The Slow Spread of Off-Label Use for Treatments Shown to Target Mechanisms of Aging

A small number of low-cost and generic drugs have extensive human use and safety data, but also a sizable, compelling body of animal study evidence to either (a) suggest a likely modest slowing of aging, e.g. rapamycin, or (b) demonstrate the ability to target a mechanism of aging to reverse age-related disease, e.g. the dasatinib and quercetin combination, shown to selectively destroy senescent cells. In the US any drug approved for a given use can also be used off-label to treat other conditions. In principle the drug can be prescribed by any physician in this way. This is legal, though tends to require a slow bootstrapping process of education, physician acceptance, gradual gathering of more data for the intended off-label use, and eventual grandstanding and interference by regulators.

It is an important process, though. Not just because it is a path to what are likely significant gains to health for the older end of the population, and not just because it is the only viable way to produce clinical data for generic drugs, as there is no financial incentive for industry to fund clinical trials of these treatments, but also because adoption drives public support for greater funding of research into treating aging as a medical condition, and greater investment in the longevity industry. At present, funding for aging research is a tiny anemic fraction of expenditure on medicine, and the longevity industry is minuscule compared to the broader biotech and medical industry. This is a ridiculous state of affairs given the staggering human and economic costs of aging, the vast and ongoing death toll, the hundreds of millions crippled by degenerative disease.

Philanthropists can play a role in speeding up the evaluation and adoption of low cost treatments like rapamycin and dasatinib and quercetin. Rather than leaving the present slow bootstrapping to run its course, a process that could easily consume another decade or two, matters can be accelerated by organizing informal but well-run trials in a few hundred individuals. The cost of this can be $500,000 to $1,000,000 or so per trial, we within the reach of many longevity-interested philanthropists. As a model, look at the PEARL trial crowdfunded by, an example of how to do something meaningful in this space at a comparatively small expense. Such trials can be followed up with outreach to physician networks and patient advocacy groups, increasing the number of physicians willing to prescribe these treatments off-label. This would be a worthy exercise.

Is the Secret to a Longer Life Already Available at Your Local Pharmacy?

Depending on who you ask, we may be on the cusp of a great leap forward in longevity medicine. "In probably the next three to four years, you will have this pill basket" of anti-aging drugs. Based on the patient's health profile, a clinician could tap into the basket's selections and prescribe something to improve health during their final decades: "Let us see whether we can add 10 more years of a healthy life to you." You'd have to be remarkably bullish to believe those drugs will prove to greatly boost the quality and length of late life in the imminent future. There are doubts that the potential of these therapies will be fully understood - and thus implemented most effectively - any time soon. After all, proper testing would take decades. Yet some experts in the burgeoning field of geroscience are increasingly confident that a batch of different molecules undergoing analysis for anti-aging properties contains game-changers. Among the potential prize ponies are prescription drugs like rapamycin, metformin, and senolytics, alongside supplements like alpha-ketoglutarate and taurine. The aim is to perfect an array of molecules that not only extend the life expectancy of users, but also boost overall health during their final years.

But despite the potentially transformative nature of these molecules, some spectators have found progress to be needlessly slow. "The way our regulatory system is structured, there's just no incentive to do those trials." Because many of the promising candidates are already generic drugs, the rate of research has been gradual. Without serious money to make, even the prospect of a non-metaphorical Holy Grail can't motivate the pharmaceutical industry. The structure of FDA trials are also an awkward fit with geroscience. When testing the efficacy of an anti-aging therapy, what do you measure? There's not a catch-all biomarker. "If we go to the FDA with a blood pressure medication, we measure blood pressure to know if the drug is working or not. With aging, it's really hard to go with what marker you're going to use."

Nonetheless, progress has continued. Closely watching the advance are so-called biohacker communities, online groups that digest any new data to guide their own regimens of potential longevity drugs-typically therapies for other illnesses taken off-label - hoping for a headstart on treatments whose effectiveness will later be fully proven. The search for life-lengtheners has long attracted bunk science and charlatans, and the addition of outsider research - legitimate or not - could give medical experts pause. "That's something that the aging community is really wrestling with right now. Aging has really been pushed to the forefront, which is a good thing. But we're trying to get past the pseudoscience of the Fountain of Youth and that kind of thing."

But even as that tension persists, amateur discourse around these drugs may have the effect of drawing the attention of physicians. A primary feature of digital communities devoted to gerontology is to share where certain therapies may be procured. It provides not just an access point for future users, but it could also serve to reassure prospective prescribers. "There's a small group of them at first. But once they see some of their colleagues doing this - and maybe their colleagues have 100 or 500 patients on rapamycin - then they start to feel comfortable." Thus, as the online community of people allegedly taking these drugs grows, its relationship with the medical community becomes more reciprocal, and a given drug's credibility "percolates through the medical community that way."


I looked for C15 on the site and didnt find anything so i thought you may be interested in this as it's not even a prescribed drug (so not even off label) but has claimed effects on par with Rapamycin.

Pentadecanoic acid (C15:0) is an essential odd-chain saturated fatty acid with broad activities relevant to protecting cardiometabolic, immune, and liver health. C15:0 activates AMPK and inhibits mTOR, both of which are core components of the human longevity pathway. To assess the potential for C15:0 to enhance processes associated with longevity and healthspan, we used human cell-based molecular phenotyping assays to compare C15:0 with three longevity-enhancing candidates: acarbose, metformin, and rapamycin. C15:0 (n = 36 activities in 10 of 12 cell systems) and rapamycin (n = 32 activities in 12 of 12 systems) had the most clinically relevant, dose-dependent activities. At their optimal doses, C15:0 (17 µM) and rapamycin (9 µM) shared 24 activities across 10 cell systems, including anti-inflammatory (e.g., lowered MCP-1, TNFα, IL-10, IL-17A/F), antifibrotic, and anticancer activities, which are further supported by previously published in vitro and in vivo studies. Paired with prior demonstrated abilities for C15:0 to target longevity pathways, hallmarks of aging, aging rate biomarkers, and core components of type 2 diabetes, heart disease, cancer, and nonalcoholic fatty liver disease, our results support C15:0 as an essential nutrient with activities equivalent to, or surpassing, leading longevity-enhancing candidate compounds.

Posted by: Rob at November 15th, 2023 11:31 AM

+1 here here for a D+Q trial put on by the peeps. I would support

Posted by: Gregory Schulte at November 15th, 2023 12:04 PM

It seems most of the Dasatinib patents have expired outside of US, and in a couple of years will expire in US too.

One surprising thing was that the european generic authorization for Dasatinib Accordpharma was retracted by the requesting company.

Posted by: Cuberat at November 15th, 2023 4:03 PM

The C-15 study may have been sponsored Seraphina Therapeutics Inc., which has a pentadecanoic acid (C15:0) food ingredient and supplement on the market.
Touted as an omega 3 alternative, it could be quite interesting,
Those of us that consume grass fed butter and cream every day probably get plenty and don't need a supplement. Butter instead of rapamycin, now that would be something!

Posted by: august33 at November 16th, 2023 10:13 PM

and of course extra Butyric acid too!

Posted by: Rob at November 18th, 2023 4:33 PM
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