Corporate Banner
Satellite Banner
Scientific Community
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 2,600+ scientific posters on ePosters
  • More than 3,800+ 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

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
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
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
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
Newly Found CLAMP Protein Regulates Genes
Protein turns out to be the missing link that allows a key regulatory complex to find and operate on the lone X chromosome of male fruit flies.
Tuesday, July 23, 2013
When the Cell’s Two Genomes Collide
Animal cells contain two genomes: one in the nucleus and one in the mitochondria. When mutations occur in each, they can become incompatible, leading to disease.
Friday, February 08, 2013
Will a Genetic Mutation Cause Trouble? Ask Spliceman
New, free Web-based software described in the journal Bioinformatics analyzes DNA sequences to determine if mutations are likely to cause errors in splicing of messenger RNA.
Wednesday, March 07, 2012
Brown Researchers Create Novel Technique to Sequence Human Genome
Physicists report in the journal Nanotechnology the first experiment to move a DNA chain through a nanopore using magnets.
Thursday, April 30, 2009
Scientific News
Researchers Develop Classification Model for Cancers Caused by KRAS
Most frequently mutated cancer gene help oncologists choose more effective cancer therapies.
Chromosomal Chaos
Penn study forms basis for future precision medicine approaches for Sezary syndrome
Shaking Up the Foundations of Epigenetics
Researchers at the Centre for Genomic Regulation (CRG) and the University of Barcelona (UB) published a study that challenges some of the current beliefs about epigenetics.
Genetic Defences of Bacteria Don’t Aid Antibiotic Resistance
Genetic responses to the stresses caused by antibiotics don’t help bacteria to evolve a resistance to the medications, according to a new study by Oxford University researchers.
Tolerant Immune System Increases Cancer Risk
Researchers have found that individuals with high immunoCRIT ratios may have an increased risk of developing certain cancers.
Developing a Gel that Mimics Human Breast for Cancer Research
Scientists at the Universities of Manchester and Nottingham have been funded to develop a gel that will match many of the biological structures of human breast tissue, to advance cancer research and reduce animal testing.
Lung Repair and Regeneration Gene Discovered
New role for hedgehog gene offers better understanding of lung disease.
3 Ways Viruses Have Changed Science for the Better
Viruses are really good at what they do, and we’ve been able to harness their skills to learn about – and potentially improve – human health in several ways.
Mixed Up Cell Transportation Key Piece of ALS and Dementia Puzzle
Researchers from the University of Toronto are one step closer to solving this incredibly complex puzzle, offering hope for treatment.
New Gene Therapy for Vision Loss From a Mitochondrial Disease
NIH-funded study shows success in targeting mitochondrial DNA in mice.
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
2,600+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,800+ scientific videos