David A. Sinclair
Geneticist of aging at Harvard Medical School, known for work on sirtuins, NAD+ and the idea that aging stems from a loss of epigenetic information, who appears in this Atlas as a co-author on two mouse lifespan studies
Professor of Genetics, Harvard Medical School, and founding director, Paul F. Glenn Laboratories for the Biological Mechanisms of Aging · conjoint professor, School of Medical Sciences, University of New South Wales · faculty, Harvard Medical School (since 1999) · postdoc, Leonard Guarente lab, MIT · PhD in molecular genetics, University of New South Wales (1995)
Portrait: Sinclair Lab, Harvard Medical School
David Sinclair is a middle author on two Atlas studies about diet, drugs and lifespan in mice. SOL2014, led by Samantha Solon-Biet and Stephen Simpson in Sydney, fed mice diets that differed in their mix of protein, carbohydrate and fat and let them eat freely. Lifespan and heart and metabolic health depended on the ratio of protein to carbohydrate, not on the total calories eaten, and mice on low-protein, high-carbohydrate diets had lower mTOR activation in the liver. STR2012, from the NIA Interventions Testing Program, tested five popular candidates, including resveratrol, green tea extract and curcumin, in genetically mixed mice. None changed lifespan significantly. The paper is a clear example of publishing negative results, which helps others avoid chasing compounds that do not work.
Sinclair earned his PhD in molecular genetics at the University of New South Wales in 1995, studying gene regulation in yeast. He then spent about four years in Leonard Guarente's lab at MIT, where yeast was used as a model of aging, and joined Harvard Medical School in 1999. His lab has worked on sirtuins, a family of enzymes that need the molecule NAD+, on mitochondria, and on partial reprogramming with Yamanaka factors to restore youthful gene activity in mouse tissues. He proposes an 'information theory of aging', in which aging comes from a gradual loss of epigenetic information, the chemical marks that tell each cell which genes to use.
He is Professor of Genetics at Harvard Medical School, founding director of the Paul F. Glenn Laboratories for the Biological Mechanisms of Aging, and a conjoint professor at the University of New South Wales. Some of his claims, including early work on resveratrol as a sirtuin activator and public statements about reversing aging, have been disputed by other researchers.
Milestones in the Atlas
A selection, not a full bibliography: only papers that meet the Atlas inclusion criteria.
| Year | Evidence | Study |
|---|---|---|
| 2012 | A | Evaluation of resveratrol, green tea extract, curcumin, oxaloacetic acid, and medium-chain triglyceride oil on life span of genetically heterogeneous mice STR2012 Co-author on the Interventions Testing Program report in which none of five popular compounds, including resveratrol, extended mouse lifespan significantly. |
| 2014 | A | The ratio of macronutrients, not caloric intake, dictates cardiometabolic health, aging, and longevity in ad libitum-fed mice SOL2014 Co-author on the mouse study showing that the protein-to-carbohydrate ratio, not calorie intake, shaped lifespan and metabolic health, with lower liver mTOR activation on low-protein diets. |
Co-authors in the Atlas 8
People with a profile here who share at least one study with David A. Sinclair.
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- Clinton Astle Long-time research associate of David Harrison at The Jackson Laboratory, with work on mouse blood stem cells and aging since the 1970s, and a co-author of the Interventions Testing Program papers that showed rapamycin extends mouse lifespan
- David E. Harrison Led the Jackson Laboratory site of the NIA Interventions Testing Program. His 2009 Nature paper showed that rapamycin extends the lifespan of genetically diverse mice even when feeding starts at 20 months of age, which the authors described as the first pharmacological extension of lifespan in both sexes of a mammal
- James L. Kirkland Founder of the field of senolytics, drugs that clear senescent cells, and a leader of clinical trials of ageing-targeted therapies
- Nancy L. Nadon Scientist and programme official at the US National Institute on Aging who oversaw research resources for aging biology and helped run the Interventions Testing Program that found rapamycin extends mouse lifespan
- Randy Strong Leads the San Antonio site of the NIA Interventions Testing Program, which tests each compound in parallel at three sites under one shared protocol. He first-authored the program's reports on resveratrol and other supplements (2012) and on rapamycin combined with acarbose (2022)
- Richard A. Miller Leads the University of Michigan site of the NIA Interventions Testing Program. His papers showed that rapamycin extends mouse lifespan when started in middle age, and that the size of the benefit depends on dose and differs between males and females
- Samantha M. Solon-Biet Nutrition and ageing researcher at the Charles Perkins Centre who uses the Geometric Framework to study how protein, carbohydrate and fat intake affect lifespan, metabolism and reproduction in mice
- Stephen J. Simpson Biologist who began with how locusts choose their food and is known for the Geometric Framework for nutrition, which shows that the balance of protein, carbohydrate and fat shapes health and lifespan; inaugural academic director of the Charles Perkins Centre
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