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. Sinclair studied at the University of New South Wales, Sydney, obtaining a bachelor of science in biochemistry in 1991 and a Ph.D. in molecular genetics in 1995, focusing on gene regulation in yeast. He also won the Australian Commonwealth Prize.{{Cite web |title=David Sinclair |url=https://genetics.med.harvard.edu/sinclair/people/sinclair.php |access-date=17 August 2017 |publisher=The Sinclair Lab, Harvard Medical School, Department of Genetics |archive-date=17 August 2017 |archive-url=https://web.archive.org/web/20170817081324/http://genetics.med.harvard.edu/sinclair/people/sinclair.php |url-status=live }}[https://www.eurekalert.org/news-releases/664233 Molecules discovered that extend life in yeast, human cells]

Sinclair met Massachusetts Institute of Technology professor Leonard P. Guarente in 1993. Guarente had studied yeast as a model of aging, and after meeting him Sinclair, interviewed for a post-doc position in Guarente's lab.

He worked as a postdoctoral researcher for Guarente for four years and in 1999 he was hired at Harvard Medical School. 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. In 2004, Sinclair founded Sirtris Pharmaceuticals along with Andrew Perlman, Christoph Westphal, Richard Aldrich, Richard Pops, and Paul Schimmel.{{Cite journal |last=Couzin |first=J |date=27 February 2004 |title=Scientific community. Aging research's family feud. |url=https://www.science.org/doi/full/10.1126/science.303.5662.1276?siteid=sci&keytype=ref&ijkey=boCCM4akb2Rj6 |journal=Science |volume=303 |issue=5662 |pages=1276–9 |doi=10.1126/science.303.5662.1276 |pmid=14988530 |s2cid=161459205 |access-date=17 August 2017 |archive-date=17 August 2017 |archive-url=https://web.archive.org/web/20170817080718/http://science.sciencemag.org/content/303/5662/1276.full?ijkey=boCCM4akb2Rj6&keytype=ref&siteid=sci |url-status=live }}{{Cite web |date=March 1, 2007 |title=Sirtris S-1 Registration for IPO |url=https://www.sec.gov/Archives/edgar/data/1388775/000104746907001505/a2176355zs-1.htm |publisher=Sirtris via SEC Edgar |access-date=August 17, 2017 |archive-date=February 13, 2017 |archive-url=https://web.archive.org/web/20170213165600/https://www.sec.gov/Archives/edgar/data/1388775/000104746907001505/a2176355zs-1.htm |url-status=live }}

Sirtris was focused on developing Sinclair's research into activators of sirtuins, work that began in the Guarente lab. 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." 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.{{Cite news |last=Wade |first=Nicholas |date=17 August 2009 |title=Tests Begin on Drugs That May Slow Aging |work=The New York Times |url=https://www.nytimes.com/2009/08/18/science/18aging.html?8dpc |access-date=17 August 2017 |archive-date=17 August 2017 |archive-url=https://web.archive.org/web/20170817121838/http://www.nytimes.com/2009/08/18/science/18aging.html?8dpc |url-status=live }} The company 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.{{Cite news |last1=Carroll |first1=John |last2=McBride |first2=Ryan |date=Mar 12, 2013 |title=Updated: GSK moves to shutter Sirtris' Cambridge office, integrate R&D |language=en |work=FierceBiotech |url=http://www.fiercebiotech.com/r-d/updated-gsk-moves-to-shutter-sirtris-cambridge-office-integrate-r-d |access-date=August 17, 2017 |archive-date=April 28, 2019 |archive-url=https://web.archive.org/web/20190428120955/https://www.fiercebiotech.com/r-d/updated-gsk-moves-to-shutter-sirtris-cambridge-office-integrate-r-d |url-status=live }}{{Cite web |title=GSK absorbs controversial 'longevity' company: News blog |url=http://blogs.nature.com/news/2013/03/gsk-absorbs-controversial-longevity-company.html |publisher=Nature Blog |access-date=2017-08-17 |archive-date=2013-12-17 |archive-url=https://web.archive.org/web/20131217235120/http://blogs.nature.com/news/2013/03/gsk-absorbs-controversial-longevity-company.html |url-status=live }}.{{Cite news |last=McBride |first=Ryan |date=12 August 2010 |title=Former Sirtris Execs' Nonprofit Starts Selling Resveratrol with Potential Anti-Aging Effects Online |work=Xconomy |url=http://www.xconomy.com/boston/2010/08/12/former-sirtris-execs-nonprofit-starts-selling-resveratrol-with-potential-anti-aging-effects-online/?single_page=true |access-date=17 August 2017 |archive-date=27 March 2019 |archive-url=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 |url-status=live }}{{Cite journal |last1=Kaeberlein |first1=Matt |last2=McDonagh |first2=Thomas |last3=Heltweg |first3=Birgit |last4=Hixon |first4=Jeffrey |last5=Westman |first5=Eric A. |last6=Caldwell |first6=Seth D. |last7=Napper |first7=Andrew |last8=Curtis |first8=Rory |last9=DiStefano |first9=Peter S. |last10=Fields |first10=Stanley |last11=Bedalov |first11=Antonio |last12=Kennedy |first12=Brian K. |date=2005-04-29 |title=Substrate-specific activation of sirtuins by resveratrol |journal=The Journal of Biological Chemistry |volume=280 |issue=17 |pages=17038–17045 |doi=10.1074/jbc.M500655200 |doi-access=free |issn=0021-9258 |pmid=15684413}}

In 2006, Sinclair co-founded of Genocea Biosciences, a company 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;{{Cite news |last=Richtel |first=Matt |date=16 May 2007 |title=Warding Off Diseases, Many Vaccines at a Time |work=The New York Times |url=https://www.nytimes.com/2007/05/16/business/smallbusiness/16genocea.html?mcubz=0 |access-date=26 August 2017 |archive-date=17 August 2017 |archive-url=https://web.archive.org/web/20170817082908/http://www.nytimes.com/2007/05/16/business/smallbusiness/16genocea.html?mcubz=0 |url-status=live }}{{Cite news |last=McBride |first=Ryan |date=May 1, 2008 |title=Polaris' Bitterman is humble about his early VC success |work=Boston Business Journal |url=https://www.bizjournals.com/boston/blog/mass-high-tech/2008/05/polaris-bitterman-is-humble-about-his-early.html |access-date=August 17, 2017 |archive-date=August 17, 2017 |archive-url=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 |url-status=live }} The company delisted from the NASDAQ and closed in 2022 due to lack of funding.{{cite news |last1=Bayer |first1=Max |title=Genocea closes up shop after failing to find a buyer, delists from Nasdaq |url=https://www.fiercebiotech.com/biotech/genocea-closes-shop-after-failing-find-buyer-delists-nasdaq |access-date=9 December 2024 |publisher=Fierce Biotech |date=24 May 2022}}

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.{{Cite web |title=Professor David Sinclair {{!}} School of Medical Sciences |url=https://medicalsciences.med.unsw.edu.au/people/professor-david-sinclair |access-date=2017-11-26 |website=medicalsciences.med.unsw.edu.au |archive-date=2017-12-01 |archive-url=https://web.archive.org/web/20171201035521/https://medicalsciences.med.unsw.edu.au/people/professor-david-sinclair |url-status=live }} In 2008, he also joined the scientific advisory board of Shaklee and helped them devise and introduce a product containing resveratrol called "Vivix". He later disputed the use of his name and words to promote the supplement, and resigned from the board.{{Cite news |last=Goldstein |first=Jacob |date=26 December 2008 |title=Harvard Researcher Tied to Shaklee 'Anti-Aging Tonic' Vivix |work=WSJ |url=https://blogs.wsj.com/health/2008/12/26/harvard-researcher-tied-to-shaklee-anti-aging-tonic-vivix/ |access-date=27 November 2017 |archive-date=1 December 2017 |archive-url=https://web.archive.org/web/20171201041834/https://blogs.wsj.com/health/2008/12/26/harvard-researcher-tied-to-shaklee-anti-aging-tonic-vivix/ |url-status=live }}

In 2011, Sinclair co-founded OvaScience along with Michelle Dipp, Aldrich, Westphal, and Jonathan Tilly. The company was based on scientific work done by Tilly concerning mammalian oogonial stem cells and work on mitochondria by Sinclair.{{Cite web |date=August 29, 2012 |title=OvaScience S-1 |url=https://www.sec.gov/Archives/edgar/data/1544227/000104746912008575/a2210793zs-1.htm |publisher=OvaScience via SEC Edgar |access-date=August 17, 2017 |archive-date=May 14, 2017 |archive-url=https://web.archive.org/web/20170514000041/https://www.sec.gov/Archives/edgar/data/1544227/000104746912008575/a2210793zs-1.htm |url-status=live }}{{Cite news |last=Weintraub |first=Karen |date=December 9, 2016 |title=Can fertility startup OvaScience really help women conceive late in life, as promised? |language=en |work=MIT Technology Review |url=https://www.technologyreview.com/s/603065/rejuvenating-the-chance-of-motherhood/ |access-date=August 17, 2017 |archive-date=February 14, 2017 |archive-url=https://web.archive.org/web/20170214002826/https://www.technologyreview.com/s/603065/rejuvenating-the-chance-of-motherhood/ |url-status=live }} The company merged with Millendo Therapeutics in 2018.{{cite web |title=Once a multibillion dollar company, OvaScience ends a pennystock vehicle for Millendo's reverse merger |url=https://endpts.com/once-a-multibillion-dollar-company-ovascience-ends-a-pennystock-vehicle-for-millendos-reverse-merger/}} In 2011, he also co-founded CohBar along with Nir Barzilai and other colleagues. CohBar aimed to discover and develop novel peptides derived from mitochondria.{{Cite news |last=Grant |first=Bob |date=May 1, 2015 |title=Follow the Funding |work=The Scientist |url=http://www.the-scientist.com/?articles.view/articleNo/42799/title/Follow-the-Funding/ |access-date=January 8, 2022 |archive-date=April 11, 2018 |archive-url=https://web.archive.org/web/20180411122800/https://www.the-scientist.com/?articles.view%2FarticleNo%2F42799%2Ftitle%2FFollow-the-Funding%2F |url-status=live }} CohBar delisted from the NASDAQ upon belief that it was a public shell.{{Cite web |date=2023-11-27 |title=CohBar, Inc.: Notice of Delisting or Failure to Satisfy a Continued Listing Rule or Standard; Transfer of Listing (Form 8-K) |url=https://www.cohbar.com/news-media/press-releases/detail/187/cohbar-inc-notice-of-delisting-or-failure-to-satisfy-a |access-date=2024-05-22 |website=CohBar, Inc. |language=en}}

In 2015, he co-founded Metro Biotech along with Washington University in St. Louis professor Dr. Rajendra Apte. The pharmaceutical company focused on NAD+ precursors such as NMN.{{cite news |last1=Ciardha |first1=Victor |title=A Sneak Peek of Sinclair’s MetroBiotech Lab and New NMN Clinical Trials |url=https://www.nmn.com/news/a-sneak-peek-of-sinclairs-stunning-metrobiotech-lab-and-new-nmn-clincial-trials |access-date=9 December 2024 |publisher=NMN |date=19 June 2024}} He also co-founded Animal Bioscience in 2017 along with his brother Nick. The company focuses on small molecule-based therapy for the pet industry.{{cite news |last1=Kerwin |first1=Nicole |title=Supplement shows potential to reverse aging in dogs |url=https://www.petfoodprocessing.net/articles/17938-supplement-shows-potential-to-reverse-aging-in-dogs |access-date=9 December 2024 |publisher=Pet Food Processing |date=5 March 2024}}

In 2022, 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.{{Cite news | title=In NAC Docket, NAD+ Drug Firm Suggests US FDA Get Serious About Dietary Ingredient Regulations |url=https://hbw.pharmaintelligence.informa.com/RS152012/In-NAC-Docket-NAD-Drug-Firm-Suggests-US-FDA-Get-Serious-About-Dietary-Ingredient-Regulations/ |access-date=2023-01-07 |language=en}} The following year, he co-founded Tally Health, a supplement company with a stated goal to "change the way we age" at the cellular level.{{Cite web |title=Tally Health — Welcome to a New Age. |url=https://tallyhealth.com/ |access-date=2023-03-28 |website=Tally Health |language=en-US}}

In 2024, Sinclair resigned as the President of The Academy for Health and Lifespan Research, an organization made up of a group of scientists that Sinclair had co-founded.{{Cite news |author1=Alex Janin | author2=Dominique Mosbergen | author3=Amy Dockser Marcus |title=Star Scientist's Claim of 'Reverse Aging' Draws Hail of Criticism |url=https://www.wsj.com/health/wellness/david-sinclair-longevity-aging-criticism-645fddc5?mod=hp_lead_pos7 |access-date=2024-04-29 |work=WSJ |language=en-US}} The resignation came after what The Wall Street Journal described as a "cascade" of resignations from outraged members of The Academy after Sinclair and his brother announced that Animal Bioscience had proven that a supplement for dogs with undisclosed ingredients reversed aging. The claim was also met with criticism and skepticism from other longevity researchers.{{Cite web |last=Molteni |first=Megan |date=2024-03-05 |title=Harvard longevity scientist sparks furor with claim about reversing aging in dogs |url=https://www.statnews.com/2024/03/05/david-sinclair-harvard-longevity-scientist-reversing-aging-dogs/ |access-date=2024-03-26 |website=STAT |language=en-US}}

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.{{cite web|url=https://www.technologyreview.com/2022/10/25/1061644/how-to-be-young-again/ |title=How scientists want to make you young again}}

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. 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.

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. This led to publications authored in part by Sinclair in both Nature and Science in 2003. 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.{{Cite news |last=Wallace |first=Benjamin |title=An MIT Scientist Claims That This Pill Is the Fountain of Youth |language=en |work=New York |url=http://nymag.com/scienceofus/2016/08/is-elysium-healths-basis-the-fountain-of-youth.html |access-date=2017-08-17 |archive-date=2017-08-14 |archive-url=https://web.archive.org/web/20170814204010/http://nymag.com/scienceofus/2016/08/is-elysium-healths-basis-the-fountain-of-youth.html |url-status=live }} High-profile papers claiming age reversal of mice have also come under intense scrutiny.{{Cite journal |last1=Gomes |first1=Ana P. |last2=Price |first2=Nathan L. |last3=Ling |first3=Alvin J. Y. |last4=Moslehi |first4=Javid J. |last5=Montgomery |first5=Magdalene K. |last6=Rajman |first6=Luis |last7=White |first7=James P. |last8=Teodoro |first8=João S. |last9=Wrann |first9=Christiane D. |last10=Hubbard |first10=Basil P. |last11=Mercken |first11=Evi M. |date=2013-12-19 |title=PUBPEER Dissection of Anomalies with Figures in Declining NAD(+) induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging |url=https://pubpeer.com/publications/A367937A1FE47F62833BCA961CA087 |journal=PubPeer |language=en |access-date=2020-11-24 |archive-date=2021-03-02 |archive-url=https://web.archive.org/web/20210302140926/https://pubpeer.com/publications/A367937A1FE47F62833BCA961CA087 |url-status=live }} Sinclair's lab has continued to work on resveratrol and analogues of it as part of their research program in anti-aging.

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.{{Cite journal |last1=Lu |first1=Yuancheng |last2=Brommer |first2=Benedikt |last3=Tian |first3=Xiao |last4=Krishnan |first4=Anitha |last5=Meer |first5=Margarita |last6=Wang |first6=Chen |last7=Vera |first7=Daniel L. |last8=Zeng |first8=Qiurui |last9=Yu |first9=Doudou |last10=Bonkowski |first10=Michael S. |last11=Yang |first11=Jae-Hyun |last12=Zhou |first12=Songlin |last13=Hoffmann |first13=Emma M. |last14=Karg |first14=Margarete M. |last15=Schultz |first15=Michael B. |date=2020-12-03 |title=Reprogramming to recover youthful epigenetic information and restore vision |journal=Nature |language=en |volume=588 |issue=7836 |pages=124–129 |doi=10.1038/s41586-020-2975-4 |issn=0028-0836 |pmc=7752134 |pmid=33268865|bibcode=2020Natur.588..124L }} 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.{{Cite web |date=2023-04-23 |title=Life Biosciences Presents Groundbreaking Data at ARVO Demonstrating Restoration of Visual Function in Nonhuman Primates |url=https://finance.yahoo.com/news/life-biosciences-presents-groundbreaking-data-173000353.html |access-date=2024-05-21 |website=Yahoo Finance |language=en-US}}

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.{{Cite journal |last1=Yang |first1=Jae-Hyun |last2=Hayano |first2=Motoshi |last3=Griffin |first3=Patrick T. |last4=Amorim |first4=João A. |last5=Bonkowski |first5=Michael S. |last6=Apostolides |first6=John K. |last7=Salfati |first7=Elias L. |last8=Blanchette |first8=Marco |last9=Munding |first9=Elizabeth M. |last10=Bhakta |first10=Mital |last11=Chew |first11=Yap Ching |last12=Guo |first12=Wei |last13=Yang |first13=Xiaojing |last14=Maybury-Lewis |first14=Sun |last15=Tian |first15=Xiao |date=2023-01-12 |title=Loss of epigenetic information as a cause of mammalian aging |journal=Cell |language=en |volume=186 |issue=2 |pages=305–326.e27 |doi=10.1016/j.cell.2022.12.027 |pmc=10166133 |pmid=36638792}}{{Cite web |title=Scientists Have Reached a Key Milestone in Learning How to Reverse Aging |url=https://www.yahoo.com/lifestyle/scientists-reached-key-milestone-learning-173849420.html |date=2023-01-13 |first=Alice |last=Park |website=www.yahoo.com |language=en-US}} The paper received 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.{{Cite journal |last1=Timmons |first1=James A. |last2=Brenner |first2=Charles |date=2024-02-29 |title=The information theory of aging has not been tested |url=https://linkinghub.elsevier.com/retrieve/pii/S0092867424000503 |journal=Cell |language=en |volume=187 |issue=5 |pages=1101–1102 |doi=10.1016/j.cell.2024.01.013|pmid=38428390 }} Sinclair's claims of reverse aging have received criticism from other scientists.

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.{{Cite journal |last=Finkel |first=Toren |date=2019-09-10 |title=The enlightenment of age |journal=Nature |language=en |volume=573 |issue=7773 |pages=193–194 |doi=10.1038/d41586-019-02667-5 |bibcode=2019Natur.573..193F |doi-access=free}} This was also released as an audiobook on Audible and read by Sinclair.{{Cite book |last=Sinclair |first=David A |url=https://www.audible.com.au/pd/Lifespan-Audiobook/000829237X |title=Lifespan: Why We Age - and Why We Don't Have To |date=10 September 2019 |via=Audible |access-date=22 February 2020 |archive-date=22 February 2020 |archive-url=https://web.archive.org/web/20200222055051/https://www.audible.com.au/pd/Lifespan-Audiobook/000829237X |url-status=live }} 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.{{Cite web |date=2022-05-10 |title=The Anti-Aging Supplements David Sinclair Takes {{!}} Skeptical Review |url=https://novoslabs.com/best-anti-aging-supplements-that-harvard-scientist-david-sinclair-takes/ |access-date=2022-11-16 |website=NOVOS |language=en-US}}

• 2023, [https://www.researchgate.net/profile/Yuancheng-Ryan-Lu/publication/376583494_The_Information_Theory_of_Aging/links/658108cc0bb2c7472bf40381/The-Information-Theory-of-Aging.pdf The Information Theory of Aging], Nature Aging
• 2023, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10373966/ Chemically induced reprogramming to reverse cellular aging], Aging
• 2023, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10166133/ Loss of epigenetic information as a cause of mammalian aging], Cell
• 2021, [https://www.nature.com/articles/s43587-021-00080-0 The economic value of targeting aging], Nature Aging
• 2020, [https://pmc.ncbi.nlm.nih.gov/articles/PMC7752134/ 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

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Category:Australian biologists

Category:Australian geneticists

Category:Australian expatriates in the United States

Category:Australian people of Hungarian descent

Category:Living people

Category:Life extensionists

Category:Longevity researchers

Category:Biogerontologists

Category:Harvard Medical School faculty

Category:1969 births

Category:University of New South Wales alumni