Fifteen years ago David Sinclair moved half way around the world to pursue his interest in longevity. David didn't want to take the usual route, looking for the genes that ended life, he wanted to figure out how to extend it.
Today he strives to devise ways to prevent and treat major diseases by manipulating genes that control how fast we age. David has been a frontrunner in the dramatic shift in research related to the aging process. Ignoring the conventional wisdom that the aging process was too complex to find drugs that could slow it, he works to uncover single genes that could dramatically extend the lifespan of laboratory organisms such as yeast, worms, flies and mice.
This transformation has left us with the fact that the rate of aging is not predetermined - it is naturally regulated by a few critical genes. These genes underlie the remarkable effects of the diet known as calorie restriction (CR), which delays aging in nearly every species tested, from yeast to primates. According to Dr. Sinclair, CR is currently the only treatment that is proven to prevent all diseases of aging including cancer, heart disease, osteoporosis, diabetes and neurodegeneration.
In his own words: "Recent studies in our lab and others demonstrate that the ability of CR to extend lifespan in model organisms is governed by the Sirtuins.* Animals lacking Sirtuin genes do not respond to CR while additional gene copies extend lifespan. Based on these findings, we have engineered small molecules that can activate mammalian Sirtuins in vivo, with a view to developing drugs that can:
1. Treat the diseases of aging and
2. Promote cell survival and recovery following an injury.
We utilize any approach we need to answer a specific question including chemistry, biochemistry, genetics and cell biology. Models systems include yeast, C. elegans, mammalian cell culture and rodents."
Current Work with Resveratol and other SIRT1 Activating Compounds (STACs)
David has been working with Rafael deCabo, National Institute on Aging of the National Institutes on Health, using CR, resveratrol, and molecules 1000 times more potent than resveratrol to delay diseases of aging and extend the healthspan of mice. Resveratol is found in the skin of red grapes. News about the health benefits of red wine, and resveratol, have made headlines in recent years, often related to the work of David's lab. Currently David and Rafa are testing the hypothesis that they will "see significant lifespan extension in mice started on the molecules at a younger age, and using the more potent SIRT1** activators that Sirtris has developed." Sirtris is the company David Sinclair co-founded to explore sirtuin research, it is now owned by GlaxoSmithKline. Sirtris is in clinical trials in 2009 and 2010 to test their potent SIRT1 activators in a variety of diseases of aging including type II diabetes.
A recent article in Cell, co-authored by David Sinclair, postulates that changes in gene expression and chromatin structure might underlie aging. Read it here.
* Sirtuins are a recently discovered family of seven enzymes associated with the aging process.
**SIRT1 is a sirtuin