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Rapamycin, The Most Promising Aging Intervention

RapAdmin October 25, 2022

It is great to see VitaDOA finally covering rapamycin in greater depth. VitaDAO is a community-owned collective funding early stage longevity research. They fund and help commercialize longevity therapeutics.

It was in 1975 when scientists from Ayerst (now Pfizer) discovered a novel compound called rapamycin (also known as Sirolimus) in bacteria on Rapa Nui (Easter Island) in Chile. In 1999 rapamycin obtained FDA approval for the prevention of acute rejection of renal transplant. Unknown at the time, rapamycin would become the most potent anti-aging drug that humans currently hold.

This is the first article of a two-part series on rapamycin.

Read the Full Article at This Link Below:
VitaDOA: Rapamycin is the most promising aging intervention we currently have

Rapamycin History Infographic

RapAdmin October 25, 2022

A good overview of the history of rapamycin by @Krister_Kauppi

10 Longevity Leaders Who Take Rapamycin

Krister_Kauppi October 11, 2022

Here is a snapshot summary of 10 longevity leaders who take rapamycin and their dosing. See also the in-depth post on Longevity Leaders who are taking rapamycin. Have I missed someone? One interesting thing is that most take it weekly and the average weekly dose for females (4.5 mg) and males (8.66mg) is good aligned with the statistics what 346 people are also doing (5.36mg and 7.93mg - see previous post)

Additional Rapamycin Information Summaries

DIY Rapamycin Toothpaste

RapAdmin September 27, 2022

Periodontal disease (periodontitis) is a chronic oral disease impacting over 70% of older adults, where inflammation of the tissues supporting the teeth results in loss of connective tissue attachment, bone, and ultimately the tooth. The greatest underlying risk factor for periodontitis is age, and its association with other age-related diseases, such as heart disease, diabetes, and Alzheimer disease, highlights the importance of oral health.

Beyond the important health factors, there are also significant visual and cosmetic aspects of dental and oral health. A somewhat common expression for when a person looks “old” is the description of a person getting “long in the tooth”. The reference here is the immediate and significant visual differentiation of younger vs. older people based on the perceived length of their teeth. Two primary factors that make the teeth look longer with age are gum recession and bone loss from periodontal disease. The teeth are the same length, you’re just seeing more of the tooth if structures around them erode. Importantly, both of these issues seem to be reversed by rapamycin. In other words, research suggests that not only can rapamycin improve your oral health, but it may also make you look significantly younger.

Towards these goals, I am trying rapamycin toothpaste to improve my oral health, and prevent oral health issues. In addition to the weekly use of oral rapamycin tablets, I’m going to start trying this rapamycin toothpaste / floss paste, based on the research done previously on rapamycin and oral health: Rapamycin Rejuvenates Oral Health in Aging Mice

There is also a new clinical trial (being done at University of Washington/Jonathan An) trying to further increase oral health with topical rapamycin toothpaste, etc, as outlined in this study initiative: New Study Funded: Towards reversing periodontal disease using Rapamycin

My plan will be to check with dentist measures of tooth pocket depth and compare over time, pre and post treatment.

On the next page I document my step by step process for creating my rapamycin toothpaste and flossing paste (I’ll dip my floss sticks into the formulation prior to use, and before brushing).

Approximately 87% of Rapamycin Users Plan to Keep Using the Longevity Drug

RapAdmin September 5, 2022

Our latest survey of our Rapamycin User’s Group members has been started and in early results suggests that approximately 87% of people who have tried Rapamycin are likely to continue to use the medication (adding up the “Very Likely” and “Somewhat Likely” groups of respondents). An additional 3% say they are undecided, and 10% say its unlikely they will continue with the drug.

Typical discontinuation rates for medication is in the range of 25% to 50% (see sources here and here) so by that measure Rapamycin is doing extremely well. And, the typical medication compliance rate is only about 40% to 50% according to academic studies, so compared to that statistic the rapamycin intent to be compliant with the medication seems very high.

Whatever the case, the vast majority of rapamycin users are saying that, based on the research studies they’ve read, and their personal experiences, they’re going to continue with the rapamycin for the foreseeable future.

See the full survey results here (and please contribute answers to the survey if you are taking rapamycin, as the survey is still open): Rapamycin User Survey #2.

Last week we initiated the first survey on typical rapamycin use patterns and dosing (and please answer the questions if you have not completed the survey yet): Rapamycin User Survey #1.

New Rapamycin / mTOR Clinical Studies Funded By Impetus Grants

RapAdmin August 31, 2022

Rapamycin continues to be the most compelling drug in the anti-aging / longevity field because of its high level of effectiveness, its low cost, and its worldwide availability. Given the many years of successful animal studies, human clinical research is now being initiated at an increasing rate (though it will likely take years for us to see the final results). Today three new human clinical studies were announced and fully funded by the Impetus Grants (in partnership with The Hevolution Foundation). Given the increasingly rapid adoption of rapamycin by thousands of people for anti-aging applications (off-label), there remains an immediate need for a large scale, double-blind, placebo-controlled human clinical study.

Multi-omic biomarkers and mechanistic insights from a clinical evaluation of rapamycin in women

Professor Yousin Suh, Professor Zev Williams (Columbia University)

In the previous Impetus grant round, two teams were awarded funding to conduct a double-blind, randomized, placebo-controlled trial to evaluate the ability of rapamycin to extend women’s reproductive health at Columbia University (PI, Zev Williams) and to reverse periodontal disease at the University of Washington (PI, Jon An). Leveraging these clinical trials, the team from Columbia University will conduct multi-omic analyses of clinical samples obtained from the same study population, with the goals of identifying robust biomarkers and deriving mechanistic insights from a clinical evaluation of rapamycin treatment for women’s health.

Clinical Evaluation of mTORC1 inhibition for Geroprotection: Biomarker Study

Professor Adam Konopka, Professor Dudley Lamming (University of Wisconsin-Madison)

This Phase 2, double-blind, clinical trial aims to identify how mTORC1 inhibition influences physiological and molecular hallmarks of aging across multiple tissues and systems. The team also aims to determine if proposed biomarkers of aging are amenable to mTORC1 inhibition and identify key biomarkers for future geroscience-guided phase 3 clinical trials.

and

Geroprotective effects of rapamycin on inflammaging in older adults with periodontitis

Professor Jonathan An (University of Washington), Professor Vandana Kalia (Seattle Children’s Research Institute)

The project will complete longitudinal immune profiling at a single-cell level in clinical trials of humans taking rapamycin.

Rapamycin Benefits and Side Effects

RapAdmin August 29, 2022

We’ve done our first Rapamycin user survey on the site, with a focus on the short-term benefits and side effects. Measuring any lifespan and/or healthspan improvements will, of course, take much longer to accomplish. You can see the full survey results by going to our survey page. Please answer the survey if you are taking rapamycin.

If you have ideas for future survey topics and measures, please post them and we’ll try to incorporate them in future user polls / surveys.

More in-depth information on rapamycin user-perceived benefits and side effects are included in the Rapamycin Frequently Asked Questions and Answers, here: Anti-aging Benefits of Rapamycin, Personal Experiences and here: Side effects seen with Rapamycin.

Rapamycin-Loaded Microneedles Reverse Hair Loss in Mice

Elizabeth_Kirby August 16, 2022

Rapamycin, one of the most promising geroprotective drugs that was originally used as an immunosuppressant in transplantation patients, is now being tested for many uses, including hair regeneration. One study found that not only does rapamycin stimulate hair regrowth, it can also partially reverse hair graying. EGCG is a polyphenol found in green tea and a potent antioxidant that has shown effectiveness against various conditions, including androgenic alopecia.

I hope it works in people too, and there is data that suggests it likely will: Rapamycin for Hair Growth and Hair Pigmentation

And this could be combined with the minoxidil oral medication that seems to have very good effects, as recently reported: Minoxidil Tablet, not lotion, for Hair Growth and there are other drugs (in a topical application) that seem to revive stem cells and reverse gray hair. Details here: Reverse Gray Hair, Hair Repigmentation

Research Paper Here:
RapamycinMicroneedlespharmaceutics-14-01404.pdf (3.7 MB)

Rapamycin Coverage in Podcasts

RapAdmin August 1, 2022

Here are a few recent podcasts that touch upon rapamycin; below I’ve linked directly to the section on rapamycin in each video.

A good intro and overview of rapamycin by Peter Attia if you’re new to the topic. And Valter Longo provides a contrarian view on rapamycin (at least contrarian to what most of at this site believe). The next in the series is the recent Tim Ferriss podcast with Matt Kaeberlein that covered a lot of rapamycin research, and the last podcast link is the StemTalk podcast interview with Matt.

And if you have questions about rapamycin, be sure to check our Rapamycin Frequently Asked Questions and Answers section. Its updated regularly, and you can always reach it at the top of the homepage of the site (on desktop/laptop and tablet computers, but not visible on phones).

And if you like podcasts, be sure to visit our full list of them: The Best Podcasts Focused on Health and Longevity.

Peter Attia on Rapamycin (on Rich Roll Podcast)

Valter Longo on Rapamycin (on Rich Roll Podcast)

Matt Kaeberlein on Rapamycin (and more) (on Tim Ferriss Podcast)

Matt Kaeberlein on Rapamycin (and much more) on the StemTalk Podcast

https://www.ihmc.us/stemtalk/episode-139/

New Longevity Podcasts: The Longevity Forum

RapAdmin July 15, 2022

The Longevity Forum podcasts look interesting. I had not heard of them before, but they seem to cover everything from longevity biotech, to longevity inequality, retirement and much more (and in some cases covering similar areas as does the Stanford University Longevity Podcast).

In the latest Longevity Forum podcast (see link at bottom of this post) we hear from Kristin Fortney at BioAge who we’ve covered here and here, and James Peyer at Cambrian BioPharma here. As might be expected, rapamycin is a topic of conversation; in this case because Cambrian is hoping to come up with a similar mTOR inhibitor that can provide greater inhibition and fewer off-target effects.

This most recent podcast got me thinking about how the typical person here in our forums who is interested in anti-aging (longevity) drugs might best take advantage of the progress in human testing of these new compounds as these companies work through, report on, and ultimately complete their clinical testing programs.

It seems that one way that individuals might be able to get faster and lower cost access to something functionally similar to these new drugs being developed by BioAge and Cambrian (and many other longevity biotech companies) is to identify the pathway / targets of the drugs that they are putting through clinical trials, then identify other drugs that have already been FDA approved that target the same pathway with similar or better efficacy. Ideally, of course, these approved drugs would already be off-patent, and therefore inexpensive.

As an example, BioAge labs discusses on their website their drug development pipeline. Regarding one of the specific drug candidates they note:

“Apelin is a small secreted peptide hormone that regulates multiple aspects of muscle physiology, including cell growth and survival, regeneration, and repair. BioAge’s analysis of our proprietary longitudinal aging data revealed that higher apelin signaling activity correlates with improved muscle function, reduced frailty, and longer lifespan. Apelin levels decline with age, and activation of apelin signaling reverses age-related sarcopenia in mice. BGE-105, an oral agonist of the apelin receptor APJ, could ameliorate muscle aging”.

Perhaps there are already small molecule drugs on the market today (for other indications) that are an agonist of the apelin receptor APJ. If we can identify these drugs (that may be generic, like rapamycin and everolimus) we may be able to get access to similar drugs at much lower cost, and much earlier than waiting for FDA approval of the proprietary compound from BioAge.

Similarly, BioAge has in-licensed a drug they call BGE-175, a DP1 receptor antagonist discovered by Shionogi & Co based in Japan. BioAge has identified it (through their multi-omics screening process) as a good potential drug for reversing or countering immune system aging. The drug was originally developed for treatment of asthma and the Japanese company took the compound successfully through phase 2 human clinical trials in Japan (so we know its safe), but then the drug failed in a phase 3 trial for asthma. If it looks like BGE-175 is effective at Immune system aging, then biohackers could look for other drugs that are also DP1 receptor antagonists, that might function in the same manner and with the same benefits as BGE-175.

In essence, we biohackers could take the reverse approach that Cambrian is doing with their mTOR inhibitor effort. Whereas they have seen the success of rapamycin in longevity and are seeking to find a molecule that is even better than rapamycin with lower side effect that they can patent. Biohackers can follow their research, then look for preexisting drugs (e.g. in the Anti-aging Drug Database or other drug pathway databases) that target the same pathways or receptors, and would likely provide similar benefits to the new molecules that companies like BioAge and Cambrian are identifying, but earlier and at a fraction of the cost of the new drugs.

LongevityForum website: https://thelongevityforum.com

Latest Podcast:

Kristen: “We’re just at the tip of the iceberg, and there are a lot of promising, complementary mechanisms that can work together to impact aging."