Last December, we brought you the news of a study led by David Sinclair that was published in Cell. The study claimed to not only slow down the aging process in mice, but actually reverse it by administering NAD+, which Sinclair claimed affected how the mitochondrial DNA regulated aging. If the same results were achieved in humans, it would have been like a 60-year-old regaining the body of a 20-year-old. Human trials were expected to begin this year, but the road to drug development is not always smooth, and some significant bumps derailed progress.
Though GlaxoSmithKline acquired the biotech firm Sirtris in 2008, which was co-founded by Sinclair, there wasn’t a lot of support to fund human clinical trials of the anti-aging drug. From the first stage of bringing a new drug to human trial all the way to getting it approved, the total bill can run hundreds of millions of dollars. GSK had some reservations about moving forward with the research for several reasons. The target itself was extremely sensitive and they didn’t want to rush human trials, there was a fair amount of criticism of Sinclair’s earlier work in terms of reproducibility, and claims that the work was inherently flawed because the molecular mechanisms were misrepresented.
The controversy surrounding Sinclair’s studies are partially based on whether or not the NAD-dependent gene Sirtuin-1 (SIRT1) is activated by a small family of sirtuins developed by Sirtris. These drugs include SRT1460, SRT1720, SRT2183, and resveratrol, and are reported to regulate transcription of the genes involved with aging, apoptosis, and metabolism. Studies from Sinclair have shown that these drugs have considerable positive effects not only with aging, but also with type 2 diabetes. However, a study published in the Journal of Biological Chemistry concluded that these drugs are not direct activators of SIRT1, which would render Sinclair’s work fundamentally inaccurate.
Last March, it was announced that GSK would be shutting down Sirtris after a five year run. Though some of the scientists and drugs were retained and transferred to other GSK facilities, much of their focus in the anti-aging, anti-inflammatory arena will focus on SRT2104.
Through all of this, Sinclair never lost faith in the integrity of his work and kept working, even after his funding had been pulled. Earlier this month, he was a co-author of a paper that was published in the journal Cell Reports. The results of this study reaffirm that SRT1720 does activate SIRT1 directly, with some impressive metabolic claims. Even when fed a traditional Western diet, mice were shown to have a decrease in fat mass, cataracts, and inflammation, while showing an increase in cardiac function, muscle function, an an 8.8% increase in lifespan (in humans, this would be like getting 7 extra good years of life).
Sinclair is still working toward getting his drugs into human trials, though the future is fairly uncertain at this point.
