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:3/3/2016)... Calif. , March 3, 2016  FlexTech, a ... the categories of Innovation, Research & Development, Leadership in ... Leadership. This is the 9 th year of ... group of companies and individuals from past years ... based on a pre-described set of criteria, by a ...
(Date:3/2/2016)... DUBLIN , March 2, 2016 /PRNewswire/ ... has announced the addition of the  "Global ... to their offering.  ,     (Logo: http://photos.prnewswire.com/prnh/20130307/600769) , ... sector to grow at a CAGR of ... http://www.researchandmarkets.com/research/wzwqtz/global_biometrics ) has announced the addition ...
(Date:3/1/2016)... -- (RSAC Booth #3041) – True fraud costs business $9 ... lost to false positives, where good customers are pushed ... the RSA Conference 2016, NuData Security is calling for a ... devaluing the data fraudsters have in abundance in favor ... --> --> Cheap and readily available ...
Breaking Biology News(10 mins):
(Date:5/3/2016)... Texas , May 3, 2016  Dr. ... plastic surgeon in The Woodlands, Texas ... destroys 24 percent of treated fat cells in just ... woman. Close to 90 percent of Americans report feeling ... options. Nonsurgical fat reduction procedures are a growing industry. ...
(Date:5/2/2016)... (PRWEB) , ... May 02, 2016 , ... StarNet Communications ... today announced the addition of three Secure Remote Desktop modules to its flagship X-Win32 ... desktops from Linux and Unix servers to the user’s PC over encrypted SSH. , ...
(Date:4/29/2016)... New York , April 29, 2016 /PRNewswire/ ... report published by Transparency Market Research "Separation Systems ... Size, Share, Growth, Trends, and Forecast 2015 - ... was valued at US$ 10,665.5 Mn in 2014 ... of 6.8% from 2015 to 2023 to reach ...
(Date:4/28/2016)... PUNE, India , April 28, 2016 ... PT, JT, Stirling, and Brayton Cryocoolers), Service (Technical Support, ... Application, and Geography - Global Forecast to 2022", published ... to USD 2.94 Billion by 2022, at a CAGR ... Browse 70 market data Tables and 94 Figures spread ...
Breaking Biology Technology: