title: Identification of evolutionarily conserved genetic regulators of cellular aging.
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.
authors.affiliation: Institute for Biomedical Aging Research, Austrian Academy of Sciences, Rennweg 10, A-6020 Innsbruck, Austria.
authors.forename: Gerhard T
authors.initials: GT
authors.lastname: Laschober
authors.forename: Doris
authors.initials: D
authors.lastname: Ruli
authors.forename: Edith
authors.initials: E
authors.lastname: Hofer
authors.forename: Christoph
authors.initials: C
authors.lastname: Muck
authors.forename: Didac
authors.initials: D
authors.lastname: Carmona-Gutierrez
authors.forename: Julia
authors.initials: J
authors.lastname: Ring
authors.forename: Eveline
authors.initials: E
authors.lastname: Hutter
authors.forename: Christoph
authors.initials: C
authors.lastname: Ruckenstuhl
authors.forename: Lucia
authors.initials: L
authors.lastname: Micutkova
authors.forename: Regina
authors.initials: R
authors.lastname: Brunauer
authors.forename: Angelika
authors.initials: A
authors.lastname: Jamnig
authors.forename: Daniela
authors.initials: D
authors.lastname: Trimmel
authors.forename: Dietmar
authors.initials: D
authors.lastname: Herndler-Brandstetter
authors.forename: Stefan
authors.initials: S
authors.lastname: Brunner
authors.forename: Christoph
authors.initials: C
authors.lastname: Zenzmaier
authors.forename: Natalie
authors.initials: N
authors.lastname: Sampson
authors.forename: Michael
authors.initials: M
authors.lastname: Breitenbach
authors.forename: Kai-Uwe
authors.initials: KU
authors.lastname: Fröhlich
authors.forename: Beatrix
authors.initials: B
authors.lastname: Grubeck-Loebenstein
authors.forename: Peter
authors.initials: P
authors.lastname: Berger
authors.forename: Matthias
authors.initials: M
authors.lastname: Wieser
authors.forename: Regina
authors.initials: R
authors.lastname: Grillari-Voglauer
authors.forename: Gerhard G
authors.initials: GG
authors.lastname: Thallinger
authors.forename: Johannes
authors.initials: J
authors.lastname: Grillari
authors.forename: Zlatko
authors.initials: Z
authors.lastname: Trajanoski
authors.forename: Frank
authors.initials: F
authors.lastname: Madeo
authors.forename: Günter
authors.initials: G
authors.lastname: Lepperdinger
authors.forename: Pidder
authors.initials: P
authors.lastname: Jansen-Dürr
mesh_terms: D000328:Adult; D016922:Cellular Senescence / Q000235:genetics*; D002675:Child, Preschool; D030541:Databases, Genetic; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D006801:Humans; D008875:Middle Aged; D018384:Oxidative Stress; D012441:Saccharomyces cerevisiae / Q000235:genetics