Plenty of people wish to live longer than the scant time we’re allotted, but currently, longer life mostly means an extended period of seniority. An extended youth, therefore, is extremely appealing—and scientists have taken a fascinating step in this direction by granting roundworms 30-40% more time as “youths”.
The study, which has been published in the journal eLife, follows in the footsteps of a major discovery made in 2007: Mainly, that the antidepressant mianserin extended the lives of Caenorhabditis elegans, a commonly-studied roundworm otherwise known as a nematode.
What’s going on with these worms?
But it wasn’t exactly clear how these drugs affected the worms. How did it change genes? And what part of life did it extend?
And so, a team from The Scripps Research Institute in California administered either water or mianserin to thousands of the roundworms, while examining the activity of their genes. Naturally, as the untreated worms aged, their gene expression changed—but one of the biggest surprises found was how this changed.
In some groups of genes that work together to perform a function, the expression levels of the various genes were found to shift in the opposite directions with age: Some were expressed more, and some were expressed less. This new phenomena has been termed “transcriptional drift,” and was confirmed by the team to happen in mice, humans, and other mammals.
“The orchestration of gene expression no longer seemed coordinated as the organism aged and the results were confusing because genes related to the same function were going up and down at the same time,” lead author Michael Petrascheck said in a statement.
This lack of coordination might prove to be a very useful discovery.
“Transcriptional drift can be used as a new metric for measuring age-associated changes that start in young adulthood,” said first author Sunitha Rangaraju. “Until now we have been dependent on measuring death rates, which are too low in young adults to provide much data. Having a new tool to study aging could help us make new discoveries, for example to treat genetic predispositions where aging starts earlier, such as Hutchinson-Gilford progeria syndrome.”
Knowing this new metric, the researchers discovered that mianserin suppressed transcriptional drift in the nematodes—but only if given at the right time. C. elegans usually lives for two to three weeks, but after 12 days of age, the antidepressant no longer had additional effects.
However, if given at the age of three days, the worms were found to have the same gene expression characteristics at 10 days—meaning transcriptional drift had more or less frozen for seven days. Physiologically, the 10-day-old worms were three days old—and they died a parallel seven to eight days later than nematodes treated with water alone.
In other words, the worms lived as youths for a longer period of time, but aged the normally after the blush of youth faded, granting them an overall longer life.
Don’t try this at home
Of course, this doesn’t mean young human adults should be dosing themselves with mianserin.
“We don’t want people to get the impression they can take the drug we used in our study to extend their own teens or early twenties,” said Petrascheck. “We may have done this in worms, but there are millions of years of evolution between worms and humans.”
The next step for the team is to investigate the effect of the antidepressant on mice, where they will keep a sharp eye out for side effects. They also aim to explore how it would affect different organs in the body.
“How much of our findings with regards to lifespan extension will spill over to mammals is anyone’s guess, for example the extension of lifespan might not be as dramatic,” added Petrascheck. “However, we are already excited about the fact that we observed the phenomenon of transcriptional drift in species ranging from worms, mice to humans.”
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Feature Image: Thinkstock
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