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

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 2,500+ scientific posters on ePosters
  • More Than 3,700+ 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 TechnologyNetworks.com 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

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
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
NMR Advance Brings Proteins into the Open
A key protein interaction had eluded scientists’ observation until a team of researchers cracked the case by combining data from four different techniques of NMR.
Wednesday, June 26, 2013
Scientific News
The Changing Tides of the In Vitro Diagnostics Market
With the increasing focus in personalized medicine, diagnostics plays a crucial role in patient monitoring.
Immunotherapy Agent Benefits Patients with Drug-Resistant Multiple Myeloma in First Human Trial
Daratumumab proved generally safe in patients, even at the highest doses.
Low-level Arsenic Exposure Before Birth Associated with Early Puberty in Female Mice
Study examine whether low-dose arsenic exposure could have similar health outcomes in humans.
Inciting an Immune Attack On Cancer Cells
A new minimally invasive vaccine that combines cancer cells and immune-enhancing factors could be used clinically to launch a destructive attack on tumors.
‘Mutation-Tracking’ Blood Test for Breast Cancer
Scientists have developed a blood test for breast cancer able to identify which patients will suffer a relapse after treatment, months before tumours are visible on hospital scans.
Cellular Contamination Pathway for Heavy Elements Identified
Berkeley Lab scientists find that an iron-binding protein can transport actinides into cells.
Intensity of Desert Storms May Affect Ocean Phytoplankton
MIT study finds phytoplankton are extremely sensitive to changing levels of desert dust.
Common ‘Heart Attack’ Blood Test May Predict Future Hypertension
Small rises in troponin levels may have value as markers for subclinical heart damage and high blood pressure.
LaVision BioTec Reports on the Neuro Research on the Human Brain After Trauma
Company reports on the work of Dr Ali Ertürk from the Institute for Stroke and Dementia Research at LMU Munich.
NIH Study Shows No Benefit of Omega-3 Supplements for Cognitive Decline
Research was published in the Journal of the American Medical Association.
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
2,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!