Antidepressants Extend The Lives Of Roundworms By Flipping Genetic Switches

Though many entrepreneurs and innovators are working to extend the human lifespan, there’s a good chance that much of that borrowed time might be spent in poor health. Now researchers might have found a way to extend adolescence and young adulthood because of some quirky changes in gene expression brought on by an antidepressant, at least in roundworms. The researchers published their findings yesterday in the journal eLife.

During a different study in 2007, the researchers discovered that treating the roundworm Caenorhabditis elegans with a common antidepressant compound called mianserin helped the worms live 30 to 40 percent longer. This time, the researchers wanted to figure out why that happened. They were paying special attention to gene expression—whether or not genetic blueprints are used and can change throughout an organism’s life—of a particular set of genes that, if turned on, were known to cause many of the effects of aging.

The researchers divided thousands of roundworms into three groups and gave each a dose of mianserin at a different time in their development into adulthood. After a few days, the researchers looked at how the gene expression changed for each group, using an analytical method called the gene-set enrichment analysis.

On all the worms, mianserin had some surprising effects on the worms’ gene expression. Think of genes as a long line of light switches that can be turned off or on. Typically, throughout an organism’s life, one or two genes might get switched on or off at a time. When the roundworms were treated with mianserin, the drug affected a group of switches that affect all the lights in one room (or function of the body), but instead of flipping them all off, or freezing them in place, the drug caused each one to switch position. The expression of the “off” genes in that group was turned on, and the “on” genes were turned off. The most profound effects on the worms’ genetic expression were in those treated with mianserin earliest.

The researchers called this switch-flipping phenomenon “transcriptional drift,” and the shift of expression disrupted the typical, coordinated process of aging. They suggest that measuring transcriptional drift might be a way to quantitatively measure age-related changes that start in early adulthood.

This isn’t the first study to show that changes in gene expression can lengthen a roundworm’s lifespan. And though this may make us hopeful for immortality, the researchers remind us that though roundworms make a great model organism, but there are “millions of years of evolution” between roundworms and humans, they say in a press release. In future studies, the researchers plan to look at transcriptional drift in mice and human brains, which may bring the prospect of extended youth a bit closer to home.