Due to a loss of functionality in hematopoietic stem cells, immune defects occur during aging. Now, researchers from Leibniz Institute on Aging – Fritz Lipmann Institute (FLI) in Jena, Germany, identified gene Per2, whose deletion leads to a stabilization of the number of immune cells in the blood of aged mice and prolongs their lifespan. Results are published online in Journal Nature Cell Biology on April 18, 2016.
There’s no other age group suffering more from infectious diseases than seniors. With growing age, the risk of chronic and cute infections increases. This is due to the diminishing potential of hematopoietic stem cells (HSC) to build blood and immune cells in an appropriate number.
In particular, HSC’s capability to build lymphocytes is strongly declining, which leads to imbalances in blood cell composition and, thus, to immune defects limiting overall fitness and organismal survival during aging. There is experimental evidence that the accumulation of DNA damage contributes to these aging-induced immune impairments.
Now, a group of researchers lead by Karl Lenhard Rudolph, Scientific Director of Leibniz Institute on Aging – Fritz Lipmann Institute (FLI), identified gene “Per2” as a genetic switch for a better immune system in mice: Per2 gene deletion ameliorates DNA damage responses in HSC leading to stabilization of hematopoietic stem and progenitor cells in aging mice. Hence, mice were less prone to infections and exhibited an elongated lifespan by 15 % without increases in cancer. The results of the study are published online on April 18, 2016, in Journal Nature Cell Biology.
“Circadian Clock“-gene Per2 identified by a genetic screen
For their study, in vivo RNA-mediated interference (RNAi) screenings were conducted in mice. 459 putative tumor suppressor genes were targeted to identify genes that limit the self-renewal capacity of HSC in response to DNA damage and aging. This screen identified “period circadian clock 2 (Per2)”-gene – usually one out of various genes regulating sleep-wake cycle – to represent a major factor limiting the maintenance and repopulation capacity of HSC in the context of various types of DNA damage and aging.
Interestingly, Per2 deletion was sufficient to maintain a balanced production of lymphocytes, and hence, to improved immune function in aging mice. A similar effect was also found for DNA damages caused by the shortening of telomeres – the protective caps at our chromosomes’ ends –, a mechanism though to be relevant for human aging.
A further step towards healthy aging
“All in all, these results are very promising, but equally surprising”, K. Lenhard Rudolph summarizes. “We did not expect such a strong connection between switching off a single gene and improving the immune system so clearly”. It will be of future interest to study if the results are transferable to humans. Although humans and mice are genetically quite similar, genes usually regulate myriad of processes in an organism, and possible side-effects of Per2 deletion will have to be elucidated very carefully.
Interestingly, Per2 gene mutations in humans have been associated with advanced sleep disorders leading to advanced tiredness of the patients in the early evening hours. “It is not yet clear whether this mutation in humans would have a benefit such as improved immune functions in aging – it is of great interest for us to further investigate this” Rudolph says.
Wang J, Morita Y, Han B, Niemann S, Löer B, Rudolph KL.
Per2 induction limits lymphoid-biased haematopoietic stem cells and lymphopoiesis in the context of DNA damage and ageing.
Nature Cell Biology 2016 (e-pub ahead of print), DOI: 10.1038/ncb3342.
Dr. Evelyn Kästner
Leibniz Institute on Aging – Fritz Lipmann Institute (FLI), Beutenbergstr. 11, D-07745 Jena
Tel.: + 49 3641-656373, E-Mail: firstname.lastname@example.org
The Leibniz Institute on Aging – Fritz Lipmann Institute (FLI) is the first German research organization dedicated to biomedical aging research since 2004. More than 330 members from over 30 nations explore the molecular mechanisms underlying aging processes and age-associated diseases. For more information, please visit http://www.leibniz-fli.de.
The Leibniz Association connects 88 independent research institutions that range in focus from the natural, engineering and environmental sciences via economics, spatial and social sciences to the humanities. Leibniz Institutes address issues of social, economic and ecological relevance. They conduct knowledge-driven and applied basic research, maintain scientific infrastructure and provide research-based services. The Leibniz Association identifies focus areas for knowledge transfer to policy-makers, academia, business and the public. Leibniz Institutes collaborate intensively with universities – in the form of “WissenschaftsCampi” (thematic partnerships between university and non-university research institutes), for example – as well as with industry and other partners at home and abroad. They are subject to an independent evaluation procedure that is unparalleled in its transparency. Due to the institutes’ importance for the country as a whole, they are funded jointly by the Federation and the Länder, employing some 18,100 individuals, including 9,200 researchers. The entire budget of all the institutes is approximately 1.64 billion EUR. See http://www.leibniz-association.eu for more information.
http://www.leibniz-fli.de - Website Leibniz Institute on Aging - Fritz Lipmann Institute (FLI)
Dr. Kerstin Wagner | idw - Informationsdienst Wissenschaft
The interactome of infected neural cells reveals new therapeutic targets for Zika
23.01.2017 | D'Or Institute for Research and Education
Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery
20.01.2017 | GSI Helmholtzzentrum für Schwerionenforschung GmbH
For the first time ever, a cloud of ultra-cold atoms has been successfully created in space on board of a sounding rocket. The MAIUS mission demonstrates that quantum optical sensors can be operated even in harsh environments like space – a prerequi-site for finding answers to the most challenging questions of fundamental physics and an important innovation driver for everyday applications.
According to Albert Einstein's Equivalence Principle, all bodies are accelerated at the same rate by the Earth's gravity, regardless of their properties. This...
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...
19.01.2017 | Event News
10.01.2017 | Event News
09.01.2017 | Event News
23.01.2017 | Process Engineering
23.01.2017 | Physics and Astronomy
23.01.2017 | Life Sciences