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!
Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.
The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
17.01.2017 | Earth Sciences
17.01.2017 | Materials Sciences
17.01.2017 | Architecture and Construction