Corporate Banner
Satellite Banner
Scientific Communities
Become a Member | Sign in
Home>News>This Article

Aging Cells Lose their Grip on DNA Rogues

Published: Tuesday, February 05, 2013
Last Updated: Tuesday, February 05, 2013
Bookmark and Share
Cells lose ability to control and defend themselves against transposable elements.

Transposable elements are mobile strands of DNA that insert themselves into chromosomes with mostly harmful consequences. Cells try to keep them locked down, but in a new study, Brown University researchers report that aging cells lose their ability to maintain this control. The result may be a further decline in the health of senescent cells and of the aging bodies they compose.

Even in our DNA there is no refuge from rogues that prey on the elderly. Parasitic strands of genetic material called transposable elements — transposons — lurk in our chromosomes, poised to wreak genomic havoc. Cells have evolved ways to defend themselves, but in a new study, Brown University researchers describe how cells lose this ability as they age, possibly resulting in a decline in their function and health.

Barbara McClintock, awarded the Nobel Prize in 1983, made the original discovery of transposons in maize. Since then scientists have found cases in which the chaos they bring can have long-term benefits by increasing genetic diversity in organisms, but in most cases the chaos degrades cell function, such as by disrupting useful genes.

“The cell really is trying to keep these things quiet and keep these things repressed in its genome,” said John Sedivy, professor of medical science in the Department of Molecular Biology, Cell Biology, and Biochemistry and senior author of the new study published online in the journal Aging Cell. “We seem to be barely winning this high-stakes warfare, given that these molecular parasites make up over 40 percent of our genomes.”

Cells try to clamp down on transposons by winding and packing transposon-rich regions of the genome around little balls of protein called nucleosomes. This confining arrangement is called heterochromatin, and the DNA that is trapped in such a tight heterochromatin prison cannot be transcribed and expressed.

What the research revealed, however, is that carefully maintaining a heterochromatin prison system is a younger cell’s game.

“It’s very clear that chromatin changes profoundly with aging,” Sedivy said.

What Sedivy, lead author Marco De Cecco, and their co-authors measured in several experiments was that young and spry cells distinctly maintain open “euchromatin” formations in regions where essential genes are located and closed “heterochromatin” formations around areas with active transposable elements and few desirable genes.

The distinction appeared to become worn in aging, or senescent, cells. In the observations, the chromatin that once was open tended to become more closed and the chromatin that was once closed, tended to become more open.

Working with computational biologist Nicola Neretti, assistant professor of biology, Sedivy and De Cecco conducted a genome-wide analysis of these differences. The team extracted and then sequenced DNA from young and senescent human fibroblast cells using a technique called FAIRE. Essentially FAIRE uses chemicals such as formaldehyde to separate out DNA that is loosely packed in euchromatin from DNA that is more tightly wound up in heterochromatin.

Then the scientists compared the DNA that was coming from open or closed chromatin formations in the young and senescent cells.

“Given that our genomes contain well over a million copies of transposable elements and that they are very similar to one another, tracking all this mayhem is no easy matter,” Neretti said. "Computationally speaking, it’s a nightmare.”

But Sedivy said results were well worth the effort. In their study not only did they find that the chromatin lockdown was breaking down, but also that the newly freed transposons were taking full advantage.

“I was really surprised to see that first of all these transposable elements start to get expressed and that they actually start moving around [to other regions in the genome],” Sedivy said. “That’s really an amazing thing.”

How bad and how to stop it?

What’s not clear from the study is the relevance of the damage that the cells suffer from the transposable element jailbreak and resulting genetic crime spree. That depends on the timing, which Sedivy’s team measured only in approximate terms.

“Is the transposition really bad for the organism or is it something that happens so late that by that point the organism has already accumulated so much age-associated damage?” he asked. “Then maybe this extra insult of transposition is not going to make a lot of difference.”

The question matters, Sedivy says, because drugs might be able to suppress transposons in aging cells. Virtually all of the transposons of concern in mammals are so-called “retrotransposons” because they use RNA and an enzyme to copy themselves. Certain HIV drugs work by these enzymes called “reverse transcriptases.” Remarkably, Sedivy said, the reverse transcriptase of the major human retrotransposons called “L1” has been shown by researchers to be inhibited by some HIV drugs widely used in the clinic.

“The prospects of coming up with an existing drug therapy is something we really need to think about seriously,” he said. “We’re definitely going to test that and in the future, if needed, we also should be able to design new drugs that are highly specific for L1.”

Ultimate success would provide a way to restore order in the cells and forestall at least some of the molecular ravages of age.

In addition to Sedivy, De Cecco, and Neretti, other authors on the paper are Steven Criscione, Edward Peckham, Sara Hillenmeyer, Eliza Hamm, Jayameenakshi Manivannan, Abigail Peterson, and Jill Kreiling.

Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,800+ scientific posters on ePosters
  • More Than 4,000+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Tissue Engineers Recruit Cells to Make Their Own Strong Matrix
Extracellular matrix is the material that gives tissues their strength and stretch. It’s been hard to make well in the lab, but a Brown University team reports new success. The key was creating a culture environment that guided cells to make ECM themselves.
Tuesday, November 10, 2015
Proteins with ALS, Cancer Role Do Not Assume a Regular Shape
Our cells contain proteins, essential to functions like protein creation and DNA repair but also involved in forms of ALS and cancer, that never take a characteristic shape, a new study shows.
Monday, October 12, 2015
Study Backs Flu Vaccinations for Elderly
Brown University researchers found vaccines well matched to the year’s flu strain significantly reduce deaths and hospitalizations compared to when the match is poor, suggesting that vaccination indeed makes a difference.
Wednesday, August 26, 2015
Web App Helps Researchers Explore Cancer Genetics
Brown University computer scientists have developed a new interactive tool to help researchers and clinicians explore the genetic underpinnings of cancer.
Monday, July 27, 2015
Tapeworm Drug Shows Promise Against MRSA
A new study shows that a drug already approved to fight tapeworms in people, effectively treated MRSA superbugs in lab cultures and in infected nematode worms.
Monday, April 27, 2015
A New Wrinkle For Cell Culture
Researchers at Brown University have developed an advanced technique for cell culturing that uses sheets of wrinkled graphene to mimic the complex 3-D environment inside the body.
Friday, April 24, 2015
Gold By Special Delivery Intensifies Cancer-Killing Radiation
Researchers at Brown and URI have demonstrated what could be a more precise method for targeting cancer cells for radiation.
Wednesday, April 15, 2015
DNA ‘Cage’ Could Improve Nanopore Technology
Scientists at Brown University have designed a nanoscale cage that can trap a single DNA strand and allow before-and-after sequencing of the same DNA strand in research trials.
Wednesday, February 11, 2015
New Technology Makes Tissues, Someday Maybe Organs
A new device for building large tissues from living components of three-dimensional microtissues borrows on ideas from electronics manufacturing.
Wednesday, January 07, 2015
New Research Unlocks a Mystery of Albinism
A team led by Brown University biologists has discovered the way in which a specific genetic mutation appears to lead to the lack of melanin production underlying a form of albinism.
Thursday, December 18, 2014
If CD8 T Cells Take on One Virus, They’ll Fight Others Too
The findings suggest that innate immunity changes with the body’s experience and that the T cells are more versatile than thought.
Saturday, October 25, 2014
A ‘Clear’ Choice for Clearing 3-D Cell Cultures
A new study is the first to evaluate three chemical technologies for making animal tissues see-through side-by-side for use with engineered 3-D tissue cultures.
Thursday, September 04, 2014
Study Proposes New Ovarian Cancer Targets
Researchers from Brown University propose that TAFs may be important suspects in the progression of ovarian cancer.
Friday, March 14, 2014
Gold Nanoparticles Give an Edge in Recycling CO2
It’s a 21st-century alchemist’s dream: turning Earth’s superabundance of carbon dioxide into fuel or useful industrial chemicals.
Monday, November 11, 2013
Fly Study Finds Two New Drivers of RNA Editing
A new study in Nature Communications finds that RNA editing is not only regulated by sequences and structures near the editing sites but also by ones found much farther away.
Thursday, August 08, 2013
Scientific News
High Throughput Mass Spectrometry-Based Screening Assay Trends
Dr John Comley provides an insight into HT MS-based screening with a focus on future user requirements and preferences.
How a Genetic Locus Protects Adult Blood-Forming Stem Cells
Mammalian imprinted Gtl2 protects adult hematopoietic stem cells by restricting metabolic activity in the cells' mitochondria.
Genetic Basis of Fatal Flu Side Effect Discovered
A group of people with fatal H1N1 flu died after their viral infections triggered a deadly hyperinflammatory disorder in susceptible individuals with gene mutations linked to the overactive immune response, according to a recent study.
New Tech Vastly Improves CRISPR/Cas9 Accuracy
A new CRISPR/Cas9 technology developed by scientists at UMass Medical School is precise enough to surgically edit DNA at nearly any genomic location, while avoiding potentially harmful off-target changes typically seen in standard CRISPR gene editing techniques.
The MaxSignal Colistin ELISA Test Kit from Bioo Scientific
Kit can help prevent the antibiotic apocalypse by keeping last resort drugs out of the food supply.
"Good" Mozzie Virus Might Hold Key to Fighting Human Disease
Australian scientists have discovered a new virus carried by one of the country’s most common pest mosquitoes.
Non-Disease Proteins Kill Brain Cells
Scientists at the forefront of cutting-edge research into neurodegenerative diseases such as Alzheimer’s and Parkinson’s have shown that the mere presence of protein aggregates may be as important as their form and identity in inducing cell death in brain tissue.
Closing the Loop on an HIV Escape Mechanism
Research team finds that protein motions regulate virus infectivity.
New Class of RNA Tumor Suppressors Identified
Two short, “housekeeping” RNA molecules block cancer growth by binding to an important cancer-associated protein called KRAS. More than a quarter of all human cancers are missing these RNAs.
Potential Treatment for Life-Threatening Viral Infections Revealed
The findings point to new therapies for Dengue, West Nile and Ebola.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,800+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,000+ scientific videos