The idea of living way beyond our expected years is tantalizing to many, but is it really desirable to be elderly for even longer? In an ideal world, we could draw out our younger, prime years and then age healthily, and while we’re no way near achieving this with humans, some intriguing work on animals is telling us never say never.
Described in the open-access journal eLife, scientists from The Scripps Research Institute (TSRI) found that an approved antidepressant drug changed the way genes were expressed in roundworms as they aged, maintaining patterns that the animal displayed during young adulthood.
“People have often observed that animals look younger when their life is experimentally extended, but so far it’s not been possible to figure out whether this is a proportional life extension, or if just one period is stretched out,” lead author Michael Petrascheck told IFLScience. “What we think is most interesting, most different, is that this drug specifically extends the duration of young adulthood. It doesn’t do anything to an animal that’s already aged.”
This research follows on from a previously published paper in which the team decided to screen 88,000 different compounds to identify any with potential life-extending properties. More specifically, they wanted to find those that appeared to be able to disrupt so-called “serotonergic” signaling of the nervous system, or messages sent between cells in the form of the “happy hormone” serotonin.
This led them to the antidepressant drug mianserin, which was found to extend the lifespan of the model animal Caenorhabditis elegans, or the roundworm, by about 30 to 40 percent. For the present investigation, the team wanted to find out how precisely the drug achieves this, so they began by first monitoring how gene expression patterns change as the worm ages. When a gene gets expressed, the stretch of DNA gets turned into an RNA “transcript” that serves as a template for the generation of a particular protein.
What they found was that groups of genes that together perform a particular function, orchestrated in their expression, began to drift apart as the animal aged. Some genes went up in expression, others went down. This lack of coordination was found to be detrimental to the gene pathway affected by this phenomenon, which they coined “transcriptional drift.” After plowing through data on mice and humans, they found that mammals also undergo this same process.
What was surprising, though, is that mianserin seemed to be preventing these age-associated changes in gene expression, maintaining youthful patterns for much longer than you’d see in a normal animal. This only occurred, though, if the drug was administered to young worms; it couldn’t reverse the aging process in elderly animals.
“It’s like an orchestra where people start to progressively play to a different beat,” said Petrascheck. “The drug is the conductor that keeps them all together.”
The researchers think this has to do with the ability of the drug to block serotonergic signaling. Serotonin is a food signal in these worms, Petrascheck explained, and dietary restriction has been found to extend life. So maybe the drug is preventing the worm’s nervous system from realizing it has eaten, and that’s enough to extend its life.
More work is to be done, and the obvious question is whether similar effects would occur in humans, but for now it’s impossible to say. An interesting way to take this study forward, though, would be to see if it could possibly reduce or delay the onset of age-related diseases.
Image in text: C. elegans worms at young adulthood, imaged by Sunitha Rangaraju. eLife 2015.