The longevity industry has an evidence problem. But the medical establishment has an engagement problem. I am increasingly convinced that both sides are wrong, and the interesting position -- the one almost nobody occupies -- is in the middle.
She was 52, healthy, and she brought a three-ring binder. Tabbed sections. Color-coded. The first tab was labeled "mTOR Inhibition" and contained six PubMed abstracts, two podcast transcripts, and a handwritten comparison of rapamycin dosing protocols from a longevity forum. She wanted to know if I would prescribe rapamycin for anti-aging.
I get some version of this conversation at least twice a month now. The patients are smart. They have done real reading. What they usually lack is the clinical training to distinguish a promising mouse study from something I can responsibly act on.
But here is what I have had to admit to myself over the past two years: what I sometimes lack is the humility to recognize when a patient's reading has outpaced my own.
The PEARL trial changed the rapamycin conversation
For years, rapamycin was the longevity community's most-discussed drug based almost entirely on animal data. Conferences built entire sessions around it. Forums debated dosing protocols with the intensity of religious doctrine. And physicians like me would say some version of "interesting, but we only have mouse data" and move on.
That changed in April 2025, when the PEARL trial results published in Aging delivered the first large randomized controlled trial of rapamycin in healthy humans -- 48 weeks, double-blind, placebo-controlled. Finally, actual data.
The headline: no significant safety differences versus placebo. Reassuring. But the anti-aging signal the community had been expecting? Not there. Not in any clear, generalizable way. Women on the 10mg dose showed increased lean mass and reduced pain -- an interesting sex-specific wrinkle. But as a broad anti-aging intervention? The data does not support it.
I now tell patients about PEARL directly. It is a better conversation than the one I used to have. Instead of "we only have mouse data," I can say: we ran the human trial, and the answer was more complicated than the podcasts predicted. That is how science works. The honest version is more useful than the dismissive one.
The finding that made me reconsider my own skepticism
I used to dismiss longevity medicine more categorically than I do now. I had a comfortable position: the evidence is not there, the supplements are unregulated, the clinics are selling hope. Clean. Simple. And partly wrong.
The semaglutide data forced me to rethink.
In July 2025, a randomized controlled trial showed that semaglutide -- a GLP-1 receptor agonist already FDA-approved for diabetes and obesity -- reversed multiple epigenetic aging clocks. PCGrimAge dropped 3.1 years (P=0.007). PhenoAge dropped 4.9 years (P=0.004). DunedinPACE improved by 0.09 units (P=0.01). This was the first RCT demonstrating that a licensed drug can reverse epigenetic age markers.
I want to be careful. Single trial. Needs replication. Epigenetic clocks are surrogate endpoints, not hard outcomes like mortality. I know all the caveats.
But here is why this data matters structurally, and why it genuinely shifted my thinking: semaglutide already has safety data, prescribing infrastructure, and insurance coverage. If the epigenetic findings hold up, the path to clinical use is years, not decades. Compare that to the TAME trial for metformin, which spent over ten years trying to get off the ground before being effectively absorbed into ARPA-H's FAST initiative. As Nir Barzilai himself has noted, Eli Lilly may beat TAME to a longevity answer with a GLP-1 trial. The molecules with regulatory and commercial backing move faster than the ones relying on academic grant cycles.
I had been waiting for longevity medicine to produce evidence on the academic timeline. The market is not waiting. The global longevity market reached $27.6 billion in 2025, with longevity clinics growing headcount by 37% year over year. More than 45% of consumers and healthcare providers have adopted at least one longevity solution. The industry is scaling whether physicians engage or not. The question is whether we engage on our terms or cede the conversation entirely.
The five-drug stack and the missed colonoscopy
Last fall, a 58-year-old patient came in taking metformin (off-label, no diabetes), low-dose rapamycin (sourced from an online clinic), NMN, resveratrol, and BPC-157. Five compounds. Monthly cost: roughly $900. He could recite the mechanism of action for each one.
He was also two years overdue for a colonoscopy.
This is the pattern that concerns me most. The psychological appeal of longevity medicine -- the sense of proactive control, the feeling of optimizing -- can paradoxically distract from the preventive care that actually saves lives at a population level. I have had patients skip cardiovascular risk assessments because they were "optimizing NAD+" with a supplement stack. One patient brought in handwritten notes from a podcast episode -- more detailed than any medication history I have ever received from a referring physician -- and had not seen his primary care doctor in three years.
But I have also started wondering whether the dismissive response -- "just get your colonoscopy and stop wasting money on supplements" -- is part of the problem. That patient came to me because his primary care doctor had rolled her eyes at his binder. He did not stop taking the supplements. He stopped seeing the doctor. The eye-roll did not protect him. It just removed him from medical oversight entirely.
What a patient taught me about NAD+
I will admit something. Last year, a patient brought in a paper I had not read. A 2024 RCT published in GeroScience by Igarashi and colleagues that tested NMN in 60 older adults over 12 weeks. The NMN group maintained walking speed, showed improved grip strength, and reported better sleep quality compared to placebo.
I had been telling patients that NAD+ precursor data was "mostly animal studies." That was no longer fully accurate, and I had not updated my position. The patient had. She was polite about it, but the correction was clear.
A 2025 head-to-head comparison in Nature Metabolism further confirmed that NMN and NR both raise blood NAD+ levels after 14 days, while plain nicotinamide does not. These are real findings. Small trials, short durations, preliminary. But real. Dismissing them as "just supplements" is intellectually lazy. I was being intellectually lazy.
That said -- and I told this patient directly -- small positive trials for NAD+ precursors do not justify a $300-per-month supplement habit as a substitute for a colonoscopy. Both things can be true. The supplements might have modest benefits. The colonoscopy might save your life. One of these is more urgent than the other.
Where I draw hard lines
I will not prescribe peptides like BPC-157 for longevity. The regulatory history alone should give patients pause. In September 2023, the FDA placed BPC-157 on its Category 2 list, banning it from compounding pharmacies. In February 2026, RFK Jr.'s FDA partially reversed that decision. Banned, then unbanned, within 28 months. Whatever your politics, that kind of regulatory whiplash is not the foundation for a therapeutic decision. The human safety data for BPC-157 remains essentially nonexistent -- most cited studies are rodent models or in vitro work.
The FDA's own safety alerts page documents the risk trajectory. A Class I recall -- the most serious category, indicating "reasonable probability of serious adverse health consequences" -- hit GenoGenix NAD+ injections for endotoxin contamination. When patients tell me they are getting IV NAD+ at a wellness clinic, I ask what they know about the sourcing. Usually the answer is nothing. That is not informed consent. That is hope with a needle.
I will not prescribe off-label rapamycin for general anti-aging after PEARL. The trial was well-designed and the signal was not there for most patients. I will revisit this if future data changes the picture. That is not stubbornness. That is how evidence-based medicine is supposed to work.
The middle position nobody wants
A 2025 Swiss framework published in Aging and Health Research attempted to define standards for responsible longevity medicine clinics. The fact that such a framework was needed tells you where the field is: growing faster than its evidence base, with enough legitimate science to be taken seriously and enough unregulated commerce to be dangerous.
Here is the position I have landed on, and it satisfies nobody fully.
Patients pursuing $2,000-per-month supplement stacks are running uncontrolled experiments on themselves. The lack of standardized protocols, the variable sourcing, the absence of monitoring -- this is not precision medicine. It is expensive guessing. But physicians dismissing all longevity medicine are ceding the conversation to podcasters and wellness influencers who are happy to fill the vacuum with confident claims and affiliate links.
The middle position means telling a patient: "Your interest in this is not stupid. Some of the science is real. Here is what the evidence actually shows today. Here is what remains unknown. And here is what I need you to do before we talk about rapamycin -- get your colonoscopy, update your lipids, and let me see your DEXA scan."
That conversation takes longer than an eye-roll. It requires staying current on trials I would have dismissed five years ago. It means admitting when a patient's reading has identified data I missed. It is uncomfortable. I do not always get it right.
But I think it is the only honest position available. The interventions with the strongest human evidence for longevity remain stubbornly unsexy: 150 to 300 minutes per week of moderate aerobic activity, resistance training, adequate sleep, a Mediterranean-pattern diet, social connections, not smoking. Decades of data. Nearly free. Routinely ignored by patients who would rather optimize a supplement stack. Those basics come first. Always.
After the basics? Stay curious. Read the trials -- the actual trials, not the podcast summaries. For patients interested in the intersection of artificial intelligence and healthcare, computational tools are accelerating how we identify aging biomarkers and drug targets. But the clinical validation pipeline remains slow by design. That slowness is a feature, not a bug.
The woman with the binder left my office without a rapamycin prescription. She left with a referral for a DEXA scan, an updated lipid panel order, and a printed summary of the PEARL trial. She emailed me two weeks later to say she had read the full paper and appreciated that I had taken her interest seriously rather than dismissing it.
That is the conversation I want to have. Not the one where I am right and the patient is naive. The one where we are both looking at the same evidence and being honest about what it does and does not show. I do not know if rapamycin will ever work for healthy aging. I do not know if semaglutide's epigenetic effects will replicate. I do not know if NMN will matter at scale. Nobody does. The willingness to say that -- out loud, to patients -- is, I think, the beginning of taking longevity medicine seriously.
Frequently Asked Questions
What did the 2025 PEARL trial show about rapamycin for anti-aging?
The PEARL trial, published in Aging in April 2025, was the first large randomized, double-blind, placebo-controlled trial of rapamycin in healthy humans over 48 weeks. It found no significant safety concerns compared to placebo, but also no clear anti-aging signal across the general population. Women on 10mg showed some benefits including increased lean mass and reduced pain, but the data does not support prescribing rapamycin as a broad anti-aging intervention.
Can semaglutide reverse biological aging?
A July 2025 RCT showed that semaglutide reversed several epigenetic aging markers -- PCGrimAge by 3.1 years, PhenoAge by 4.9 years, and DunedinPACE by 0.09 units, all statistically significant. This was the first randomized trial demonstrating a licensed drug reversing epigenetic age. However, epigenetic clocks are surrogate endpoints, not hard clinical outcomes like mortality. The findings need replication before semaglutide can be recommended specifically for anti-aging.
Are NAD+ supplements worth taking for longevity?
The evidence is early but real. A 2024 GeroScience RCT showed NMN improved grip strength, walking speed, and sleep quality in older adults over 12 weeks. A 2025 Nature Metabolism study confirmed NMN and NR raise blood NAD+ levels while plain nicotinamide does not. These are small, short-duration trials. Injectable NAD+ carries additional safety risks -- the FDA issued a Class I recall of GenoGenix NAD+ injections for contamination. Dr. Bari advises patients to complete standard preventive care before investing in supplement protocols.
What does Dr. Sina Bari actually recommend for longevity?
The foundation is always evidence-based preventive care: 150 to 300 minutes of weekly moderate exercise, resistance training, adequate sleep, Mediterranean-pattern diet, social connection, and not smoking. Beyond the basics, I stay current on emerging trial data -- including PEARL and the semaglutide epigenetic findings -- so conversations with patients are grounded in specific evidence rather than blanket dismissals. Every recommendation is anchored in the individual patient's risk profile, labs, and functional status.