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Good genes - long life?

12.12.2017

Researchers in Kiel discover new aspects of the “longevity gene” FOXO3

Back in 2009, members from the Cluster of Excellence "Inflammation at Interfaces” confirmed that FOXO3 is a “longevity gene”. In a new study, which has now been published in Nature Communications, the Kiel-based research team has been able to show, for the first time, which changes in the gene’s basic sequence contribute towards a particularly long life. However, it is not only our individual genetic architecture that determines how old we will be, but also the environmental and nutritional conditions. It seems as though FOXO3’s life prolonging effects come into being when the food supply is not too rich.

The FOXO3 gene boosts long lives in people. Researchers led by Professor Almut Nebel from the Institute of Clinical Molecular Biology (IKMB) at Kiel University proved this back in 2009 for the German population. But up to now, it has remained unknown which modifications in the FOXO3 gene result in an above-average lifetime. The experts have now been able to fill this gap in our knowledge. “Using our new data, we have been able to show that two variations in the FOXO3 gene in particular promote a long life,” said lead authors Dr Friederike Flachsbart and Dr Janina Dose from the IKMB to summarize their latest findings. “We found these modifications more frequently amongst people aged 100 years, than by those aged between 60 and 75.” In this current study, the experts not only examined Germans, but also compared their findings to data from Denmark and France. The genetic patterns of the centenarians were strikingly similar. The variations identified probably lead to longevity via increased expression of the FOXO3 gene. A similar mechanism exists in worms, flies and mice. 

However, other factors also influence the length of life, in addition to genetics. FOXO3 plays an important role in the insulin signaling pathway, for example. Here, the gene particularly reacts to nutrition-related stress, i.e. hunger or too much food. The researchers assume that the two longevity variations in FOXO3 lead to a higher expression of the gene under normal and low-nutrient conditions. “Our experimental data suggests that, for our Western eating habits today, which are characterized rather by excess than lack of food, the variants in the longevity gene are more likely to be disadvantageous,” presumes Nebel, the head of the study. Our eating habits have dramatically changed within a relatively short time frame. 

A comparison with published data from human skeletons from the Neolithic period, i.e. from around 7,000 years ago, shows an exciting trend: in that time, the two longevity variations in FOXO3 were much more common in the population than today. One possible reason for this could be the considerable change in what we eat. It was around 7,000 years ago that people in Europe started to settle and they began to eat more carbohydrates and animal protein in the form of milk or meat, for example. The two longevity variations in FOXO3 presumably became much rarer over the millennia, due to the fact that they no longer provided their carriers with a fitness or survival advantage under these changed eating habits. Next, biologist Nebel wants to analyze the impact of protein components on top of various nutrients, in cooperation with colleagues in Kiel: “We want to investigate which influence the two longevity variations have on FOXO3 activity, in interaction with nutrients such as sugar and fat.” 


Original publication: 
Flachsbart, F, Dose, J, Gentschew, L, Geismann, C, Caliebe, A, Knecht, C, Nygaard, M, Badarinarayan, N, ElSharawy, A, May, S, Luzius, A, Torres, GG, Jentzsch, M, Forster, M, Haesler, R, Pallauf, K, Lieb, W, Derbois, C, Galan, P, Drichel, D, Arlt, A, Till, A, Krause-Kyora, B, Rimbach, G, Blanché, H, Deleuze, J-F, Christiansen, L, Christensen, K, Nothnagel, M, Rosenstiel, P, Schreiber, S, Franke, A, Sebens, S and Nebel, A (2017): Identification and characterization of two functional variants in the human longevity gene FOXO3. Nature Communications, http://dx.doi.org/10.1038/s41467-017-02183-y

 

Contact: Professor Almut Nebel
Institute of Clinical Molecular Biology
E-mail: a.nebel@mucosa.de
Tel.: +49 (0)431 500-15155

 

Photos are available to download:
http://inflammation-at-interfaces.de/de/newsroom/aktuelles/Langlebigkeitsgen_ElisabethWalser.png
Lots of people wish to live long lives. This photo shows Elisabeth Walser, who was born in Munich in 1905. Photographer Andreas Labes took her portrait for the illustrated book “100 Jahre Leben” (Living for 100 years).

http://inflammation-at-interfaces.de/de/newsroom/aktuelles/Langlebigkeitsgen_ErichWalde.png
It is well known that mostly men profit from the longevity variations in FOXO3. Erich Walde was born in Halle an der Saale in 1905. He was also photographed by Andreas Labes for the illustrated book “100 Jahre Leben”.

Both photos may only be used in connection with the press topic “Good genes - long life?”
Photos and copyright: Andreas Labes

 

Further Information:
Publication from 2009 about the gene FOXO3 by Friederike Flachsbart, Almut Nebel and co-authors in Proceedings of the National Academy of Sciences of the United States of America: http://www.pnas.org/content/106/8/2700.long

Press contact:
Dr. Tebke Böschen
Telefon: +49 (0)431 880-4682, e-mail: tboeschen@uv.uni-kiel.de 
Website: www.inflammation-at-interfaces.de
Twitter: I@I @medinflame


The Cluster of Excellence "Inflammation at Interfaces" has been funded since 2007 by the Excellence Initiative of the German Government and the federal states with a total budget of 68 million Euros. It is currently in its second phase of funding. Around 300 cluster members are spread across the four locations: Kiel (Kiel University, University Medical Center Schleswig-Holstein (UKSH)), Lübeck (University of Lübeck, UKSH), Plön (Max Planck Institute for Evolutionary Biology) and Borstel (Research Center Borstel (FZB) – Center for Medicine and Biosciences) and are researching an innovative, systematic approach to the phenomenon of inflammation, which can affect all barrier organs such as the intestines, lungs and skin.

Cluster of Excellence Inflammation at Interfaces
Scientific Office, Management: Dr. habil. Susanne Holstein
Address: Christian-Albrechts-Platz 4, 24118 Kiel, Germany
Phone: +49 431 880-4850, Fax: +49 431 880-4894
e-mail: spetermann@uv.uni-kiel.de
Twitter: I@I @medinflame

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Dr. Tebke Böschen

press and communication

Cluster Office
Kiel University (CAU)
Christian-Albrechts-Platz 4
24118 Kiel
Germany

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Internet: www.inflammation-at-interfaces.de