David Sinclair

David Sinclair, PhD

Personal information Born June 26, 1969 (age 50) Sydney, Australia Nationality Australian Education University of New South Wales (BS, PhD) Field of study Molecular genetics Occupation Professor, author, entrepreneur Position co-Director of the Paul F. Glenn Center for the Biology of Aging at Harvard Medical School

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. These startups range 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.

Biography

Early Life and Education

Sinclair grew up in Saint Ives, Australia. From a young age, he actively explored his vast backyard and studied birds, plants, and reptiles, and was fascinated with how things work. Sinclair stated that since the age of four, he has been "obsessed" with "the gravity of life." Interested in science from an early age, he experimented with making bombs from chlorine or gunpowder.

Sinclair's grandmother, his greatest inspiration, was a bohemian, who ran a hotel in Hungary until the Nazis converted it into a headquarters for the SS. Sinclair's great grandmother tried to cross the Soviet borders of Hungary in the mid-1950s, and was sentenced to two years in prison, and died shortly after release. His grandmother was an anti-Soviet activist, but after the failed uprising in 1956, she fled to Australia. She impressed upon Sinclair and his sibling that six was the best age to be and to keep the feeling of youth as long as he lived.

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 co-founded.

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 was a thousand times as potent as resveratrol, and 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 had to deal with lower federal funding in the late two-thousands, with Sinclair’s lab being reduced from eighteen personnel to four. The company 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.

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 2015, Sinclair was funded by the United States Department of Defense to research survival and recovery of soldiers on the battlefield and three years later 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. Sinclair co-founded a company called Life Biosciences in 2017 and raised over seventy-five million dollars in its first two years. 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. In 2018, NASA granted Sinclair and a colleague a Post-Doctoral Award for his proposal to study the boosting of NAD to protect against the loss of musculature around the bones while in space.

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

Some of his colleagues regard Sinclair 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 mother fell ill, having already lost her joy of life, and experienced suffering before dying. Sinclair became more determined than ever to extend not only the length of life but the youthful portion of life.

Sinclair's diet has changed because of his research; he eats more vegetables than meat, and takes supplements, including resveratrol and a 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 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

• 148 Publications produced by The Sinclair Lab

In 2018, Sinclair became an officer of the Order of Australia. In 2019, Sinclair and journalist Matthew LaPlante released a book entitled Lifespan: Why We Age - and Why We Don't Have To. This book discusses not just the ways medicine could extend human lifespans, but the societal and ethical implications of such an occurrence. Sinclair calls aging a "disease" in the book, a concept not widely agreed with among the medical community. This designation has restricted funding for anti-aging research, according to Sinclair. On October 6, 2019, Lifespan was number twelve on the New York Times Best Seller List under "Hardcover Nonfiction" books.

Media

Sinclair has appeared on many television and radio shows, as well as podcasts such as "The Joe Rogan Experience."

Awards

Sinclair has received honors for his research, such as inclusion as one of Time Magazines 100 Most Influential People of 2014, and as part of their "Healthcare 50" in 2018.

External links

• Twitter
• Facebook
• Instagram
• LinkedIn
• ORCHID
• Harvard Catalyst
• The Sinclair Lab
• Life Span (Book)
• Sinclair Lab Publications
• Harvard Medical Biography
• Scholarly Publications