David A. Sinclair

David Andrew Sinclair was born in Australia in 1969 and grew up in St Ives, New South Wales. His paternal grandmother had emigrated to Australia following the suppression of the Hungarian Uprising of 1956, and his father changed the family name from Szigeti to Sinclair.^[3] Sinclair studied at the University of New South Wales, Sydney, obtaining a BSc in biochemistry with honours in 1991 and a Ph.D. in molecular genetics in 1995, focusing on gene regulation in yeast. He also won the Australian Commonwealth Prize.^[1][3][5]

In 1993, he met Leonard P. Guarente, a Massachusetts Institute of Technology professor who studied yeast as a model of aging, when Guarente was on a lecture tour in Australia, and the meeting spurred Sinclair to apply for a post-doc position in Guarente's lab.^[3]

In 1999, after four years of working as a postdoctoral researcher for Guarente, Sinclair was hired at Harvard Medical School.^[3] In 2003, his lab was small and struggling for funding.^[3] In 2004, Sinclair met with the philanthropist Paul F. Glenn who donated $5 million to Harvard to establish the Paul F. Glenn Laboratories for the Biological Mechanisms of Aging at Harvard, of which Sinclair became the founding director. He is no longer a director of this center.^[3]

In 2004, Sinclair, along with Andrew Perlman, Christoph Westphal, Richard Aldrich, Richard Pops, and Paul Schimmel, founded Sirtris Pharmaceuticals.^[6][7] Sirtris was focused on developing Sinclair's research into activators of sirtuins, work that began in the Guarente lab.^[6] The company was specifically focused on resveratrol formulations and derivatives as activators of the SIRT1 enzyme; Sinclair became known for making statements about resveratrol like: "(It's) as close to a miraculous molecule as you can find. ... One hundred years from now, people may be taking these molecules on a daily basis to prevent heart disease, stroke, and cancer."^[6] Most of the anti-aging field was more cautious, especially with regard to what else resveratrol might do in the body and its lack of bioavailability.^[6][8] The company's initial product was called SRT501, and was a formulation of resveratrol.^[9] Sirtris went public in 2007 and was subsequently purchased by and made a subsidiary of GlaxoSmithKline in 2008 for $720 million. Five years later, GSK shuttered the Sirtris program without successful drug development.^[10][11] Despite the clinical failures of resveratrol^[12] and its scientific debunking,^[13] Sinclair continues to endorse taking resveratrol.^[14]

In 2006, Genocea Biosciences was founded based on the work of Harvard scientist Darren E. Higgins around antigens that stimulate T cells and the use of these antigens to create vaccines;^[15] Sinclair was a co-founder.^[16] Genocea laid off most of its workforce in 2022 after presenting disappointing data at AACR.^[17]

In 2008, Sinclair was promoted to tenured professor at Harvard Medical School.^[18] A few years later, he also became a conjoint professor at the School of Medical Sciences at the University of New South Wales.^[18]

In 2008, Sinclair joined the scientific advisory board of Shaklee and helped them devise and introduce a product containing resveratrol called "Vivix". After the Wall Street Journal requested an interview about his work with the company and its marketing, he disputed the use of his name and words to promote the supplement, and resigned.^[19]

In 2011, Sinclair was a co-founder of OvaScience with Michelle Dipp (who had been involved with Sirtris), Aldrich, Westphal, and Jonathan Tilly, based on scientific work done by Tilly concerning mammalian oogonial stem cells and work on mitochondria by Sinclair.^[20][21] Tilly's work was controversial, with some groups unable to replicate it.^[22][23] The company came under pressure for skirting US regulatory authorities for fertility testing.^[24]

In 2011, Sinclair was also a co-founder of CohBar, along with Nir Barzilai and other colleagues. CohBar aimed to discover and develop novel peptides derived from mitochondria.^[25] CohBar has responded to an SEC order to delist the company based on a NASDAQ finding that the company is a public shell.^[26]

In 2015, Sinclair described to The Scientist his efforts to get funding for his lab, how his lab grew to around 20 people, shrank back down to about 5, and then grew again as he brought in funding from philanthropic organizations and companies, including companies that he helped to start.^[25] In 2015, his lab had 22 people and was supported by one R01 grant and was 75% funded by non-federal funds.^[25] However, as of 2016, this was no longer true as his federal funding began to increase.^[27]

In November 2022, Sinclair's company Metro Biotech successfully urged the FDA to take actions to take NMN off the market as a supplement because Metro Biotech had registered NMN in investigational new drug applications.^[28]

In 2023, Sinclair co-founded Tally Health, a supplement company with a stated goal is to "change the way we age" at the cellular level.^[29] Sinclair claims that improving his nutrition and exercise routine has shaved almost a decade off his biological age.^[30]

In 2024, Sinclair and his brother Nicholas Sinclair announced that their company Animal Bioscience had "proven" that a supplement for dogs with nondisclosed ingredients reversed aging. The claim met with criticism and skepticism from other longevity researchers.^[31][32] It resulted in what The Wall Street Journal described as a "cascade" of resignations from outraged members of The Academy for Health and Lifespan Research, a group of scientists that Sinclair had co-founded.^[32] Sinclair resigned as the Academy's President in March 2024.^[32]

Sinclair has expressed the view that there is no limit to human lifespan, and that there is a backup copy of the genetic and epigenetic information in us.^[33]

While Sinclair was in Guarente's lab, he discovered that sirtuin 1 (called sir2 in yeast) slows aging in yeast by reducing the accumulation of extrachromosomal rDNA circles. Others working in the lab at the time identified NAD as an essential cofactor for sirtuin function.^[3] In 2002, after he had left for Harvard, he clashed with Guarente at a scientific meeting at Cold Spring Harbor Laboratory, challenging Guarente's description of how sir2 might be involved in aging; this set off a scientific rivalry.^[6]

In 2003, Sinclair learned that scientists at a Pennsylvania biotech company called Biomol Research Laboratories had developed a biochemical assays in which they thought that polyphenols including resveratrol activated SIR2.^[3] This led to publications authored in part by Sinclair in both Nature and Science in 2003.^[6] However, by 2005, it became clear that the biochemical assay consists of a fluorescent probe that interacts nonspecifically with resveratrol and that resveratrol is not a SIR2 activator^[13] Despite the scientific debunking of resveratrol, Sinclair maintains an outspoken advocacy for resveratrol as an anti-aging drug and supplement.^[3][6][34] High-profile papers claiming age reversal of mice have also come under intense scrutiny.^[35] Sinclair's lab has continued to work on resveratrol and analogues of it as part of their research program in anti-aging.^[34]

In December, 2020, Sinclair's group published that three Yamanaka transcription factors, Oct4, Sox2, and Klf4, when delivered together in a virus, could safely reverse the age of human and mouse cells, and restore the vision of old mice and mice with glaucoma.^[36] In 2023, with Bruce Ksander's lab at Mass Eye and Ear, they presented a poster at the annual ARVO conference accompanied by a company press release claiming that vision could be restored in non-human primates.^[37] In fact, the research remains unpublished but the poster abstract does not address the vision of the twelve Oct4-Sox2-Klf4-treated African green monkeys.^[38]

In January 2023, Sinclair's lab published research in Cell purporting to support his Information Theory of Aging, the idea that mammalian aging is due to the loss of epigenetic information, and that Yamanaka factors could exert a degree of artificial control over senescence and rejuvenation in mice.^[39][40] The paper earned a formal reply pointing out that the treatment used in the paper is known to produce p53-dependent cell death in a 30-day period in which the mice were not observed.^[41] Sinclair's claims of reverse aging are controversial and received criticism from other scientists including Charles Brenner,^[42][43] Peter Attia,^[44] and Matt Kaeberlein.^[31] Sinclair's claims have been questioned in the popular press.^[31][32]

In September 2019, Sinclair published Lifespan: Why We Age – and Why We Don't Have To co-written with journalist Matthew LaPlante and translated into 18 languages.^[45] This was also released as an audiobook on Audible and read by Sinclair.^[46] Sinclair broadly discusses his longevity practices on social media and includes them in his book. They include daily doses of nicotinamide mononucleotide (NMN) and resveratrol, which Sinclair claims are activators of SIRT1.^[47]

• 2023, The Information Theory of Aging, Nature Aging
• 2023, Chemically induced reprogramming to reverse cellular aging, Aging
• 2023, Loss of epigenetic information as a cause of mammalian aging, Cell
• 2021, The economic value of targeting aging, Nature Aging
• 2020, Reprogramming to recover youthful epigenetic information and restore vision, Nature
• 2008, [https://pubmed.ncbi.nlm.nih.gov/19041753/ SIRT1 redistribution on chromatin promotes genomic stability but alters gene expression during aging, Cell