Turning Off "Aging Genes"
Some of the genes that the MTA identified were already known to extend the lifespan of yeast when turned off. Of the other genes she found, Yizhak sent seven to be tested at a Bar-Ilan University laboratory. Researchers there found that turning off two of the genes, GRE3 and ADH2, in actual, non-digital yeast significantly extends the yeast's lifespan. "You would expect about three percent of yeast's genes to be lifespan-extending," said Yizhak. "So achieving a 10-fold increase over this expected frequency, as we did, is very encouraging."
Hope for humans
Since MTA provides a systemic view of cell metabolism, it can also shed light on how the genes it identifies contribute to changes in genetic expression. In the case of GRE3 and ADH2, MTA showed that turning off the genes increased oxidative stress levels in yeast, thus possibly inducing a mild stress similar to that produced by calorie restriction.
As a final test, Yizhak applied MTA to human metabolic information. MTA was able to identify a set of genes that can transform 40-to-70 percent of the differences between the old and young information from four different studies. While currently there is no way to verify the results in humans, many of these genes are known to extend lifespan in yeast, worms, and mice.
Next, Yizhak will study whether turning off the genes predicted by MTA prolongs the lifespan of genetically engineered mice. One day, drugs could be developed to target genes in humans, potentially allowing us to live longer. MTA could also be applied to finding drug targets for disorders where metabolism plays a role, including obesity, diabetes, neurodegenerative disorders, and cancer.