Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

FISH-ing for links between cancer and aging

07.02.2007
Wielding a palette of chromosome paints, scientists at the Salk Institute for Biological Studies have taken a step closer to understanding the relationship between aging and cancer by visualizing chromosomes of cells from patients with a heritable premature aging disease known as Werner Syndrome.

In a study to be published in this week's online edition of the Proceedings of the National Academy of Sciences researchers led by Jan Karlseder, Ph.D., assistant professor in Salk's Regulatory Biology Laboratory, showed that rebuilding structures called telomeres, which are found at the tips of each chromosome, significantly blocks the type of genetic damage seen in cells of patients with Werner Syndrome.

Patients with Werner Syndrome manifest signs of aging, such as skin wrinkling, baldness, or hair graying, in their teens. Most die in their 40's or 50's due to a predisposition to diseases like cancer. "Cancer is almost always related to chromosomal instability," explains Karlseder. "If telomeres are lost on individual chromosomes, then chromosomes are not protected and can fuse with other nonprotected chromosomes. Then when cells divide, chromosomes randomly break, leading to genome instability."

The current study extended work published in 2004 by Karlseder and first author Laure Crabbe, Ph.D., who was a graduate student in the Karlseder lab at the time. In that work, the team used a technique called FISH-short for fluorescent in situ hybridization-to microscopically visualize both the telomeres and chromosomal DNA from Werner Syndrome patients. They reported that some protective telomeres were actually missing on patients' chromosomes, a finding Karlseder describes as "a fairly catastrophic event for a cell."

... more about:
»Aging »DNA »Karlseder »Syndrome »Telomere »WRN »patients

For the current study, Salk researchers grew cells from Werner Syndrome patients in tissue culture dishes and, aided by colleagues at the Institute of Human Genetics in Heidelberg, Germany, evaluated DNA damage using a highly colorful variation of the FISH technique called chromosome painting. This technique "paints" or labels every pair of the 46 chromosomes with a different colored fluorescent dye, enabling investigators to easily see breakage or fusion of chromosomes that are characteristic of damaged DNA under the microscope.

Then they artificially supplied the cultured cells with one of two genes-either a functional copy of the WRN gene, which is mutant or nonfunctional in Werner Syndrome, or a gene encoding the protein telomerase, which elongates short or missing telomeres. After cells divided several times, their DNA was reexamined for the type of damage associated with both aging and cancer.

Cells supplied with a functional WRN gene showed decreased DNA damage compared to untreated cells, which was predictable: the WRN gene encodes a protein called a helicase that unwinds tightly coiled DNA strands when cells divide. Loss of WRN protein in individuals with Werner Syndrome is responsible for the disease. Explains Crabbe, now a postdoctoral fellow at The Institute of Human Genetics in Montpellier, France, "The lack of a single protein (WRN) induced loss of some telomeres, leading to a premature cellular growth arrest."

However, the most interesting finding was what the scientists observed in cells supplied with added telomerase. "When we put telomerase into cells, we suppressed accumulation of mutations to the same degree as when we put the WRN protein back," reports Karlseder. "It fixed the defect by elongating short telomeres seen in Werner Syndrome cells."

Crabbe, who is continuing to study DNA replication as a postdoc, concludes that these findings not only provide a mechanism underlying accelerated aging seen in Werner Syndrome but establish a link to cancer predisposition, saying, "These results indicate that the telomere dysfunction in Werner Syndrome cells is a major cause of genomic instability and could explain the high incidence of cancer seen in this disease."

Translating these findings into a treatment for Werner Syndrome will be extremely difficult. However, Karlseder feels optimistic about what these investigations show. "We study this disease because it is an excellent model for aging, and we show here a direct relation between aging, telomere loss, and cancer occurrence," he says. "I predict that cancer in older people has precisely the same basis as that seen in Werner Syndrome patients. That is why this was such a satisfying study."

Gina Kirchweger | EurekAlert!
Further information:
http://www.salk.edu

Further reports about: Aging DNA Karlseder Syndrome Telomere WRN patients

More articles from Life Sciences:

nachricht Cnidarians remotely control bacteria
21.09.2017 | Christian-Albrechts-Universität zu Kiel

nachricht Immune cells may heal bleeding brain after strokes
21.09.2017 | NIH/National Institute of Neurological Disorders and Stroke

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

Im Focus: Fast, convenient & standardized: New lab innovation for automated tissue engineering & drug

MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems Holding GmbH about commercial use of a multi-well tissue plate for automated and reliable tissue engineering & drug testing.

MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Comet or asteroid? Hubble discovers that a unique object is a binary

21.09.2017 | Physics and Astronomy

Cnidarians remotely control bacteria

21.09.2017 | Life Sciences

Monitoring the heart's mitochondria to predict cardiac arrest?

21.09.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>