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
Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory
Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP
Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.
Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...
In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.
Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
09.12.2016 | Life Sciences
09.12.2016 | Ecology, The Environment and Conservation
09.12.2016 | Health and Medicine