Featured Research

from universities, journals, and other organizations

Why the biological clock? Aging reduces centromere cohesion, disrupts reproduction, biologists discover

Date:
September 9, 2010
Source:
University of Pennsylvania
Summary:
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.

Green DNA with red kinetichore protein structures increasing in separation between young mice (top) and old.
Credit: Image courtesy of University of Pennsylvania

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.

Related Articles


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.


Story Source:

The above story is based on materials provided by University of Pennsylvania. Note: Materials may be edited for content and length.


Journal Reference:

  1. Teresa Chiang, Francesca E. Duncan, Karen Schindler, Richard M. Schultz, Michael A. Lampson. Evidence that Weakened Centromere Cohesion Is a Leading Cause of Age-Related Aneuploidy in Oocytes. Current Biology, 2010; DOI: 10.1016/j.cub.2010.06.069

Cite This Page:

University of Pennsylvania. "Why the biological clock? Aging reduces centromere cohesion, disrupts reproduction, biologists discover." ScienceDaily. ScienceDaily, 9 September 2010. <www.sciencedaily.com/releases/2010/09/100908142741.htm>.
University of Pennsylvania. (2010, September 9). Why the biological clock? Aging reduces centromere cohesion, disrupts reproduction, biologists discover. ScienceDaily. Retrieved October 24, 2014 from www.sciencedaily.com/releases/2010/09/100908142741.htm
University of Pennsylvania. "Why the biological clock? Aging reduces centromere cohesion, disrupts reproduction, biologists discover." ScienceDaily. www.sciencedaily.com/releases/2010/09/100908142741.htm (accessed October 24, 2014).

Share This



More Health & Medicine News

Friday, October 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

IKEA Desk Converts From Standing to Sitting With One Button

IKEA Desk Converts From Standing to Sitting With One Button

Buzz60 (Oct. 24, 2014) IKEA is out with a new convertible desk that can convert from a sitting desk to a standing one with just the push of a button. Jen Markham explains. Video provided by Buzz60
Powered by NewsLook.com
Ebola Protective Suits Being Made in China

Ebola Protective Suits Being Made in China

AFP (Oct. 24, 2014) A factory in China is busy making Ebola protective suits for healthcare workers and others fighting the spread of the virus. Duration: 00:38 Video provided by AFP
Powered by NewsLook.com
WHO: Millions of Ebola Vaccine Doses by 2015

WHO: Millions of Ebola Vaccine Doses by 2015

AP (Oct. 24, 2014) The World Health Organization said on Friday that millions of doses of two experimental Ebola vaccines could be ready for use in 2015 and five more experimental vaccines would start being tested in March. (Oct. 24) Video provided by AP
Powered by NewsLook.com
Doctor in NYC Quarantined With Ebola

Doctor in NYC Quarantined With Ebola

AP (Oct. 24, 2014) An emergency room doctor who recently returned to the city after treating Ebola patients in West Africa has tested positive for the virus. He's quarantined in a hospital. (Oct. 24) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins