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IBA Publikation


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Verlag der Österreichischen Akademie der Wissenschaften
Austrian Academy of Sciences Press
A-1011 Wien, Dr. Ignaz Seipel-Platz 2,
Tel. +43-1-515 81/DW 3420, Fax +43-1-515 81/DW 3400
https://verlag.oeaw.ac.at, e-mail: bestellung.verlag@oeaw.ac.at
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IBA Publikation

Identification of evolutionarily conserved genetic regulators of cellular aging

    Gerhard T. Laschober, Doris Ruli, Edith Hofer, Christoph Muck, Didac Carmona-Gutierrez, Julia Ring, Eveline Hutter, Christoph Ruckenstuhl, Lucia Micutkova, Regina Brunauer, Angelika Jamnig, Daniela Trimmel, Dietmar Herndler-Brandstetter, Stefan Brunner, Christoph Zenzmaier, Natalie Sampson, Michael Breitenbach, Kai-Uwe Fröhlich, Beatrix Grubeck-Loebenstein, Peter Berger, Matthias Wieser, Regina Grillari-Voglauer, Gerhard G. Thallinger, Johannes Grillari, Zlatko Trajanoski, Frank Madeo, Günter Lepperdinger, Pidder Jansen-Dürr

IBA Publikation, pp. 1084-1097, 2010/10/28

doi: 10.1111/j.1474-9726.2010.00637.x


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doi:10.1111/j.1474-9726.2010.00637.x

Abstract

To identify new genetic regulators of cellular aging and senescence, we performed genome-wide comparative RNA profiling with selected human cellular model systems, reflecting replicative senescence, stress-induced premature senescence, and distinct other forms of cellular aging. Gene expression profiles were measured, analyzed, and entered into a newly generated database referred to as the GiSAO database. Bioinformatic analysis revealed a set of new candidate genes, conserved across the majority of the cellular aging models, which were so far not associated with cellular aging, and highlighted several new pathways that potentially play a role in cellular aging. Several candidate genes obtained through this analysis have been confirmed by functional experiments, thereby validating the experimental approach. The effect of genetic deletion on chronological lifespan in yeast was assessed for 93 genes where (i) functional homologues were found in the yeast genome and (ii) the deletion strain was viable. We identified several genes whose deletion led to significant changes of chronological lifespan in yeast, featuring both lifespan shortening and lifespan extension. In conclusion, an unbiased screen across species uncovered several so far unrecognized molecular pathways for cellular aging that are conserved in evolution.

Keywords: aging evolution replicative-lifespan replicative-senescence senescence yeast