RNA pathway plays key role in health,lifespan, fly study shows21 December 2016

Green fluorescence shows where transposable elementsare moving about in this fly's fat body cells in theabsence of a fully in tact piRNA pathway. Credit: BrianJones/Brown University

Humans and other animals carry rogue sequencesof DNA in their genomes called transposableelements (TEs). To prevent passing TEs to theiroffspring, they employ the piRNA pathway in theirreproductive organs to block the elements frombeing active in their sperm and eggs. With a newstudy in flies, Brown University biologists are thefirst to show that the anti-TE activity of the piRNApathway also operates in a normal non-reproductive body tissue, the fly fat body, and thatit helps to sustain the life of the animal.

"It's required for normal health and longevity," saidDr. Stephen Helfand, senior author of the study in Nature Communications and a professor of biologyat Brown University.

Most previous reports of piRNA at work outside of reproductive organs were in cancer or stem cells,with one study suggesting it may also be present ina subset of adult fly neurons, but no one had evermeasured its consequences in normal health andaging.

In experiments led by Brown graduate student BrianJones, the research team tracked severalcomponents of the pathway, such as the presenceof piRNAs and the expression of associated "piwi"and "flamenco" genes, in the fat body tissue of flies.The fat body is akin to adipose and liver tissues inmammals and also contributes to flies' immunesystems.

Significant health effects

Once the researchers confirmed that the piRNApathway was active in a normal, mature bodytissue, they conducted several experiments to seewhat happened in the flies when they knockedcomponents of the pathway out. For example, withthe piwi gene gone, flies had significantly fewerpiRNAs than flies who had a copy.

To see if a compromised pathway led to uncheckedtranscription of TEs, the researchers used amethod that makes cells glow green whenparticular TEs move around within the genome.Flies without piwi lit up brightly.

By other measures, the researchers found that piwi-lacking flies experienced increased DNA damagecompared to flies with a working piwi gene, andflies lacking in either piwi or flamenco had less fatthan controls. Flies without piwi succumbed tostarvation more quickly, and flies with either of thegenes knocked out lived considerably shorter livesthan flies with a working copy of both genes.

Specifically, about four in five flies with a workingpiwi gene were still alive at 60 days of age, butvirtually all of the piwi-lacking flies were dead longbefore then. Among flies with a flamenco geneintact, about half were still alive at 60 days, whilethose lacking any flamenco had died off.

In one more experiment, the team tested whether ahuman HIV drug called 3TC or lamivudine, whichblocks the step needed to make more transposable

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element DNA, could rescue flies without flamenco. Itdid to a significant extent, allowing many flieslacking flamenco to live past 60 days.

In future experiments, the Helfand lab plans to tryother methods of prolonging fly lifespan, forinstance by overexpressing components of thepiRNA pathway.

The biology of aging

The discovery that the piRNA pathway works in afully developed, healthy, non-reproductive bodytissue and protects health and lifespan is animportant finding, Helfand said, but it's not clear yethow far the discovery can take the biology of aging.

"We are just identifying that it is in this specifictissue, and we're leaving room for the possibilitythat it may be in other tissues in the body that arenot gonadal and this may also be the case for otheranimals as well," Jones said. "It's possible that thispathway has roles in other somatic tissues."

It's also not clear whether the piRNA pathway hassimilar effects on health in mammals and, inparticular, humans.

But in recent years Helfand and colleagues atBrown have published several papers using avariety of models, including human cells, thattogether strongly associate aging, increased TEactivity, poor health and decreased longevity. Thefindings have led them to posit a "transposontheory of aging."

Now with a $9.6 million federal grant awardedearlier this year, Helfand's close colleague JohnSedivy, professor of biology, is leading a three-year, multi-institution effort to test the theory and todetermine if interventions are possible.

More information: Nature Communications, DOI:10.1038/NCOMMS13856

Provided by Brown UniversityAPA citation: RNA pathway plays key role in health, lifespan, fly study shows (2016, December 21)retrieved 23 October 2021 from https://phys.org/news/2016-12-rna-pathway-key-role-health.html

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