Stem cells and precursor cells can proliferate to repopulate damaged tissues. During aging, however, these cells lose their ability to divide—a process that is called senescence.
Now, a team of researchers led by Toru Kondo at the RIKEN Center for Developmental Biology, Kobe, has identified esophageal cancer-related gene 4 (Ecrg4) as being responsible for senescence of precursor cells in the central nervous system during aging1. This finding could explain why neurodegenerative diseases, such as Alzheimer's disease, are prevalent in elderly individuals.
Addition of serum to oligodendrocyte precursor cells (OPCs) in culture drives them toward a senescent phenotype, making them an ideal model system to study genes that induce senescence. Kondo and colleagues looked at changes in gene expression during induction of senescence in mouse OPCs and found that the expression of Ecrg4 increased the most in senescent OPCs.
When the researchers overexpressed Ecrg4 in rat OPCs, this arrested the cell cycle, and increased the proportion of cells that were labeled by a marker of cell senescence. The protein Ecrg4 seemed to act by inducing the degradation of proteins called cyclins, which drive cell cycle progression. When they reduced Ecrg4 expression, it blocked the induction of OPC senescence that is normally induced by serum.
In the culture medium of OPCs that were already senescent, Kondo and colleagues found that Ecrg4 protein was present. Administering recombinant Ecrg4 protein onto OPCs in culture also induced senescence, suggesting that Ecrg4 is a secreted protein that drives OPC senescence.
They also observed that Ecrg4 was highly expressed in the brains of old—but not young—mice, in brain regions rich with neural precursor cells and OPCs. Further, they found that the cells expressing Ecrg4 in the aging brain were not proliferating. In fact, Ecrg4-expressing cells in the aging brain seemed to be senescent, since they were co-labeled with a senescence marker. “An important next step in this research,” says Kondo, “is to make Ecrg4 knockout mice to examine the functions of Ecrg4 in vivo.”
Identifying factors that drive neural precursor cell senescence may one day lead to therapies that can kick-start their proliferation that has stalled during aging, which could help restore neuronal loss in diseases such as stroke or Parkinson's disease. “Our findings provide a new clue to investigate the mechanism of brain aging,” explains Kondo, “and may lead to the development of new methods to prevent aging and age-related diseases.”
The corresponding author for this highlight is based at the Laboratory for Cell Lineage Modulation, RIKEN Center for Developmental Biology
Kujuro, Y., Suzuki, N. & Kondo, T. Esophageal cancer-related gene 4 is a secreted inducer of cell senescence expressed by aged CNS precursor cells. Proceedings of the National Academy of Science USA 107, 8259–8264 (2010)
gro-pr | Research asia research news
Seeking structure with metagenome sequences
20.01.2017 | DOE/Joint Genome Institute
Snap, Digest, Respire
20.01.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau
An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
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...
19.01.2017 | Event News
10.01.2017 | Event News
09.01.2017 | Event News
20.01.2017 | Life Sciences
20.01.2017 | Physics and Astronomy
20.01.2017 | Materials Sciences