Living longer usually means a longer dotage, but wouldn’t it be enticing to extend young adulthood instead?
It’s such an appealing prospect that scientists who are announcing success with roundworms are keen to be clear they are a long way from achieving it in humans.
“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 Michael Petrascheck of the Scripps Research Institute in California, lead author of a report on the findings.
“There are millions of years of evolution between worms and humans,” he added. But “we think it is exciting to see that extending lifespan by extending young adulthood can be done at all.”
In the study to be published in the journal eLife, the researchers administered an antidepressant called mianserin to Caenorhabditis elegans, a type of roundworm used often in research. In 2007, they discovered that the drug increases the lifespan of roundworms by 30-40 per cent. Their new goal was to investigate how.
The team treated thousands of worms with either water or mianserin and looked at the activity of genes as the worms aged. First, they measured the activity of genes in young adults as a reference point against which to monitor the aging process. Reproductive maturity begins in day-old roundworms and they live for 2-3 weeks on average.
As the worms aged, the team measured dramatic changes in gene expression, or the activation pattern of various genes. But the changes occurred in a totally surprising way, the investigators said. Groups of genes that together play a role in the same function were found to change expression in opposing directions.
“Genes related to the same function were going up and down at the same time,” Petrascheck explained. The team has called the newfound phenomenon “transcriptional drift” and said they confirmed that it also occurs in mammals.
“Transcriptional drift can be used as a new metric for measuring age-associated changes that start in young adulthood,” said Sunitha Rangaraju, one of the authors of the study.
The study found that mianserin can suppress transcriptional drift, but only when administered at the right time of life. By 10 days old, treated worms still had the gene expression characteristics of a three-day-old—physiologically they were seven days younger, the researchers explained. But by 12 days, the physiological changes required to extend lifespan were complete and lifelong exposure to the drug had no additional effect. Mortality rates were shifted parallel by 7-8 days across the treated worms’ lifespan, confirming the finding.
Only the young adulthood period was extended, the researchers said.
“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,” said Petrascheck. But “we are already excited about the fact that we observed the phenomenon of transcriptional drift in species ranging from worms, mice to humans.”
The investigators plan to test the effect in mice next.