Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Why the Biological Clock? Penn Study Says Aging Reduces Centromere Cohesion, Disrupts Reproduction

09.09.2010
University of Pennsylvania biologists studying human reproduction have identified what is likely the major contributing factor to the maternal age-associated increase in aneuploidy, the term for an abnormal number of chromosomes during reproductive cell division.

Using naturally aging mouse models, researchers showed that this basic fact of reproductive life is most likely caused by weakened chromosome cohesion. Older oocytes, or egg cells, have dramatically reduced amounts of a protein, REC8, that is essential for chromosomes to segregate correctly during the process that forms an egg. Mistakes in this process can create chromosomal abnormalities like Down syndrome.

Richard Schultz, associate dean for the natural sciences and the Charles and William L. Day Distinguished Professor of Biology in Penn’s School of Arts and Sciences, and Michael Lampson, assistant professor of biology, found that kinetochores — the protein structures that mark the site where a chromosome pair is split during cell division — are farther apart in eggs obtained from aged mice, resulting in reduced centromere cohesion. Because cohesion in these cells is established during fetal development, and must remain functional until meiotic resumption in adult life (up to ~50 years later in humans or 15 months in mice), defective cohesion is a good candidate for a process that might fail with increasing maternal age.

Researchers demonstrated that about 90 percent of age-related aneuploidies are best explained by weakened centromere cohesion. Together, these results show that the maternal age-associated increase in aneuploidy is often due to a failure to effectively replace cohesin proteins lost during aging.

“Despite the well understood nature of the issue — popularly called the biological clock — the molecular mechanisms that underpin this phenomenon have never been fully understood,” Schultz said. “Even now at the molecular level, there is no clear explanation for the loss of cohesion, in large part because almost nothing is known about how cohesion is normally maintained during the long prophase arrest in mammalian oocytes. Outstanding questions, such as the stability of cohesin complexes on chromosomes during arrest and whether new cohesins load and mature during the arrest, are now under investigation.”

To test whether cohesion defects led to the observed aneuploidies, scientists monitored chromosome segregation during the initial stages of separation, called the anaphase, in live mouse oocytes, counting the chromosomes in the resulting metaphase II eggs.

Researchers arrived at this hypothesis by identifying mRNAs that differed in oocytes of old and young mice, which suggested the spindle assembly checkpoint, kinetochore function and spindle assembly as processes that might become defective with age. Results of experiments addressed to test these possibilities suggested that they were unlikely causes. During these studies, however, the scientists noticed that sister kinetochores are farther apart in metaphase II eggs from older mice at 16 to 19 months of age compared to eggs from young mice of 6 to 14 weeks of age, a finding that drew their attention to explore reduced cohesion as a primary source for age-related aneuploidy.

The study, appearing in the journal Current Biology, was conducted by Schultz, Lampson, Teresa Chiang, Francesca E. Duncan and Karen Schindler of the Department of Biology in Penn’s School of Arts and Sciences.

The study was funded by the National Institutes of Health and a Searle Scholar Award to Lampson.

Jordan Reese | EurekAlert!
Further information:
http://www.upenn.edu

More articles from Life Sciences:

nachricht Staying in Shape
16.08.2018 | Max-Planck-Institut für molekulare Zellbiologie und Genetik

nachricht Chips, light and coding moves the front line in beating bacteria
16.08.2018 | Okinawa Institute of Science and Technology (OIST) Graduate University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

Im Focus: Lining up surprising behaviors of superconductor with one of the world's strongest magnets

Scientists have discovered that the electrical resistance of a copper-oxide compound depends on the magnetic field in a very unusual way -- a finding that could help direct the search for materials that can perfectly conduct electricity at room temperatur

What happens when really powerful magnets--capable of producing magnetic fields nearly two million times stronger than Earth's--are applied to materials that...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

2018 Work Research Conference

25.07.2018 | Event News

 
Latest News

Staying in Shape

16.08.2018 | Life Sciences

Diving robots find Antarctic seas exhale surprising amounts of carbon dioxide in winter

16.08.2018 | Earth Sciences

Protein droplets keep neurons at the ready and immune system in balance

16.08.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>