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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Notice that the references frame inflammation as exacerbating or contributory to ASCVD but more as an accelerant and not necessary to as part of the causal chain. It think it may be causal. The evidence is thin because few studies have examined this specific question and generally not thoroughly. Correlational examinations tend to show that inflammation is a significant accelerant in ASCVD. Several studies suggest that only ~20% of significant ASCVD events occur in patients with low inflammation. However when you examine the studies, you see a high level set for the “low inflammation” binary and you see that the classification was made on the basis of a single marker; e.g., CRP<0.10. The is contrary case evidence is interesting. Some individuals identified with exceptionally high levels of destructive lipids have normal arteries and no ASCVD but are distinctive for their very low levels of inflammation. At least one other study obtained better results with an ASCVD population by lowering inflammation than by lowering targeted lipids. My view at the moment is that if your MPO and Lp-PLA2 values are in the lowest decile, your lipid profile, including Lo(a) is virtually irrelevant to the consideration of whether you will develop atherosclerosis. You will not. It remains a step of some distance from there to finding that we would be better off eliminating the sources of arterial inflammation than managing serum lipids and yet another step to concluding that such a strategy could result in the regression of some forms of existing arterial disease.
I think in fact the key interleukin is il-10 which is part of SASP, but is considered anti-inflammatory. However, there is evidence that it causes senescence and AIUI that is through a reduction in the expression of SLC25A1 via NF kappa B. (reduction) operating through the Janus Kinase.
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So the link between air pollution and mortality has been known for 70 years. About as long as smoking.
The latest reference I have is from MIT and states that 200,000 premature deaths annually in the US from air pollution. Many of these are from CVD and the point is that these deaths occur earlier but presumably would have happened anyway - just 10 years later (on average).
Radon is responsible for 21,000 US cases annually and presumably many of those don’t die even if most do.
Now radon may also contribute to early death from other things but lung cancer is the only thing I ever hear about.
So I agree with Claude on the ranking but not sure that Radon is the main issue. We have air purifiers in all the bedrooms. My city is slightly above US average on PM2.5.
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Right. It is a little ambiguous but I took Claude’s reference to radon to apply to indoor pollution as a particularity. At a time when so many people smoked, I would guess the reference would be to second hand smoking, etc. One breakout on attributions is:
The primary contributors are road transportation, responsible for roughly 53,000 deaths, followed closely by electric power generation, which accounts for about 52,000 deaths.
Other significant sources include industrial activities, contributing approximately 41,000 deaths, and commercial and residential sources (such as commercial solvents, heating, and in home cooking), which cause deaths primarily in densely populated coastal regions. Smaller but notable contributions come from marine transportation, particularly in Southern California (approx. 3,500 deaths), and rail transportation, which has a comparatively slight and uniformly distributed impact. Per capita, I would guess, radon will show great regional variations ranging from very high to virtually non-existent. I have dealt with radon in several homes and had many others where radon was measured only at the background level for the elevation, etc.
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- Air pollution is now the second leading risk factor for death worldwide behind high blood pressure, and ahead of tobacco and poor diet.
This is not even cutting edge stuff. Here’s a paper from 2010:
https://www.ahajournals.org/doi/10.1161/cir.0b013e3181dbece1
PM2.5 causes systemic oxidative stress, endothelial dysfunction, autonomic imbalance, and low-grade vascular inflammation
And aside from death, around 30% of childhood asthma is attributable to car exhaust NO2.
Up to 23 million annual asthma emergency room visits globally are attributable to ozone, and 5–10 million attributable to PM2.5.
And for cancer, PM2.5 was formally classified as a Group 1 human carcinogen way back in 2013. 370,000–450,000 lung cancer deaths per year are due to PM2.5, which is about 15–20% of global lung cancer mortality.
And more worryingly, https://pubmed.ncbi.nlm.nih.gov/37020004/ showed that PM2.5 promotes EGFR-mutant lung adenocarcinoma in never-smokers. It can explain around 15% of the lung cancers in never-smokers.
There are also links to diabetes: https://www.thelancet.com/journals/lanplh/article/PIIS2542-5196(18)30140-2/fulltext That’s a paper about data from 2016, showing ~3.2 million T2D cases per year are attributable to PM2.5.
For kids, air pollution is associated with 2.7–3.4 million preterm births per year, and ~16% of low-birth-weight infants globally (https://www.sciencedirect.com/science/article/pii/S0013935123024416)
I suppose as somebody interested in longevity, you’re worried about dementia. Well https://www.bmj.com/content/381/bmj-2022-071620 showed that every 2 μg/m³ long-term PM2.5 increases all-cause dementia with a HR of ~1.04.
The evidence seems to weigh air pollution much more strongly than those. And especially water. If you live in a first-world country, your water is just fine. I asked Claude to integrate the findings, and it reckons that total deaths from chemicals in drinking water (lead, arsenic, PFAS etc) are responsible for 3-5% as many deaths as air pollution. Even if you take in total unsafe water (like bacterial contamination, poor sewerage etc), then it would be 20% of air pollution.
It also gives a nice explanation:
Dose and duration. You inhale ~11,000 liters of air per day versus ~2 liters of water. Even at modest PM2.5 concentrations, total delivered dose of particles and adsorbed toxicants to the alveolar surface is enormous, and the alveolar–capillary barrier is ~0.5 μm thick with no first-pass metabolism. Ingested chemicals pass through gut epithelium plus hepatic first-pass clearance, and most are excreted.
We can actually do some basic maths:
- Resting/sleeping adult: ~5–6 L/min
- Light activity (sitting, light office work): ~12 L/min
- Moderate activity (walking, housework): ~25 L/min
- Heavy activity (running, cycling): ~50–80 L/min
So let’s use 15 L/min as a representative number. Based on USA average levels of 9µg/m^3, it means yearly exposure of ~50mg/year. If you live in Dehli, that is 500mg/year.
During a wildfire, PM2.5 levels can rise to 300µg/m3, which will give you 4.5mg per day
The particles are tiny and don’t weigh much, so a better way might be to think about particle number. In the USA, that would be 10¹¹ to 10¹² ultrafine particles per day deep into your lungs.
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low dose naltrexone would be my go to here
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