Self-Reported Data From Several Hundred Rapamycin Self-Experimenters

Rapamycin is arguably the best of the many calorie restriction mimetic small molecules, treatments that can provoke some of the sweeping, favorable metabolic and cellular changes produced by a reduction in calorie intake. The data showing a modest slowing of aging in mice with rapamycin treatment is robust and well replicated, albeit only producing a 5-10% extension of life span, much less than has been shown to be possible via forms of calorie restriction. Like calorie restriction, rapamycin upregulates the cellular housekeeping process of autophagy, but there is much more going on under the hood for both of these interventions.

Is rapamycin better than exercise for longevity? In mice, yes. In humans, who knows? No-one has yet devoted the time and funding to completing a robust clinical trial of rapamycin aimed at evaluating late life health and life expectancy, though the PEARL trial, funded by philanthropic donations, is a step in the right direction. Another step one can take at lesser cost than a clinical trial is to survey some of the many people who are taking rapamycin in the hopes that it will slow aging. Thus we have today's open access paper. While self-reported data is of generally poor quality, for all the obvious reasons (and perhaps especially so in this context!), it is sometimes possible to learn from it, given a large enough study population. The one thing I'd be inclined to take at face value is the reporting on side-effects, for example.

Evaluation of off-label rapamycin use to promote healthspan in 333 adults

Rapamycin (sirolimus) is an FDA-approved drug with immune-modulating and growth-inhibitory properties. Preclinical studies have shown that rapamycin extends lifespan and healthspan metrics in yeast, invertebrates, and rodents. Several physicians are now prescribing rapamycin off-label as a preventative therapy to maintain healthspan. Thus far, however, there is limited data available on side effects or efficacy associated with use of rapamycin in this context. To begin to address this gap in knowledge, we collected data from 333 adults with a history of off-label use of rapamycin by survey. Similar data were also collected from 172 adults who had never used rapamycin.

Rapamycin users generally reported perceived improvements in quality of life since beginning off-label use of rapamycin. Ratios of greater than 3:1 in agreement were observed for self-reported improvements in health, happiness, brain function, feelings of youthfulness, confidence, calmness, anxiety, and generalized aches and pains. Interestingly, greater than fivefold more rapamycin users agreed with the comment that "family/friends have commented that I look good" than disagreed, suggesting that these perceived self-benefits may also be apparent to others.

Rapamycin use by organ transplant patients is associated with a long list of potential side effects. Interestingly, among survey respondents, only mouth sores was significantly more prevalent in rapamycin users compared to non-users. The lack of apparent side effects associated with off-label rapamycin use here is also consistent with prior reports that once weekly administration of 5mg of the rapamycin derivative everolimus has side effects comparable to placebo among healthy older adults.

This study has several limitations that make the data less reliable than what would be obtained from a double-blind, randomized clinical trial. The self-reported nature of the data and the possibility of unintended bias in the participant pool reduce confidence that these results would be recapitulated in a larger, more heterogenous population. In particular, we cannot rule out the possibility that the population of rapamycin users is self-selected against people who started taking rapamycin and stopped because of negative experiences; however, we attempted to recruit as broadly as possible to include such individuals both through social media and through direct recruitment of prior patients who had been prescribed rapamycin in the past.

It is also possible that individuals taking rapamycin off-label are more likely to practice healthy lifestyle habits or take other substances that could confound this analysis. We attempted to evaluate this and found no major differences between groups. Indeed, both rapamycin users and non-users in this study appear to be atypical in that they report higher rates of exercise and healthy dietary habits, lower body mass index, and lower rates of alcohol consumption and tobacco use, relative to the general population. It is possible that potential benefits and side effects from off-label rapamycin use would be different in a less healthy population.


One thing to keep in mind is that not everyone can do exercise or has the will power to follow a strict CR. So even a modest imitation can add up to millions of man-years of extended health/life span

Posted by: Cuberat at May 29th, 2023 4:55 PM

TNF-α blocker MyMD-1 (Isomyosamine) markedly outperformed rapamycin in a mouse longevity study, make it an attractive alternative, especially if MyMD-1 superiority proves to be reproducible. Commercial efforts are currently evaluating the effectiveness of MyMD-1 in Phase II studies for treating sarcopenia/frailty.

Posted by: Dmitry Dzhagarov at May 30th, 2023 6:53 AM

Which "business model"?

Posted by: ML at May 30th, 2023 11:58 AM


Here is a list of natural TNF-α inhibitors, ordered based on available scientific evidence and their potential effect size:
Boswellia serrata (Frankincense): Boswellia serrata extract has shown promising anti-inflammatory effects and inhibitory activity against TNF-α.

Curcumin (Turmeric): Curcumin has been extensively studied for its anti-inflammatory properties, including the inhibition of TNF-α production and activity.

Ginger: Ginger contains bioactive compounds with anti-inflammatory effects, including the potential to suppress TNF-α production.

Resveratrol: Resveratrol, found in grapes and red wine, has shown anti-inflammatory properties and the ability to inhibit TNF-α production.

Green Tea: Green tea polyphenols, particularly EGCG, have demonstrated anti-inflammatory effects, including the inhibition of TNF-α.

Omega-3 Fatty Acids: Omega-3 fatty acids, commonly found in fatty fish and certain seeds, have been associated with reduced inflammation and may modulate TNF-α levels.

Quercetin: Quercetin is a flavonoid present in various fruits and vegetables. It has shown potential anti-inflammatory effects, including the inhibition of TNF-α.

Black Cumin (Nigella sativa): Black cumin seeds and their active components have exhibited anti-inflammatory properties, including the inhibition of TNF-α production
Here is a list of commonly used TNF-α inhibitors ordered alphabetically:
Adalimumab (Humira): Adalimumab is a widely prescribed TNF-α inhibitor used to treat rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, and other autoimmune conditions.

Certolizumab pegol (Cimzia): Certolizumab pegol is another TNF-α inhibitor used to treat rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and Crohn's disease.

Etanercept (Enbrel): Etanercept is a fusion protein that binds to TNF-α and inhibits its activity. It is prescribed for rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and plaque psoriasis.

Golimumab (Simponi): Golimumab is approved for the treatment of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and ulcerative colitis.

Infliximab (Remicade): Infliximab is administered intravenously and is used to treat rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, and psoriasis.

Posted by: Jones at May 31st, 2023 3:36 AM
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