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December 02, 2015

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Scientists accidentally extend young adulthood in worms using drug

Dec. 2, 2015
Courtesy of ELife
and World Science staff

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.


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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 frequently 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 way that came as a complete surprise, he 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,” said Petrascheck The team has called this 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. Mianserin blocked signals related to the regulation of serotonin and this delayed physiological changes associated with age, including the newly identified transcriptional drift and degenerative processes that lead to death. The effect only occurred during young adulthood and the duration of this period of life was significantly extended. “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. “However, we are already excited about the fact that we observed the phenomenon of transcriptional drift in species ranging from worms, mice to humans.” The findings have opened up many new avenues of research for the team and are likely to spawn a wealth of research by others, the group added. They plan to test the effect in mice, for example. drug