The findings in the new study, which is published in the November issue of the journal Cell Metabolism, also answer a big scientific question: whether scientists searching for ways to combat aging have been targeting the right gene.
SRT1720, like resveratrol, works by targeting a gene known as sirtuin 1, or SIRT1, which many scientists believe plays a fundamental role in regulating life span. SIRT1 encodes for a class of proteins known as sirtuins, and it is a central controller of mitochondrial activity (mitochondria are the powerhouse energy providers to the cells). “Firing up mitochondria is one of the best treatments against diabetes and obesity because you burn off extra energy instead of storing it,” notes Auwerx.
However, unlike the new compound, resveratrol is not specific to SIRT1, and thus many experts have questioned whether the effects of resveratrol in mice were mediated by SIRT1 activation or by some other pathway.
The fact that another chemical activates the same gene and produces similar effects strongly suggests that the metabolic benefits can be attributed to SIRT1, says Leonard Guarente, an MIT biologist whose lab first discovered the sirtuin 1 gene. He is on Sirtris’s advisory board but wasn’t involved in the study. “This is a very important finding, and [it] means that [SIRT1 activators] are good candidates for lead compounds [in] antidiabetic drugs in humans,” Guarente says. SIRT1 could also be a target for other diseases related to aging, he adds, “which would be a silver bullet.”
“The scientific community is focusing on mitochondria as the most important organelle in muscle that affects the risk of diabetes, hypertension, and the loss of physical function in elderly people,” says Evans. “The compound may be one additional help or aid that we could use to treat these conditions. It is an exciting, new development.”
Sinclair says that a cousin molecule of SRT1720, which is even more potent, is currently in human trials and will enter clinical studies for the treatment of diseases like type 2 diabetes in 2009. “We could know as early as next year if the same types of benefits we see in mice, we see in humans,” he says.