to elevating our healthspan and quality of life.
  • So where do we stand now? Progress depends on US. Our reason, our time, our resources- and our commitment.
  • From these data to date, more than ever, I still believe there is a strong case for vigorously supporting rapamycin trials, without delay. I came to Twitter was to do good. Among them I saw an opportunity around drawing attention to rapamycin, which I regarded as having the greatest potential for being validated as a potent healthspan extender in suitable candidates. I felt if it held up to it’s promise, it has the potential to not only be an n exiting target for aging biology, but more fundamentally and profoundly, and across the world a true game changer toward better public health. That was my hope; an inspiration of what might be possible. After all this time, how has my feeling changed about this and rapamycin? Not one bit. -

@agingdoc1

Footnote: Thank you Misha

@Blagosklonny

for your vision, your leadership, and your courage!

24 Likes
#358

Thanks for sharing. I had seen the post on X originally but it was worth reading again. It reminds me of an age calculator in the NYT several years ago that presented a forecast of my death age differently than most. It provided a discrete age when I would die based on my inputs, probability curves, and a random number generator. Each time I ran my numbers I would get a different number because chance or luck was involved. That is how real life works also. Riding my bike on the road I share with trucks is a larger factor in my longevity and healthspan than which supplements I take, I’d bet.

6 Likes
#359

100% Well said Joseph.

4 Likes
#360

Exactly… playing the odds… rapamycin might work… provided I don’t die a stupid death by accident.

Which is actually much more likely with my renewed euphoria and youth energy. Hahaha.

6 Likes
#361

I’m a rare bird in (at least considering myself) being a moderate here. Too many dismiss the concept of adopting practices (that do come with some risk) that are unproven in humans as foolish. And among the community that have chosen, with informed consent, to proceed too often label it a riskless sure thing panacea.

Not only is the data mixed, but so too there is gray in considerations at the personal level- even leaving aside personal reasons why one person may for clinical reasons shift in one direction or the other. This includes willingness to take risk, comfort with uncertainty, and other considerations. It’s implemented in evidence-based financial planning, and medicine should be no different for personalized care.

As you know I don’t prescribe or use my medical license for coaching/consulting, it’s information, expertise etc. And I don’t disclose my own practices either for personal reasons. But what I DO do is speak voraceously that (1) were should be aggressively purusing a translational agenda to test compounds that may extend healthy lifespan in people and (2) individuals are intelligent and can make informed decisions for themselves along with their prescribing provider together.

Regardless what we find, I’m hopeful that advocacy from communites like this can help raise awareness at the funding and regulatory levels in the U.S. and abroad to support the study, validation, and accessability of potential therapies.

Health is the greatest wealth, so we all should be paying attention to this.

8 Likes
#362

A good question is “what is proof” another question is where the risk reward balance lies. Are we picking pennies up in front of a steam roller?

5 Likes
#363

They are the essence of informed choice. I agree, and not easy to answer. But the analogy Peter Attia loves to use for this question is apt indeed.

2 Likes
#364

As Peter says… why not hedge your bets. Its good business and your health and life is the business.

3 Likes
#365

N=1

82+ years old. Retired engineer.

Took “Probabilities and Statistics” in college.

Lives where gambling is king.

Past my shelf life, nothing to lose.

No fear of premature death.

Risky by nature.

Sheep are not my friends.

And, I like hanging out with people that are smarter than me.

16 Likes
#366

People forget. There are risks in venturing into a choice… and risks holding off too. It’s a complex game, but we must remember there are tradeoffs and considerations at both ends @desertshores

9 Likes
#367

@agingdoc On behalf of the community, we are thrilled to have you here. Please feel free to post anything here as you like. We enjoy engaging geoscience intellectuals such as yourself.

Again welcome to the community! :slight_smile:

5 Likes
#368

You need to identify a specific question, however.

Some are: (with my views)
Rapamycin - yes
Metformin - no
Melatonin megadose - yes
Citrate (acetyl-coa) - yes
Ashwaghanda - no
Resveratrol - no

The above are I think controversial