Do Rogue Transposons Contribute To Aging?

 Credit: Phillip Dumesic, UCSF (Adapted from Transposon by Lauren Solomon, Broad Institute

As genomes become more unstable with age, uncaged transposons may cause chaos and contribute to the aging process

Transposons are sequences of DNA that can jump and integrate in another location - disrupting surrounding genes. Once believed to be 'junk DNA', Scientists are still attempting to understand exactly what transposons do, but we know they've played an important role in evolution; jumping around to form new genes and alter regulation. They may also play a role in embryonic development too. 

Let loose

A number of things appear to happen to the genome as organisms age, and one of them is a progressive loosening of DNA in many areas. DNA is normally tightly wound up in a form called heterochromatin, but in older cells heterochromatin appears to relax and open up areas of the genome that were once wrapped up. This makes DNA easier to mutate, but it also turns many genes on that aren't necessarily supposed to be; causing dysregulation and interfering a finely balanced system. This gradual unravelling of DNA also has another consequence - the unveiling of transposons. 

Transposons sequences can hop to another region of the genome and integrate

"In this report the big step forward is towards the possibility of a true causal relationship. So far there have been associations and suggestions that to all of us make sense, but the difference in science is that you need the data to back up your opinion"

Rising chaos

In a new set of experiments researchers have determined that in fruit flies transposon activity takes off after a specific age in a sudden cascade that correlates with the time of death. In order to do this they inserted markers that would produce a green glow when transposons were active; enabling them to observe increasing activity in flies as they aged. 

Transposons were first discovered in corn, where they cause varied expression of colour

When the same team manipulated genes known to protect and form heterochromatin such as Su(var)3-9 (of which a similar variant exists in humans), they were able to extend life span from 60 to 80 days. Increasing expression of Dicer-2 also significantly extended lifespan, by suppressing transposon activity. 

Part of the story

Calorie restriction seemed to slow the rise of transposon activity, but an HIV drug called 3TC was also able to improve life span in flies with repressed Dicer-2 activity. It seems likely that transposon activity is part of a wider story, in which cells lose their tight control over gene expression. Exposed DNA sets the stage for cancerous mutations, chaotic gene expression and widespread dysfunction. Transposons are likely a disruptive element within an assortment of damaging changes going on, and tackling them may yield therapeutic results. 

"We're starting to put the flesh on the skeleton. There are lots of potential mechanisms that influence the aging process. We think this is one of them."

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