Sirtuin-activating compounds (resveratrol, then NMN)

The molecule in a wine glass

In August 2003, a paper in Nature reported that a polyphenol found in red wine and grape skin could extend the lifespan of yeast cells by about 70%. The compound was resveratrol; the mechanism proposed was activation of an enzyme called SIRT1, dubbed by the press a “longevity gene” because its yeast counterpart, Sir2, had already been linked to the life-extending effects of calorie restriction. The paper’s senior author, David Sinclair, was then an assistant professor of pathology at Harvard Medical School, thirty-four years old, with a 1995 PhD in molecular genetics from the University of New South Wales in his native Sydney. Asked by the journal Science about the discovery, Sinclair described resveratrol in the most enthusiastic terms he could find for a compound (per KFF Health News’ 2019 retrospective on that interview). Within a year he had turned the finding into a company; within five years that company would sell for $720 million; within seventeen years he would publish a bestselling book — Lifespan: Why We Age—and Why We Don’t Have To (Atria Books, 10 September 2019) — arguing that aging itself is a treatable disease. Sinclair is now a professor of genetics at Harvard Medical School and the founding director of the Paul F. Glenn Laboratories for the Biological Mechanisms of Aging; the resveratrol story is the discovery that built that platform.

From a $720 million buyout to a bottle on a subscription

Sinclair co-founded Sirtris Pharmaceuticals in 2004 with five colleagues to develop resveratrol and related “sirtuin-activating compounds” into prescription drugs. Sirtris went public in 2007, and on 22 April 2008 GlaxoSmithKline announced it would buy the company for $720 million in cash — $22.50 a share, an 84% premium over Sirtris’s prior closing price — with GSK’s research chief Moncef Slaoui calling the underlying science “potentially transformative.” That first commercial wave ended in 2013, when GSK closed Sirtris’s Cambridge, Massachusetts offices and folded its remaining research into its Philadelphia operations. It did not end Sinclair’s business in longevity. He has since been a founder, investor, equity holder, consultant, or board member of dozens of companies in the field — a February 2019 KFF Health News count put the number at 28, at least 18 of them anti-aging-related — including Elysium Health (which licenses a NAD-booster patent listing Sinclair as an inventor and sells the pills for $60 a bottle), Metro International Biotech (MetroBiotech), which develops a proprietary NMN drug candidate, and Animal Bioscience, a veterinary-supplement company Sinclair founded with his brother Nick Sinclair as CEO. What began as a single laboratory’s academic discovery is now a standing portfolio of consumer and investigational products — an NAD-booster pill sold under an Elysium Health patent license, an NMN drug candidate in MetroBiotech’s development pipeline, and supplements for pets — sold or licensed under Sinclair’s name and credentials, alongside his separate investment in a biological-age testing company.

An activation that was never there

The mechanistic claim behind the entire first commercial wave did not survive scrutiny. In 2010, researchers at Pfizer (Pacholec et al., Journal of Biological Chemistry) reported that resveratrol and the synthetic sirtuin-activating compounds Sirtris had developed, including its lead candidate SRT1720, do not directly activate SIRT1 against native, unlabeled substrates: the activation signal detected in the original screening assay depended on a fluorescent reporter molecule attached to the test peptide, an artifact of the assay rather than a real interaction with the enzyme. The yeast lifespan-extension result itself was a genuine, published finding, but the biochemical mechanism proposed to explain it, and to justify translating it into a human drug, was not.

Sinclair’s public longevity advocacy did not stop; it shifted target, from SIRT1 activation to NAD+ (nicotinamide adenine dinucleotide) restoration. In 2018, his Harvard laboratory reported that treating aged mice with NMN, a NAD+ precursor, restored capillary density and increased treadmill exercise endurance via SIRT1-dependent signaling in blood-vessel cells (Das et al., Cell). It is, again, a real peer-reviewed animal result — and again a surrogate one. A May 2026 evidence review by two Kingston University biologists in The Conversation found that human trials of NMN and the related compound NR reliably raise NAD+-linked blood markers, but that “recent reviews have not found convincing evidence that NMN or NR preserve muscle mass or function in older adults,” and that on outcomes closer to everyday aging — strength, cognition, frailty, measured biological age — “the picture is much less clear.” The same review found human trials have “not shown convincing evidence that resveratrol slows ageing.” No trial of either compound has shown a hard-endpoint benefit — reduced mortality, extended lifespan, or fewer age-related diseases — in humans.

Twenty-eight companies, one aging story

Sinclair’s financial stake in the science he promotes is unusually broad, not concentrated in a single product. The 2019 KFF Health News count of 28 companies documented his position as an inventor on the patent Elysium Health licenses for its NAD-booster pills, and his separate investment in InsideTracker, a biomarker-testing company whose panels he has cited to support his own public claims about his measured biological age. The clearest instance of the conflict shaping the regulatory environment itself involves MetroBiotech: in a letter dated 4 November 2022, the FDA determined that NMN was excluded from the legal definition of a dietary supplement because MetroBiotech held an active Investigational New Drug filing for its own proprietary NMN formulation, MIB-626 — a determination that displaced competing, non-MetroBiotech NMN products from the U.S. supplement market for roughly three years, until trade press reported the FDA reversed the determination in a letter dated September 2025. Sinclair co-founded MetroBiotech; the company’s own drug-development filing was the basis on which competing NMN products were, for a period, excluded from the U.S. supplement market. A 2024 Wall Street Journal investigation reported that companies Sinclair founded have raised more than $1 billion from investors in total, with four having gone bankrupt or largely halted operations and another four not yet having completed human testing of their products.

The trial that failed, the company that closed, the claim that ended a presidency

Three separate, independently documented failures track the case’s two commercial waves. First, the clinical one: a Sirtris-sponsored Phase 2 trial (ClinicalTrials.gov NCT00920556) testing the company’s lead resveratrol formulation, SRT501, in combination with the chemotherapy drug bortezomib for relapsed multiple myeloma, was terminated after 5 of 24 patients receiving SRT501 developed renal failure, with a median time to onset of seven days; two required temporary dialysis. The published trial report (Popat et al., British Journal of Haematology, 2013) concluded the regimen’s safety profile was unacceptable given its minimal efficacy in this patient population. Second, the corporate one: GlaxoSmithKline closed Sirtris’s Cambridge offices in March 2013, five years after paying $720 million for the company, folding its remaining sirtuin research into its Pennsylvania R&D operations.

Third, and most recent: in late February 2024, Animal Bioscience issued a press release quoting Sinclair claiming its dog supplement, Leap Years, was “proven to reverse aging in dogs,” a claim he repeated to his roughly 438,000 followers on X. STAT News reported on 5 March 2024 that no published research had yet demonstrated the compounds in Animal Bioscience’s supplements reversed or slowed aging in dogs at all; the underlying study was an unpublished, non-peer-reviewed preprint. Matt Kaeberlein, a University of Washington longevity researcher and a founding member of the Academy for Health and Lifespan Research — the field’s own professional body, which Sinclair had co-founded and then led as president — resigned his Academy membership over the episode, writing in a 3 March 2024 public statement: “I find it deeply distressing that we’ve gotten to a point where dishonesty in science is normalized to an extent that nobody is shocked when a tenured @Harvard professor falsely proclaims in a press release that a product he is selling to pet owners has ‘reversed aging in dogs’.” Kaeberlein separately described the episode as the textbook case of a scientist selling snake oil. Animal Bioscience revised the press release’s language, and Sinclair resigned as the Academy’s president shortly afterward. The case remains active: resveratrol and NMN are both still sold today as over-the-counter dietary supplements, on the strength of the same category of surrogate, animal-model, and self-reported evidence that has already produced one halted drug trial, one shuttered pharmaceutical company, and one public break with the researcher’s own professional community.