These authors made equal contributions to the manuscript.
Identification of evolutionarily conserved genetic regulators of cellular aging
Article first published online: 28 OCT 2010
© 2010 The Authors. Aging Cell © 2010 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland
Volume 9, Issue 6, pages 1084–1097, December 2010
How to Cite
Laschober, G. T., Ruli, D., Hofer, E., Muck, C., Carmona-Gutierrez, D., Ring, J., Hutter, E., Ruckenstuhl, C., Micutkova, L., Brunauer, R., Jamnig, A., Trimmel, D., Herndler-Brandstetter, D., Brunner, S., Zenzmaier, C., Sampson, N., Breitenbach, M., Fröhlich, K.-U., Grubeck-Loebenstein, B., Berger, P., Wieser, M., Grillari-Voglauer, R., Thallinger, G. G., Grillari, J., Trajanoski, Z., Madeo, F., Lepperdinger, G. and Jansen-Dürr, P. (2010), Identification of evolutionarily conserved genetic regulators of cellular aging. Aging Cell, 9: 1084–1097. doi: 10.1111/j.1474-9726.2010.00637.x
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- Issue published online: 10 NOV 2010
- Article first published online: 28 OCT 2010
- Accepted manuscript online: 30 SEP 2010 10:08AM EST
- Acceptance for publication 14 September 2010
- replicative lifespan;
- replicative senescence;
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.