Neuroscientists show 'jumping genes' may contribute to aging-related brain defects

April 8, 2013

As the body ages, the physical effects are notable; wrinkles in the skin appear, physical exertion becomes harder. But there are also less visible processes going on. Inside aging brains there is another phenomenon at work, which may contribute to age-related brain defects.

In a paper published in the journal Nature Neuroscience CSHL Associate Professor Joshua Dubnau and colleagues show that so-called "jumping genes," or transposons, increase in abundance and activity in the brains of fruit flies as they age.

Originally discovered at CSHL by Professor Barbara McClintock while working on maize (corn) in the 1940s, transposons are typically repeat that insert themselves into the DNA of an animal or plant.

The moniker "" comes from the fact that when activated they can reinsert themselves, or transpose, into another part of the genome. In the course of doing so they are thought to either provide variations in genetic function or, especially in the , induce potentially fatal disruptive defects.

Jumping genes in the brains of fruit flies

The of a fruit fly can be measured in days. The average fly lives for somewhere between 40-50 days. But they provide a powerful model with which to get at the genetics of things like aging and , including memory.

Dubnau's interest was piqued by an experiment in which his team showed that when the activity of a protein called Ago2 (Argonaute 2) was perturbed, so was —which was tested using a trained Pavolvian response to smell. "This is a neurodegenerative defect that gets profoundly more apparent with age of the flies," notes Dubnau.

Since Ago2 is known to be involved in protecting against transposon activity in fruit flies, Dubnau and colleagues in his lab, including Wanhe Li and Lisa Prazak, were compelled to look for transposons.

Though transposons have been shown to be active during normal brain development, they are silenced soon afterward. The implication is that they have some functional role in development.

When Dubnau's group looked for transposons they found that there is a marked increase in transposon levels in the brain cells, or neurons, by 21 days of age in normal fruit flies. The levels were observed to increase steadily with age. These transposons, including one in particular called gypsy, were highly active, jumping from place to place in the .

When they blocked Ago2 from being expressed in fruit flies, transposons accumulated at a much younger age. In fact the levels of transposons in young Ago2 "knock-out" flies were equivalent to those in much older normal flies, and increased further still as the Ago2 knock-out flies aged.

Accompanying this transposon accumulation were defects in long-term memory that mirrored those usually seen in much older flies, as well as a much-reduced lifespan. "Essentially the Ago2 knock out flies have no long-term memory by the time they are 20 days old, while normal flies have a normal long-term memory at the same age," Dubnau reports.

In a previous paper the Dubnau lab, in collaboration with CSHL Assistant Professor Molly Hammell, established a connection between transposons and devastating neurodegenerative diseases such ALS (amyotrophic lateral sclerosis, or Lou Gehrig's disease) and FTLD (frontotemporal lobar degeneration). The link was the protein TDP-43, which they showed controls transposon activity.

Taken together with the results in his team's new paper, Dubnau proposes that a "transposon storm" may be responsible for age-related neurodegeneration as well as the pathology seen in some neurodegenerative disorders.

However, his studies so far don't address whether transposons are the cause or an effect of aging-related . "The next step will be to activate transposons by genetically manipulating and ask whether they are a direct cause of neurodegeneration," Dubnau says.

Explore further: Scientists shed light on age-related memory loss and possible treatments

More information: "Activation of transposable elements during aging and neuronal decline in Drosophila" is published online in Nature Neuroscience on April 7, 2013. The authors are: Wanhe Li1, Lisa Prazak, Nabanita Chatterjee, Servan Grüninger, Lisa Krug, Delphine Theodorou & Josh Dubnau. The paper can be obtained online at doi:10.1038/nn.3368

Related Stories

Recommended for you

New insights on how cocaine changes the brain

November 25, 2015

The burst of energy and hyperactivity that comes with a cocaine high is a rather accurate reflection of what's going on in the brain of its users, finds a study published November 25 in Cell Reports. Through experiments conducted ...

Can physical exercise enhance long-term memory?

November 25, 2015

Exercise can enhance the development of new brain cells in the adult brain, a process called adult neurogenesis. These newborn brain cells play an important role in learning and memory. A new study has determined that mice ...

Umbilical cells help eye's neurons connect

November 24, 2015

Cells isolated from human umbilical cord tissue have been shown to produce molecules that help retinal neurons from the eyes of rats grow, connect and survive, according to Duke University researchers working with Janssen ...

Brain connections predict how well you can pay attention

November 24, 2015

During a 1959 television appearance, Jack Kerouac was asked how long it took him to write his novel On The Road. His response – three weeks – amazed the interviewer and ignited an enduring myth that the book was composed ...

No cable spaghetti in the brain

November 24, 2015

Our brain is a mysterious machine. Billions of nerve cells are connected such that they store information as efficiently as books are stored in a well-organized library. To this date, many details remain unclear, for instance ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.