What’s in this post:
The fundamental market advantage of supplement sellers over buyers.
Thesis: The NAD+ debate: is there proof it works in people?
What are sirtuins and NAD+? A plain-English overview.
The two scientists generating the NAD+ hype cycle: how they did it.
Hitting the resveratrol jackpot, and how resveratrol paved the way for NAD+.
Profitable consequences: When research PhDs exaggerate their own science.
There’s a reason you’ve been hearing more about NAD+ shots and supplements lately without feeling like you actually understand what NAD+ is, what it does, how it works, whether it’s worth trying or even why it has become, among celebrities and the so-called “worried well,” such a thing now.
That lack of scientific clarity, I argue below, is partly by design.
When it comes to longevity supplements, ambiguity favors the PhDs selling them for a profit more than the consumers buying them on a prayer.
“In the longevity field…there are individuals who publish high-profile papers, who have a very vested interest in a particular model. And then they publish high-profile reviews where they talk about these things as if they are established fact.”
— Matt Kaeberlein, a prominent sirtuin researcher, April 2024
This post has a simple thesis: NAD+ may eventually be clinically proven to help people age slower and better, but so far there’s zero proof. That lack of evidence hasn’t prevented it from becoming a popular longevity supplement — especially among those on the Hollywood/Instagram axis. At the core of this massive uptick in NAD+ interest are two scientists, at Harvard and MIT, who for years have flooded the zone with research that, coincidentally or not, gave them a clinical basis to sell online sirtuin/NAD+ pills to consumers who may, or may not, receive a benefit.
But first, in case you missed it:
To keep this post as concise as possible, I’ll stay at a non-clinical level of detail to illustrate how talented but ambitious scientists intent on cashing in on their work can use prestigious medical research publications to foster a misleading narrative that provides those scientists lucrative business opportunities.
This isn’t a rare occurrence. In a longevity industry worth an estimated $5.6 trillion1, it’s become a trend.
TREND: A scientist at a prominent lab publishes research suggesting a promising new way to slow or reverse aging. He (they’re almost all men) joins with MBA types to sell an online supplement derived from that research, though the data on humans is inconclusive at best. Other researchers eventually dispute his public claims, but it’s too little, too late! The scientist and his partners, aided by social media influencers, have already developed their unproven product into a lucrative side hustle in the trillion-dollar longevity marketplace.
In plain English: What are sirtuins and NAD+?
Sirtuins are proteins in your cells that act like maintenance workers. They help repair DNA damage and keeping your cellular machinery running smoothly as you age. There are seven different sirtuins in humans (SIRT1 through SIRT7). They also help regulate everything from brain, immune and circadian function to fat metabolism and blood sugar. To function, however, sirtuins need NAD+, a molecule that is present in every cell of your body and is essential for life. (NAD stands for nicotinamide adenine dinucleotide.)
NAD exists in two forms that function as a pair:
NAD+ (the oxidized form) has a positive charge, ready to accept electrons
NADH (a reduced form, where H is hydrogen) is neutral, carrying electrons
These two forms work together in your cells. NAD+ picks up electrons (and hydrogen) during the breakdown of food, becoming NADH, which delivers those electrons to your mitochondria to generate energy and then turns back into NAD+. This cycle occurs constantly, in every cell, thousands of times per second, to keep you alive.
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Will NAD+ therapies be proven to offer positive health impacts on humans? Time will tell. Thus far, there has been no clinical consensus that it does2; some reputable scientists are cautiously optimistic, while others are not. Studies continue to publish on both sides of that clinicial aisle.
We may find out sooner rather than later, however. The day before this post published on AGING with STRENGTH, the journal Nature Aging printed a new NAD+ paper with 28 authors — including two mentioned in this post.3
The graphic below, from that study, provides a helpful overview of NAD+ functions in cells, mice and humans, with references to correlated studies.
(As you read further, keep the above study in mind, because it illustrates a central point about the growing number of conflicts of interest in clinical research that I mention below.)
Sirtuins, discovered in the 1970s, have been in the scientific literature for decades. They became famous in the late 1990s when research first suggested that activating them in yeast could mimic the life-extending effects of calorie restriction — eating less while staying healthy — which had been shown to help various organisms (but not humans, really) live longer.
Here’s the critical twist:
NAD+ may precipitously decline with age4, thereby inhibiting the ability of sirtuins, which rely on NAD+, to help keep cells healthy, well and, just maybe, young.5
NAD+ and the scientist-led hype cycle
But, what if, instead of just losing our NAD+ supply as we age, people could keep topping it off with further supplements and injections, to give our sirtuins all the juice they need to continue repairing and rejuvenating our cells?
Or, in the PT Barnum-like parlance of David Sinclair, a serial dissembler and controversial6 Harvard geneticist who has falsely claimed to have reversed aging in dogs7; suggested a pill may soon reverse aging in humans; and regularly exaggerates his research:
What if human manipulation of NAD+ could slow aging?
In fact, in 2016, Sinclair published a paper on sirtuin/NAD+ with that exact, provocative, and, it turns out, unsupported title: “Slowing ageing (sic) by design: the rise of NAD+ and sirtuin-activating compounds.”8 I say unsupported because the
paper’s abstract ends with this claim: “[A]dvances have demonstrated that it is possible to rationally design molecules that can…possibly extend lifespan in humans.”
There’s no proof yet that NAD+ molecules extend human lifespan. But, as he often has, Sinclair, a media-savvy longevity chiseler, leans on a single word — “possibly” — to keep from being further pilloried by his peers for stretching the truth. Even though Sinclair now has a reputation9 for false claims even within the ranks of Harvard Medical School10, they’ve become a Pavlovian dog whistle to his obedient legion of affiliated and credulous longevity influencers — including Huberman11 and Peter Diamandis12 — and social media followers. Including Elon.
lon·gev·i·ty chis·el·er, n. a person of significant influence who promotes unproven or biased anti-aging nostrums, theories or products for personal gain.
In the NAD+ world, Sinclair is probably, by virtue of his constant habit of spouting falsehoods, one of two of the most prominent scientists who have parlayed sirtuin and NAD+ research into business operations that sell NAD+ supplements — despite no clinical proof that NAD+ slows or reverses human aging.
The other scientist is this sirtuin/NAD+ saga is MIT biology professor Leonard Guarante, a co-founder of Elysium Health, a supplement company that sells $60 bottles of NAD+ supplements — including some that apparently license patents by Sinclair13.
Sinclair and Guarante’s argument for NAD+ supplements appears to be this:
research has shown that overexpressing specific sirtuins that exist in lab yeast, worms, flies and male mice made them live longer
therefore, jacking up sirtuins in people will have the same effect
therefore, giving your sirtuins more NAD+ will extend human life
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Except that there’s no proof it’s true. NAD+ remains a speculative longevity supplement that, in both oral and intravenous forms, is poorly absorbed by the body and causes major discomfort in some people. Yet Guarante, whose peers call him as “Lenny,” continues to hawk oral NAD+.
David, Lenny and resveratrol: a pharmaceutical fleecing
If you’re not yet willing to question Sinclair and Guarante’s aggressive marketing of NAD+ as an anti-aging supplement, perhaps their earlier, spectacular foray into resveratrol, a polyphenol found in plants and red wine that Sinclair spent years falsely boosting as a longevity drug, will get you to reconsider.
Hitting the resveratrol jackpot
Sinclair and Guarante are old colleagues. As a postdoctoral researcher in the late 1990s, Sinclair worked on sirtuin-related aging research in Guarante’s MIT lab before moving to Harvard. Not long after that, in 2007, Guarante joined Sirtris Pharmaceuticals (SIRT…get it?), co-founded by Sinclair to work on resveratrol supplements.
The following year, Sirtris was acquired by GlaxoSmithKline for an astounding figure: $720 million. How Sinclair and Guarante managed to hoodwink global pharma executives into believing resveratrol was worth that much money is not clear.
Needless to say, within two years of the sale, GSK had closed down its work on resveratrol, and, four years after that, it shuttered Sirtris permanently.
Goodbye, resveratrol; hello, NAD+
By then, Guarante and Sinclair, their fortunes presumably made, had already turned to sirtuins and NAD+ as a potential breakthrough longevity compound. In 2014, Guarante and two venture capital executives founded Elysium Health.
The following year, Sinclair co-founded his own company, Metro International Biotech, to develop its own version of an NAD+ precursor called NMN (nicotinamide mononucleotide), putting him in potential competition with Gaurante and Elysium.
In 2016, Sinclair published his “Slowing ageing by design” NAD+ research paper. Soon enough, he began referring to sirtuins as “longevity genes,” earning Sinclair a fresh rounds of calumny from other scientists, more of whom were tiring of what can only be described as his exhausting penchant for bullshit.14
Scientists shouldn’t overstate their research
There’s nothing wrong with scientists making a fortune selling a company to a breathtakingly naive global pharmaceutical conglomerate. There’s nothing criminal about writing a book — as Sinclair did — stating that aging is optional. Hundreds of doctors, biologists, geneticists and other scientists become entrepreneurs and authors.
Not all that many, however, have leaned as far — or perhaps as profitably — over the cliff of verifiable, proven science to sell longevity nostrums in a frothy market to everyday consumers as have Sinclair and Guarante, aided by MBA-armored business partners.
Despite their clinical rivalries and past clashes, Sinclair and Guarante remain tightly professionally. bound. In 2017, they co-founded Galilei Biosciences, a venture-backed company with no public website that is developing compounds to activate the SIRT6 sirtuin protein, which has shown some promise in extending lifespan — in male mice.
Guarante claims and exaggerations
In a big Wall Street Journal profile of him this past March, Guarante claims that sirtuins slow down aging in humans and that bottles of Elysium’s NAD+ supplement will activate those age-slowing proteins.15
At risk of being repetitive: There’s no clinical proof that that is true.
On his Elysium Health bio page, Gaurante also claims that he “was the first to identify SIR2” — a sirtuin — “as the gene that controls aging in yeast cells.” Maybe not.16 The paper that first made that discovery had three authors, the first of whom is Matt Kaeberlein, who was then a postdoc in Gaurante’s lab. Guarante, the lab director who supervised the research, was listed third. Could his students have made this discovery without him? Maybe not. Is Guarante legitimately “the first” person to show sirtuins made yeast live longer? Not likely.
Sinclairian b.s.
Sinclair seems especially eager to have his name go down in longevity history.
In 2019, he wrote a book, “Lifespan,” with an ostentatious subtitle: “Why We Age and Why We Don’t Have To.” If science were a religion, Sinclair would be a snake-handling preacher speaking in tongues.
In his tweet that caught Elon Musk’s attention, Sinclair mentioned the “potential to reverse aging with a single pill.” On Huberman’s podcast in 2021, Sinclair said he wanted to democratize access to biological age tests17, and that he’d developed one on DoctorSinclair.com. Maybe that was true in 2021. But since at least 2024, DoctorSinclair.com is just a pass-through url for TallyHealth, a longevity supplements company co-founded by you-know-who.
What kind of scientist does that?
“There’s plenty of things he’s said that aren’t true.”
— longevity biologist Matt Kaeberlein, referring to David Sinclair
Perhaps the kind of scientist who wants to be taken seriously as a world-class researcher while also holding stakes in about 20 profit-focused biotech startups18.
Speaking of which: Remember that new NAD+ research paper I asked you to keep in mind near the top of this post?
Check out the paper’s 500-word ethics declaration, in which the 28 authors voluntarily declare any outside business interests that could present a conflict with their research. Almost half of that lengthy declaration is taken up by just one contributing researcher — David Sinclair, surprise! — and the 16 separate bio-longevity companies (and 2 venture capital firms) he’s involved with (see image below).
(Notably, of the 12 other authors who list outside business affiliations, more than half are associated with or also paid by Chromadex, a company that makes — not surprise! — the NAD+ precursor NR aka nicotinamide riboside. Chromadex is a direct competitor to Elysium Health.)
An incongruent lack of proof
In response to their critics, Sinclair and Guarante have issued no shortage of ripostes, excuses or, for Watergate aficionados, non-denial denials. After he was caught prevaricating about reversing aging in dogs, Sinclair blamed a marketing vendor for misquoting him but was still forced to resign as president of the Academy for Health and Lifespan Research.
In his profile by the WSJ, Gaurante defended the lack of proof for NAD+ efficacy in humans by saying research is “moving in the direction where there will be stronger and stronger data, maybe not in everything, but in some significant human health areas in the future.”
A careful if supremely defensible assertion — but one incongruent with selling NAD+ as an anti-aging supplement. And that’s the problem.
https://www.forbes.com/sites/sindhyavalloppillil/2025/07/29/why-vc-backed-longevity-startups-are-dying-in-a-5-trillion-wellness-market/
https://www.cell.com/cell-metabolism/fulltext/S1550-4131(25)00212-8
https://www.nature.com/articles/s43587-025-00947-6
Or, according to this 2022 paper, it may not: https://www.mdpi.com/2072-6643/14/1/101
As an example of how the reams of sirtuin and NAD+ research has confounded consumer-facing AI applications, I asked two leading consumer AI apps — Claude.ai (Opus 4.1) and Google’s Gemini (Flash 2.5) — the following question:
“Is it fact or theory that 1. NAD+ declines in humans as they age, and 2. that NAD+ decline inhibits sirtuins’ ability to help keep cells healthy and well”
Claude replied: 1 is fact; and 2 is theory.
Gemini replied: 1 is theory (but widely supported); and 2 is fact.
Expert humans also have differing opinions. Matt Kaeberlein, a University of Washington biologist who was the lead author on a seminal 1999 paper that showed sirtuins extended lifespan in yeast, said in a lengthy podcast discussion last year that he wasn’t convinced NAD+ declines with age. (See 1:34:37 of the transcript). In a August 2025 podcast, Peter Attia and Eric Verdin, the CEO of the Buck Institute for Research on Aging, in Novato, Calif., agreed that NAD+ declines greatly with age.
https://www.wsj.com/health/wellness/david-sinclair-longevity-aging-criticism-645fddc5?mod=article_inline
https://www.statnews.com/2024/03/05/david-sinclair-harvard-longevity-scientist-reversing-aging-dogs/
https://www.nature.com/articles/nrm.2016.93
https://pmc.ncbi.nlm.nih.gov/articles/PMC9669175/
https://x.com/jflier/status/1495833104510038026
https://www.hubermanlab.com/episode/dr-david-sinclair-the-biology-of-slowing-and-reversing-aging
www.youtube.com/watch?v=1l3lGy07Fgo&t=40s
https://kffhealthnews.org/news/a-fountain-of-youth-pill-sure-if-youre-a-mouse/
A thorough takedown of Sinclair’s work on sirtuins: https://www.science.org/content/blog-post/speaking-illusions-sirtuins-and-longevity
https://www.wsj.com/health/wellness/longevity-antiaging-leonard-guarente-business-f55643f4?mod=health_lead_story
This is a cautionary AI tale: AI searches tend to give sole credit to Guarante for this discovery — likely because the information source that AI searches is the public internet. That often favors whoever is asserting something loudest and proudest, so to speak. Thus, Guarante’s discovery claim on Elysium’s website, without any other sources contesting it, makes it ispo facto a fact, according to AI.
youtu.be/n9IxomBusuw?si=Pfg6NtWZTFsBZkr1&t=7540
https://sinclair.hms.harvard.edu/david-sinclairs-affiliations
Oh boy, I could not agree more. I have followed Sinclair's for many years and have never found his claims to be supported by science. At one point, all the men I knew of a certain age seemed to be taking his NMN/metformin/resveratrol cocktail. Lately I am getting so many questions about NAD+ injectibles that I have been meaning to write about it. Now, thanks to you, I don't have to!
Paul, I really appreciate your investigative reporting and detailed explanations. They’re very helpful for me and for my patients. This brought me back to the late 90s when we did research on the effects of resveratrol supplementation and endothelial function in human beings and found a big fat goose egg. Keep up the great work.