Open AccessIdentification of evolutionarily conserved genetic regulators of cellular aging
Author(s) -
Laschober Gerhard T.,
Ruli Doris,
Hofer Edith,
Muck Christoph,
CarmonaGutierrez Didac,
Ring Julia,
Hutter Eveline,
Ruckenstuhl Christoph,
Micutkova Lucia,
Brunauer Regina,
Jamnig Angelika,
Trimmel Daniela,
HerndlerBrandstetter Dietmar,
Brunner Stefan,
Zenzmaier Christoph,
Sampson Natalie,
Breitenbach Michael,
Fröhlich KaiUwe,
GrubeckLoebenstein Beatrix,
Berger Peter,
Wieser Matthias,
GrillariVoglauer Regina,
Thallinger Gerhard G.,
Grillari Johannes,
Trajanoski Zlatko,
Madeo Frank,
Lepperdinger Günter,
JansenDürr Pidder
Publication year - 2010
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/j.1474-9726.2010.00637.x
Subject(s) - biology , gene , genetics , senescence , phenotype , cellular model , model organism , genome , saccharomyces cerevisiae , conserved sequence , gene expression profiling , computational biology , candidate gene , gene expression , peptide sequence , cell culture
Summary 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.