David A. Sinclair Explained

David A. Sinclair
Birth Date:26 June 1969
Birth Place:Sydney, New South Wales, Australia
Fields:Molecular genetics
Workplaces:Harvard Medical School
Alma Mater:University of New South Wales (BSc, PhD)
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Doctoral Advisor:Ian Dawes
Academic Advisors:Leonard Guarente
Known For:Research on aging
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David Andrew Sinclair (born June 26, 1969)[1] [2] is an Australian-American biologist and academic known for his research and controversial claims on aging and epigenetics. Sinclair is a professor of genetics at Harvard Medical School.

Early life and education

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.[2] 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.[3] [2] [4]

Career

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.

In 1999, after four years of working as a postdoctoral researcher for Guarente, Sinclair was hired at Harvard Medical School.[2] In 2003, his lab was small and struggling for funding.[2] 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.[2]

In 2004, Sinclair, along with Andrew Perlman, Christoph Westphal, Richard Aldrich, Richard Pops, and Paul Schimmel, founded Sirtris Pharmaceuticals.[5] [6] Sirtris was focused on developing Sinclair's research into activators of sirtuins, work that began in the Guarente lab.[5] 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."[5] 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.[5] [7] The company's initial product was called SRT501, and was a formulation of resveratrol.[8] 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.[9] [10] Despite the clinical failures of resveratrol[11] and its scientific debunking,[12] Sinclair continues to endorse taking resveratrol.[13]

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;[14] Sinclair was a co-founder.[15] Genocea laid off most of its workforce in 2022 after presenting disappointing data at AACR.[16]

In 2008, Sinclair was promoted to tenured professor at Harvard Medical School. A few years later, he also became a conjoint professor at the School of Medical Sciences at the University of New South Wales.[17]

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.[18]

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.[19] [20] Tilly's work was controversial, with some groups unable to replicate it.[21] [22] The company came under pressure for skirting US regulatory authorities for fertility testing.[23]

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. CohBar has responded to an SEC order to delist the company based on a NASDAQ finding that the company is a public shell.[24]

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.[26]

In September 2019, Sinclair published co-written with journalist Matthew LaPlante and translated into 18 languages.[27] This was also released as an audiobook on Audible and read by Sinclair.[28] 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.[29] 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.[30]

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.[31] Sinclair claims that improving his nutrition and exercise routine has shaved almost a decade off his biological age.[32]

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. This claim met with widely expressed outrage in the research community.[33] The controversy resulted in a wave of resignations from The Academy for Health and Lifespan Research, a group of scientists that Sinclair had co-founded, and Sinclair resigned as the Academy's President in March 2024.[34]

Research

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.[35]

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.[2] In 2002, after he had left for Harvard, he clashed with Guarente at a scientific meeting at Cold Spring Harbor Laboratory, challenging Guarante's description of how sir2 might be involved in aging; this set off a scientific rivalry.[5]

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.[2] This led to publications authored in part by Sinclair in both Nature and Science in 2003.[5] 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 Despite the scientific debunking of resveratrol, Sinclair maintains an outspoken advocacy for resveratrol as an anti-aging drug and supplement.[2] [5] [36] High-profile papers claiming age reversal of mice have also come under intense scrutiny.[37] Sinclair's lab has continued to work on resveratrol and analogues of it as part of their research program in anti-aging.[36]

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.[38] 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.[39] 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.[40]

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.[41] [42] 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.[43] Sinclair's claims of reverse aging are controversial and received criticism from other scientists including Charles Brenner,[44] [45] Peter Attia,[46] and Matt Kaeberlein. Sinclair's claims have been questioned in the popular press.

Selected publications

Notes and References

  1. Web site: Sinclair . David . 2023-06-28 . David A Sinclair . 2023-06-28 . Twitter . en.
  2. News: Duncan . David Ewing . August 15, 2007 . The Enthusiast . live . https://web.archive.org/web/20200430213928/https://www.technologyreview.com/2007/08/15/224308/the-enthusiast/ . April 30, 2020 . August 17, 2017 . MIT Technology Review . en.
  3. Web site: David Sinclair . 17 August 2017 . The Sinclair Lab, Harvard Medical School, Department of Genetics . 17 August 2017 . https://web.archive.org/web/20170817081324/http://genetics.med.harvard.edu/sinclair/people/sinclair.php . live .
  4. https://www.eurekalert.org/news-releases/664233 Molecules discovered that extend life in yeast, human cells
  5. Couzin . J . 27 February 2004 . Scientific community. Aging research's family feud. . Science . 303 . 5662 . 1276–9 . 10.1126/science.303.5662.1276 . 14988530 . 161459205 . 17 August 2017 . 17 August 2017 . https://web.archive.org/web/20170817080718/http://science.sciencemag.org/content/303/5662/1276.full?ijkey=boCCM4akb2Rj6&keytype=ref&siteid=sci . live .
  6. Web site: March 1, 2007 . Sirtris S-1 Registration for IPO . Sirtris via SEC Edgar . August 17, 2017 . February 13, 2017 . https://web.archive.org/web/20170213165600/https://www.sec.gov/Archives/edgar/data/1388775/000104746907001505/a2176355zs-1.htm . live .
  7. News: Wade . Nicholas . 17 August 2009 . Tests Begin on Drugs That May Slow Aging . The New York Times . 17 August 2017 . 17 August 2017 . https://web.archive.org/web/20170817121838/http://www.nytimes.com/2009/08/18/science/18aging.html?8dpc . live .
  8. News: McBride . Ryan . 12 August 2010 . Former Sirtris Execs' Nonprofit Starts Selling Resveratrol with Potential Anti-Aging Effects Online . Xconomy . 17 August 2017 . 27 March 2019 . https://web.archive.org/web/20190327103618/https://xconomy.com/boston/2010/08/12/former-sirtris-execs-nonprofit-starts-selling-resveratrol-with-potential-anti-aging-effects-online/?single_page=true . live .
  9. News: Carroll . John . McBride . Ryan . Mar 12, 2013 . Updated: GSK moves to shutter Sirtris' Cambridge office, integrate R&D . en . FierceBiotech . August 17, 2017 . April 28, 2019 . https://web.archive.org/web/20190428120955/https://www.fiercebiotech.com/r-d/updated-gsk-moves-to-shutter-sirtris-cambridge-office-integrate-r-d . live .
  10. Web site: GSK absorbs controversial 'longevity' company: News blog . Nature Blog . 2017-08-17 . 2013-12-17 . https://web.archive.org/web/20131217235120/http://blogs.nature.com/news/2013/03/gsk-absorbs-controversial-longevity-company.html . live . .
  11. Web site: 2014-05-12 . Debunked: Red Wine Antioxidant Won't Help You Live Longer . 2024-05-03 . NBC News . en.
  12. Kaeberlein . Matt . McDonagh . Thomas . Heltweg . Birgit . Hixon . Jeffrey . Westman . Eric A. . Caldwell . Seth D. . Napper . Andrew . Curtis . Rory . DiStefano . Peter S. . Fields . Stanley . Bedalov . Antonio . Kennedy . Brian K. . 2005-04-29 . Substrate-specific activation of sirtuins by resveratrol . The Journal of Biological Chemistry . 280 . 17 . 17038–17045 . 10.1074/jbc.M500655200 . free . 0021-9258 . 15684413.
  13. Web site: How a Harvard genetics professor reversed his biological age in 3 steps . 2024-05-03 . Fortune Well . en.
  14. News: Richtel . Matt . 16 May 2007 . Warding Off Diseases, Many Vaccines at a Time . The New York Times . 26 August 2017 . 17 August 2017 . https://web.archive.org/web/20170817082908/http://www.nytimes.com/2007/05/16/business/smallbusiness/16genocea.html?mcubz=0 . live .
  15. News: McBride . Ryan . May 1, 2008 . Polaris' Bitterman is humble about his early VC success . Boston Business Journal . August 17, 2017 . August 17, 2017 . https://web.archive.org/web/20170817081458/https://www.bizjournals.com/boston/blog/mass-high-tech/2008/05/polaris-bitterman-is-humble-about-his-early.html . live .
  16. News: Five years into neoantigen work, cash-strapped Genocea lays off staff as it looks for 'strategic alternatives'. August 14, 2022. .
  17. Web site: Professor David Sinclair School of Medical Sciences . 2017-11-26 . medicalsciences.med.unsw.edu.au . 2017-12-01 . https://web.archive.org/web/20171201035521/https://medicalsciences.med.unsw.edu.au/people/professor-david-sinclair . live .
  18. News: Goldstein . Jacob . 26 December 2008 . Harvard Researcher Tied to Shaklee 'Anti-Aging Tonic' Vivix . WSJ . 27 November 2017 . 1 December 2017 . https://web.archive.org/web/20171201041834/https://blogs.wsj.com/health/2008/12/26/harvard-researcher-tied-to-shaklee-anti-aging-tonic-vivix/ . live .
  19. Web site: August 29, 2012 . OvaScience S-1 . OvaScience via SEC Edgar . August 17, 2017 . May 14, 2017 . https://web.archive.org/web/20170514000041/https://www.sec.gov/Archives/edgar/data/1544227/000104746912008575/a2210793zs-1.htm . live .
  20. News: Weintraub . Karen . December 9, 2016 . Can fertility startup OvaScience really help women conceive late in life, as promised? . en . MIT Technology Review . August 17, 2017 . February 14, 2017 . https://web.archive.org/web/20170214002826/https://www.technologyreview.com/s/603065/rejuvenating-the-chance-of-motherhood/ . live .
  21. Grieve . Kelsey M. . McLaughlin . Marie . Dunlop . Cheryl E. . Telfer . Evelyn E. . Evelyn Telfer . Anderson . Richard A. . 2015 . The controversial existence and functional potential of oogonial stem cells . Maturitas . 82 . 3 . 278–281 . 10.1016/j.maturitas.2015.07.017 . 26278874 . free.
  22. Powell . K . 15 June 2006 . Born or made? Debate on mouse eggs reignites. . Nature . 441 . 7095 . 795 . 10.1038/441795a . 16778853 . 2006Natur.441..795P . 3111297. free .
  23. News: Turmoil at Troubled Fertility Company Ovascience. .
  24. Web site: 2023-11-27 . CohBar, Inc.: Notice of Delisting or Failure to Satisfy a Continued Listing Rule or Standard; Transfer of Listing (Form 8-K) . 2024-05-22 . CohBar, Inc. . en.
  25. News: Grant . Bob . May 1, 2015 . Follow the Funding . The Scientist . January 8, 2022 . April 11, 2018 . https://web.archive.org/web/20180411122800/https://www.the-scientist.com/?articles.view%2FarticleNo%2F42799%2Ftitle%2FFollow-the-Funding%2F . live .
  26. Web site: Grantome . January 22, 2021 . January 28, 2021 . https://web.archive.org/web/20210128230722/https://grantome.com/search?q=@author%20%20David%20Sinclair . live .
  27. Finkel . Toren . 2019-09-10 . The enlightenment of age . Nature . en . 573 . 7773 . 193–194 . 10.1038/d41586-019-02667-5 . 2019Natur.573..193F . free.
  28. Book: Sinclair, David A . Lifespan: Why We Age - and Why We Don't Have To . 10 September 2019 . Audible . 22 February 2020 . 22 February 2020 . https://web.archive.org/web/20200222055051/https://www.audible.com.au/pd/Lifespan-Audiobook/000829237X . live .
  29. Web site: 2022-05-10 . The Anti-Aging Supplements David Sinclair Takes Skeptical Review . 2022-11-16 . NOVOS . en-US.
  30. News: In NAC Docket, NAD+ Drug Firm Suggests US FDA Get Serious About Dietary Ingredient Regulations . 2023-01-07 . en.
  31. Web site: Tally Health — Welcome to a New Age. . 2023-03-28 . Tally Health . en-US.
  32. News: Medaris . Anna . A 53-year-old longevity researcher says his 'biological age' is a decade younger thanks to 4 daily habits — but the science behind them is mixed . 28 March 2023 . Insider.
  33. Web site: Molteni . Megan . 2024-03-05 . Harvard longevity scientist sparks furor with claim about reversing aging in dogs . 2024-03-26 . STAT . en-US.
  34. News: Marcus . Alex Janin, Dominique Mosbergen and Amy Dockser . Star Scientist's Claim of 'Reverse Aging' Draws Hail of Criticism . 2024-04-29 . WSJ . en-US.
  35. Web site: How scientists want to make you young again.
  36. News: Wallace . Benjamin . An MIT Scientist Claims That This Pill Is the Fountain of Youth . en . . 2017-08-17 . 2017-08-14 . https://web.archive.org/web/20170814204010/http://nymag.com/scienceofus/2016/08/is-elysium-healths-basis-the-fountain-of-youth.html . live .
  37. Gomes . Ana P. . Price . Nathan L. . Ling . Alvin J. Y. . Moslehi . Javid J. . Montgomery . Magdalene K. . Rajman . Luis . White . James P. . Teodoro . João S. . Wrann . Christiane D. . Hubbard . Basil P. . Mercken . Evi M. . 2013-12-19 . PUBPEER Dissection of Anomalies with Figures in Declining NAD(+) induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging . PubPeer . en . 2020-11-24 . 2021-03-02 . https://web.archive.org/web/20210302140926/https://pubpeer.com/publications/A367937A1FE47F62833BCA961CA087 . live .
  38. Lu . Yuancheng . Brommer . Benedikt . Tian . Xiao . Krishnan . Anitha . Meer . Margarita . Wang . Chen . Vera . Daniel L. . Zeng . Qiurui . Yu . Doudou . Bonkowski . Michael S. . Yang . Jae-Hyun . Zhou . Songlin . Hoffmann . Emma M. . Karg . Margarete M. . Schultz . Michael B. . 2020-12-03 . Reprogramming to recover youthful epigenetic information and restore vision . Nature . en . 588 . 7836 . 124–129 . 10.1038/s41586-020-2975-4 . 0028-0836 . 7752134 . 33268865. 2020Natur.588..124L .
  39. Web site: 2023-04-23 . Life Biosciences Presents Groundbreaking Data at ARVO Demonstrating Restoration of Visual Function in Nonhuman Primates . 2024-05-21 . Yahoo Finance . en-US.
  40. Web site: Epigenetic reprogramming- A novel gene therapy that restores vision loss in a nonhuman primate model of NAION . 2024-05-21 . iovs.arvojournals.org.
  41. Yang . Jae-Hyun . Hayano . Motoshi . Griffin . Patrick T. . Amorim . João A. . Bonkowski . Michael S. . Apostolides . John K. . Salfati . Elias L. . Blanchette . Marco . Munding . Elizabeth M. . Bhakta . Mital . Chew . Yap Ching . Guo . Wei . Yang . Xiaojing . Maybury-Lewis . Sun . Tian . Xiao . 2023-01-12 . Loss of epigenetic information as a cause of mammalian aging . Cell . en . 186 . 2 . 305–326.e27 . 10.1016/j.cell.2022.12.027 . 10166133 . 36638792.
  42. Web site: Scientists Have Reached a Key Milestone in Learning How to Reverse Aging . 2023-01-13 . Alice . Park . www.yahoo.com . en-US.
  43. Timmons . James A. . Brenner . Charles . 2024-02-29 . The information theory of aging has not been tested . Cell . en . 187 . 5 . 1101–1102 . 10.1016/j.cell.2024.01.013. 38428390 .
  44. Web site: 2023-07-14 . "We won't get eternal life. Scientists who promise it are just selling BS" . 2023-08-21 . ctech . en.
  45. Brenner . Charles . 2023-01-01 . A science-based review of the world's best-selling book on aging . Archives of Gerontology and Geriatrics . 104 . 104825 . 10.1016/j.archger.2022.104825 . 0167-4943 . 9669175 . 36183524.
  46. Web site: LaMotte . Sandee . 2023-02-10 . Restrict calories to live longer, study says, but critics say more proof is needed . 2023-08-21 . CNN . en.

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