David Sinclair
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David Andrew Sinclair is an Australian teacher of genetics at Harvard University who specializes in the study of anti-aging. After meeting researcher Leonard Guarente, Sinclair worked with him as a post-doctoral student and began to study the genetic and non-genetic reasons for aging. After years of research, Sinclair founded Sirtris Pharmaceuticals in 2004 to research the re-activation of molecules that supposedly prevent aging, known as sirtuins.
The research he did suggested that the compound resveratrol would help reverse aging and was found primarily in red wine. In studies he had done, he was able to extend the life of small animals, though later studies on humans did not yield a medical product. In the last decade, Sinclair has founded or been a part of several startups focused on different aspects of anti-aging, from replicating the effects of cardiovascular exercise, or the effects of a healthy diet, as well as attempting to disrupt the aging process itself. He has become a well known expert in the field, often being interviewed, and noted for his research.
Contents
Biography
Early life and education
Sinclair grew up in Saint Ives Australia, and since the age of four, has been “obsessed” with “the gravity of life”. Interested in science from an early age, he experimented with making bombs from chlorine or gunpowder. Later he attended the University of New South Wales, and studied gene regulation in yeast.
While attending college, he attended a lecture by a visiting researcher named Leonard Guarente, whose area of focus was in molecular biology at the Massachusetts Institute of Technology. Sinclair ended up joining Guarente’s lab as a post doctoral student in 1995. After four years, Sinclair was offered a position with Elixir Pharmaceuticals which his colleague and mentor Guarente had cofounded.
Business career
Sirtris Pharmaceuticals
In 2004, Sinclair convinced philanthropist Paul Glenn to donate five million dollars to start an institute to study aging at Harvard, which Sinclair became director of. That same year, Sinclair cofounded a biotechnology company called Sirtris Pharmaceuticals with the assistance of Kevin Bitterman, a researcher at Harvard Medical School who had studied under Sinclair. In May 2007, Sirtris completed its initial public offering and raised 62 million dollars.
Sinclair’s company became one of the biggest in anti-aging research largely due to their work on a compound called resveratrol and their attempt at an anti-aging product called SRT501. This compound contained molecules that the lab claimed would be able to activate sirtuins which would reverse the aging process. Animal testing had shown their was potential for the formula to treat diabetes and neurological disorders, and human trials were planned to see if it affected Melas disease, which caused accelerated again as well as brain and muscle deterioration.
Sirtris Pharmaceuticals was sold in 2008 for 720 million to GlaxoSmithKline, of which Sinclair received eight million. A drug using resveratrol and other compounds were tested by Sirtris in clinical trials over several years, but a drug that would help with diabetes or other diseases was not identified. GlaxoSmithKline ended research into resveratrol in 2010 because of its low efficacy and side effects. Sirtris’s existence as an independent unit ended in 2013 when it was absorbed into GlaxoSmithKline.
Philanthropy
During the COVID-19 pandemic, David Sinclair donated Polymerase Chain Reaction (PRC) kits to coronavirus testing facilities.
Other endeavors
During his time before and after his involvement with Sirtris Pharmaceuticals, Sinclair was regularly involved with other scientific startups and research groups. In 2008, he was invited to join the scientific advisory board of Shaklee, a supplement company selling a product called “Vivix”, a grape-flavored anti-aging supplement. In the early 2010’s, Sinclair’s existing Harvard anti-aging lab came into money trouble due to budget cuts and smaller grants from the National Institutes of Health, having to cut the amount of researchers from eighteen to four or five in order to keep from shutting down. In 2015, Sinclair was funded by the United States Department of Defense to research survival and recovery of soldiers on the battlefield, and in 2018 he started “Arc Bio”, a tech startup with researchers from Harvard University and Stanford University, to develop a disease database to help stop outbreaks and reduce laboratory testing time. Also in 2018, he worked with “Rejuvenate Bio”, a startup working to extend the life of, and cure diseases found in, dogs. Sinclair is also an investor in a company called “InsideTracker”, which attempts to measure peoples lifespans.
Research
One of the main focus’s of Sinclair’s research has been his work on a compound called resveratrol, with which he was able to extend the life of mice by twenty-four percent, and fifty-nine percent in flies and worms. The mice used in this study were overweight, yet their longevity was as long as the mice of normal weight, most likely due to increased insulin sensitivity. Mice, along with other animals with shorter lifespans such as worms and fruit flies are often used in Sinclair’s research as human trails of medicines can take decades for results. Early in his research, Sinclair screened many food products to see which held the highest amounts of resveratrol, finally settling on red wine. That the chemical is found in red wine was at least initially thought to help explain the “French Paradox”, which is shorthand for the observation that French life expectancies are not lower than normal despite a generally heavy diet of fatty foods.
Sinclair’s work has also focused upon calorie restriction, and during his research, he identified genes that made yeast consume fewer calories, yet live 30% longer. Sinclair has stated his belief that calorie restrictive diets cause the body to focus on self repair, and that a compound found in cells called Nicotinamide adenine dinucleotide (NAD+) could be used to induce this repair state in the body even without calorie restriction. In 2013, Sinclair published a study claiming that a family of proteins called sirtuins, which help regulate other cells, became overwhelmed with DNA repair work over time, and were then unable to read genetic information due to a lack of NAD, leading to aging. To test this theory, one experiment involved “breaking” mouse DNA to see if it accelerated aging. As humans age, they produce less and less NAD, and Sinclair believes that NAD supplementation could reverse aging caused by this process. A 2017 study conducted on mice being given “NAD+” in their water resulted in the mice acting and looking younger. Sinclair has tried to commercialize molecules known as “NAD boosters” which he claims help with life span extension.
Sinclair has also used a compound called Nicotinamide mononucleotide (NMN) to help promote the creation of blood vessels near muscles and organs, causing a sixty percent increase in the treadmill running ability of the test mice. As resveratrol attempted to replicate a healthy diet, NMN is seemingly attempting to chemically replicate the effects of increased cardiovascular health.
Sinclair believes that aging should be labeled a “disease”, not only in order to free up funding in the medical community that reserves most research for the study of disease, but to treat the many disorders and diseases that are occurring due to what Sinclair views is their root cause; aging. In this way, instead of treating many diseases in a “whack a mole” fashion, Sinclair believes that scientists can go right to the source and make it possible for humans to live to 150 years old. In the meantime however, Sinclair’s focus is to deal with illnesses such as heart disease, cancer, diabetes, and dementia through his NAD treatment.
Personal life and diet
Sinclair is regarded by some of his colleagues as very persuasive, but sometimes lacking the patience and having too much passion for a scientist. His mentor Leonard Guarente has called him a “bold scientist”, who is willing to take chances and try risky experiments”.
Sinclair’s diet has changed because of his research; he eats more vegetables than meat, and takes supplements including resveratrol and an NAD compound. He believes in a practice called “hormesis”, which involves introducing metabolic stress by intermittent fasting and metabolic stress. He has summed up this approach as “Every day, try to be hungry and out of breath”.
With his own medical products, Sinclair believes he has extended his biological clock by two decades. He also estimates that at least a third of his colleagues are taking experimental anti-aging molecules.
Publications, media, and awards
In 2019, Sinclair and journalist Matthew LaPlante released a book entitled Lifespan: Why We Age - and Why We Don’t Have To, which discussed not just the medical ways human lifespans could be extended, but the societal and ethical implications of such an occurrence. Sinclair is noted in the book as calling aging a “disease”, a concept not widely agreed with in the medical community, but one which Sinclair claims has restricted funding for anti-aging research. On October 6, 2019, Lifespan was number twelve on the New York Times Best Seller List under “Hardcover Nonfiction” books. Sinclair has received honors for his research, such as his inclusion as one of Time Magazines 100 Most Influential People of 2014, and as part of their “Healthcare 50” in 2018.
