From the studies I have seen, it extends the lifespan of all mammals it has been tried on. I doubt humans would be the exception. While not an early adopter, age-wise, I am betting my life on it.
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Well, if anything we would have known by now. I started couple years ago but there are others in these boards that have been taking Rapa for over five years, and I haven’t heard anything bad (other than the slight increase in glucose and lipids in some people).
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I’m sure you are not suggesting that, in the history of pharma, the serious downstream consequences of all drugs were uncovered within a five or even a 10 year period.
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The good news is that rapamycin has been in use for about 27 years now, mostly for organ transplant patients… so the data is reasonably good (admittedly in patients with complex medical histories, typically).
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I’m personally optimistic as well but I believe that the claim, “. . . not impossible that a currently unknown problem will emerge” is one that a rigorously skeptical scientist should hold based on current evidence. The generalization that rapamycin has extended the lives of all mammals it has been tried on (implying something equivalent to a RCC) substantially exceeds current evidence as any deep dive will reveal. Even though claims about mice are high validity, they are not without exception and claims to cross-mammal generalizability remain unproven.
As one LLM summarizes:
Tier 1 (Completed lifespan data, credible): Mice, rats. But even here there are meaningful footnotes. In one accelerated-aging model, Ercc1 Δ/- mice, rapamycin failed to improve lifespan or healthspan. In db/db mice, rapamycin actually shortened median survival and increased mortality risk about 1.7-fold. A cancer-prone mouse study also reported that rapamycin failed to increase lifespan once tumors were already established, despite slowing tumor growth. [As rapamycin, advocates, we have offered several, “Yes . . . but” explanations for those findings but they remain invalidations of the general claim. On that point, one might reasonably ask, “But what if my specific genetic makeup is analogously similar to mice on which we observed serious deleterious effects?”]
Tier 2 (Primate data with biomarker / epigenetic aging signals, ongoing lifespan studies): Common marmosets. A completed metabolic safety study in marmosets at UT Health San Antonio showed the drug was well tolerated, which then secured NIA funding for a formal lifespan study in middle-aged marmosets. This is a TBD category, not a claim of proof.
Tier 3 (Healthspan / biomarker endpoints, no completed lifespan study): Dogs, rhesus macaques, mouse lemurs — where the meta-analysis is aggregating more heterogeneous and lower-powered evidence.
As for safety, we do have a great deal of experience with the molecule which, for humans, comes with warnings of serious, life threatening effects with which we are familiar but have largely dismissed due to considerations of dose and context.
The suggestion that because no one in our group has experienced a problem beyond mild BG elevation, etc. embeds several design flaws. It cannot be validly made for obvious reasons going to data completeness and integrity.
Beyond my personal aspirations, it is a statement of epistemic caution to note that when rapamycin is used as a life-extension intervention in humans, it remains possible that currently undetected serious downstream risks will emerge.
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Get on Repatha…, your LDL may go to less than 10.
Is there a relatively cheap way to do that yet?
Are some of you getting non mainstream doctors to prescribe this in the US?
Is there a cheap global market yet?
If you happen to have high lp(a), you have a 50% chance to receive repatha for free as part of a study that Good Labs is going to participate in…
And if paying cash, good rx finally has it discounted… still expensive but it’s a lot less than it was.
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For safety reasons, I would suggest that you don’t take rapamycin. Apparently you will sleep better not taking it.
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Yes, that is what I’m suggesting. Oh well, if something I take today will kill me 50 years later that is fine by me. I’ll be 110 by then LOL. while there is all kind of scenarios and different people act/react differently to meds, to me if a medication I take for a period of say 10 years and I have little or no side effects, I will not question its downstream safety profile. I might have a higher probability of tripping on the stairs and breaking my neck LOL, which is to say anything could happen, but a 10-year period has got to be long enough a trial period for a substance/med to exhibit its side effects and/or its benefits.
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This could be a Motte-and-bailey fallacy. The controversial position is that Rapamycin is unsafe because of unknown risks, and the motte is that an unknown problem could emerge. I know you didn’t say that but it could be seen that way.
The problem with the motte is you can apply that for anything.
Something can be more or less likely depending on how much data you have.
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Understood and thank you @A_User for noting that I did not make that claim, far from it in fact. A point that might be missed for various reasons.
I do apologize for my previous smart-ass post.
I see from your profile why you might have legitimate concerns. There is no linkage that I can find that associates rapamycin with increased squamous cell skin cancer. My experience is quite the opposite. Due to extreme sun exposure in my youth, I have experienced extreme sun damage to my skin. I have had at least two basal cell and two squamous cell skin cancers removed, plus too many liquid nitrogen squirts to be counted. I have been seeing dermatologists for decades.
I don’t know what your rapamycin protocol was, but I have followed Dr. Mikhail Blogoskonny’s protocol recommended in his papers. Paraphrasing: more is better up to the point of intolerance. I have always, since the beginning, taken high weekly doses of rapamycin, generally 8 mg weekly, with grapefruit juice.
My actinic keratoses have disappeared, and I have not had any form of skin cancer since I started rapamycin. I couldn’t be happier with my personal results. I haven’t seen a dermatologist in over two years.
As I posted in 2022:
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Its all good @desertshores. I have always been encouraged by your exceptionally positive experiences with rapamycin. With the exception of increased muscle performance or decreased muscle fatigue while on rapamycin (which resulted in a serious tear of a calf tendon – not the fault of rapamycin but it was indirectly in the causal path), my reasonably mild generalized actinic keratosis remained the same or slightly worsened and my health metrics were unchanged. There are too many risks in generalizing from this experience and I intend to try rapamycin again soon. In the meantime, I have constructed a “Rapa-light” cocktail of mTOR inhibitors, autophagy inducers, and anti-inflammatories (broad, arterial, and neurological) which, together might confer 40-60% of the benefits on paper, albeit shorter acting, but are not supported by research as a combination. My inflammation panel, however, is very low in the important areas and I’m still driven by the general theory that inflammation is somewhere in the causal path of all or most aging functions. My guess would be that your inflammation metrics are low as well. Do you have GlycA and other inflammation data?
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I’d also back this up by saying that they also reported some apparent negatives of Rapamycin in the marmosets: Rapamycin *worsens* osteoarthritis in non-human primates (BioRxiv) by Adam Salmon, etc - #45 by qBx123Yk
Many caveats - high dose, chronic dosing, 1mg/kg/d, only statistically significant in females etc. But still - it just shows that Rapa isn’t 100% good news.
Still, I definitely wouldn’t consider a weekly dose to be dangerous in any way. My blood markers and my wife’s responded to 2mg/week, so it certainly does something at that dose. But, for context, there are plenty of other interventions which could have consequences greater than taking Rapamycin. For example, air pollution is now one of the top environmental causes of poor health and early death. So living in a better place, running air purifiers in your bedroom etc, might end up being more important than using Rapa in the long run.
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Weren’t we supposed to be dead because of air pollution 50 years ago LOL. I recall in 1991 in one of my classes and the professor (Marxist btw) was saying that by year 2000 everyone will have to carry an oxygen tank in every major city (in order for them to survive because of air pollution). Yeah, air pollution will not deduct one single day from your life span unless you decided to breathe right out of your car’s tailpipe LOL. Having said that yes, I absolutely love it when I’m on top of a mountain in Colorado or in upstate New York, but I doubt I’ll live any longer if I decided to move on those slopes as opposed to where I’m living right now. A much bigger concern IMO is chemicals in foods and household products as well as who the hell knows what’s in our drinking water LOL.
I have reflected on the issue of air pollution myself because I think (impression only) I feel better when the air purifiers I have at home are running. I engaged Claude in an extended dialogue on the relative contribution of controllable environmental factors in longevity. This list below doesn’t do the full conversation justice but is interesting.
Controllable longevity levers, listed in declining order of effect for a typical US adult: (city of residence matters)
- CV fitness (exercise)
- Diet quality (especially reducing ultra-processed food, increasing fiber)
- Sleep (duration and quality)
- Psychological stress and social connection
- Air quality (especially indoor; radon in particular)*
- Water quality (PFAS, lead)
- Pesticide exposure
- Most dietary supplements (with deficiency-correction exceptions)
- I have elevated levels of radon in one of my homes and have had to undertake mitigation efforts. Everyone should check their radon in their home across the seasons, rainy periods often being the worst in some locations.
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Yes, I also believe that inflammation, sometimes called The “Inflammaging” hypothesis, is one of the major causes of aging.
ChatGPT:
The “Inflammaging” hypothesis
The concept was proposed around 2000 by gerontologist Claudio Franceschi.
It proposes that aging organisms gradually develop persistent, low-grade systemic inflammation even without infection.
Key features observed in older adults include:
- Elevated inflammatory cytokines (e.g., IL-6, TNF-α)
- Higher levels of markers like C-reactive protein (CRP)
- Chronic activation of immune pathways such as NF-κB
- Increased inflammatory signaling from senescent cells
This inflammatory state correlates strongly with:
- cardiovascular disease
- diabetes
- neurodegeneration (e.g., Alzheimer’s)
- frailty and disability
Because of these links, many geroscientists consider chronic inflammation a key biological mechanism connecting aging to age-related diseases.
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One of the things I use regularly is “red light therapy” (photobiomodulation).
While I can’t find any large human RCTs, studies support the theory that PBM reduces inflammation. There is little downside apart from the initial investment cost.
Spending some time under the red light is soothing to me, if nothing else.
“However one of the most general benefits of PBM that has recently emerged, is its pronounced anti-inflammatory effects. While the exact cellular signaling pathways responsible for this anti-inflammatory action are not yet completely understood, it is becoming clear that both local and systemic mechanisms are operating. The local reduction of edema, and reductions in markers of oxidative stress and pro-inflammatory cytokines are well established.”
Mechanisms and applications of the anti-inflammatory effects of photobiomodulation
The interesting part of the drug study was that the benefit of reducing inflammation occurred without lowering LDL cholesterol.
“Outside of overt inflammatory illnesses inflammation is a response that is beneficial to a number of tissue insults. Modulation of inflammation has, with almost all agents used, come at the cost of side effects, either directly attributable to the reduction in inflammation/immunosuppression or off-target effects.”
Side effects of PBM are almost nonexistent unless you stay under the light too long.
The Canakinumab Antiinflammatory Thrombosis Outcome Study trial—the starting gun has fired
Residual inflammatory risk is a significant determinant of recurrent cardiovascular risk
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