Identification of evolutionarily conserved genetic regulators of cellular aging.
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.
Laschober
Gerhard T
GT
Institute for Biomedical Aging Research, Austrian Academy of Sciences, Rennweg 10, A-6020 Innsbruck, Austria.
Ruli
Doris
D
Hofer
Edith
E
Muck
Christoph
C
Carmona-Gutierrez
Didac
D
Ring
Julia
J
Hutter
Eveline
E
Ruckenstuhl
Christoph
C
Micutkova
Lucia
L
Brunauer
Regina
R
Jamnig
Angelika
A
Trimmel
Daniela
D
Herndler-Brandstetter
Dietmar
D
Brunner
Stefan
S
Zenzmaier
Christoph
C
Sampson
Natalie
N
Breitenbach
Michael
M
Fröhlich
Kai-Uwe
KU
Grubeck-Loebenstein
Beatrix
B
Berger
Peter
P
Wieser
Matthias
M
Grillari-Voglauer
Regina
R
Thallinger
Gerhard G
GG
Grillari
Johannes
J
Trajanoski
Zlatko
Z
Madeo
Frank
F
Lepperdinger
Günter
G
Jansen-Dürr
Pidder
P
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