Navigation Links
Why the biological clock? Penn study says aging reduces centromere cohesion, disrupts reproduction
Date:9/8/2010

PHILADELPHIA - 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.


'/>"/>

Contact: Jordan Reese
jreese@upenn.edu
215-573-6604
University of Pennsylvania
Source:Eurekalert  

Related biology news :

1. Biological sand filters, a practical approach to combat poverty and inequality
2. Argonne scientists peer into heart of compound that may detect chemical, biological weapons
3. GEN reports on novel tools for deciphering biological networks
4. Animal and biological science highlights: San Antonio Fluid Dynamics Conference, Nov. 23-25
5. Argonne scientists discover possible mechanism for creating handedness in biological molecules
6. Study finds most wars occur in Earths richest biological regions
7. Biological control of tropical weeds using arthropods
8. Musicians have biological advantage in identifying emotion in sound
9. Unclear regulations obstacle to biological diversity
10. New explanation for a puzzling biological divide along the Malay Peninsula
11. CEL-SCI Corporation to Launch Aseptic Filling for Stem Cell Produced Therapies and Other Biological Products
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Why the biological clock? Penn study says aging reduces centromere cohesion, disrupts reproduction
(Date:6/21/2016)... British Columbia , June 21, 2016 /PRNewswire/ ... appointed to the new role of principal product ... been named the director of customer development. Both ... NuData,s chief technical officer. The moves reflect NuData,s ... teams in response to high customer demand and ...
(Date:6/9/2016)... , June 9, 2016  Perkotek an innovation leader in attendance control systems is ... log work hours, for employers to make sure the right employees are actually signing ... http://photos.prnewswire.com/prnh/20160609/377486LOGO ... ... ...
(Date:6/2/2016)... The Department of Transport Management (DOTM) ... million US Dollar project, for the , Supply ... Enrolment, and IT Infrastructure , to ... implementation of Identity Management Solutions. Numerous renowned international vendors participated ... was selected for the most compliant and innovative ...
Breaking Biology News(10 mins):
(Date:6/24/2016)... ... June 24, 2016 , ... Researchers at the Universita ... miRNAs in people with peritoneal or pleural mesothelioma. Their findings are the subject of ... now. , Diagnostic biomarkers are signposts in the blood, lung fluid or tissue ...
(Date:6/23/2016)... 2016 /PRNewswire/ - FACIT has announced the creation ... biotechnology company, Propellon Therapeutics Inc. ("Propellon" or "the ... a portfolio of first-in-class WDR5 inhibitors for the ... WDR5 represent an exciting class of therapies, possessing ... for cancer patients. Substantial advances have been achieved ...
(Date:6/23/2016)... 2016  The Prostate Cancer Foundation (PCF) is pleased to announce ... cures for prostate cancer. Members of the Class of 2016 were selected from ... Read More About the Class of 2016 PCF Young Investigators ... ... ...
(Date:6/23/2016)... ... 23, 2016 , ... STACS DNA Inc., the sample tracking software company, today ... Laboratory, has joined STACS DNA as a Field Application Specialist. , “I am ... and COO of STACS DNA. “In further expanding our capacity as a scientific integrator, ...
Breaking Biology Technology: