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 Reptile vocalization is surprisingly flexible
30.05.2017 | Max-Planck-Institut für Ornithologie

nachricht New photocatalyst speeds up the conversion of carbon dioxide into chemical resources
29.05.2017 | DGIST (Daegu Gyeongbuk Institute of Science and Technology)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Strathclyde-led research develops world's highest gain high-power laser amplifier

The world's highest gain high power laser amplifier - by many orders of magnitude - has been developed in research led at the University of Strathclyde.

The researchers demonstrated the feasibility of using plasma to amplify short laser pulses of picojoule-level energy up to 100 millijoules, which is a 'gain'...

Im Focus: Can the immune system be boosted against Staphylococcus aureus by delivery of messenger RNA?

Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.

Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

Reptile vocalization is surprisingly flexible

30.05.2017 | Life Sciences

EU research project DEMETER strives for innovation in enzyme production technology

30.05.2017 | Power and Electrical Engineering

New insights into the ancestors of all complex life

29.05.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>