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A role for SIR-2.1 regulation of ER stress response genes in determining C. elegans life span

ABSTRACT: Abstract: C. elegans SIR-2.1, a member of the Sir-2 family of NAD(+)-dependent protein deacetylases, has been shown to regulate nematode aging via the insulin/IGF pathway transcription factor daf-16. Treatment of C. elegans with the small molecule resveratrol, however, extends life span in a manner fully dependent upon sir-2.1, but independent of daf-16. Microarray analysis of worms treated with resveratrol demonstrates the transcriptional induction of a family of genes encoding prion-like glutamine/asparagine-rich proteins involved in endoplasmic reticulum (ER) stress response to unfolded proteins. RNA interference of abu-11, a member of this ER stress gene family, abolishes resveratrol-mediated life span extension, and overexpression of abu-11 extends the life span of transgenic animals. Furthermore, SIR-2.1 normally represses transcription of abu-11 and other ER stress gene family members, indicating that resveratrol extends life span by inhibiting sir-2.1-mediated repression of ER stress genes. Our findings demonstrate that abu-11 and other members of its ER stress gene family are positive determinants of C. elegans life span. This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Caenorhabditis elegans

PROVIDER: GSE4402 | GEO | 2006/03/08

SECONDARY ACCESSION(S): PRJNA94629

REPOSITORIES: GEO

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A role for SIR-2.1 regulation of ER stress response genes in determining C. elegans life span

Project description:This SuperSeries is composed of the following subset Series: GSE4093: Resveratrol treatment of daf-16 mutant C. elegans GSE4094: N2 worms treated with Resveratrol GSE4095: Sir-2.1 low copy transgenic Abstract: C. elegans SIR-2.1, a member of the Sir-2 family of NAD(+)-dependent protein deacetylases, has been shown to regulate nematode aging via the insulin/IGF pathway transcription factor daf-16. Treatment of C. elegans with the small molecule resveratrol, however, extends life span in a manner fully dependent upon sir-2.1, but independent of daf-16. Microarray analysis of worms treated with resveratrol demonstrates the transcriptional induction of a family of genes encoding prion-like glutamine/asparagine-rich proteins involved in endoplasmic reticulum (ER) stress response to unfolded proteins. RNA interference of abu-11, a member of this ER stress gene family, abolishes resveratrol-mediated life span extension, and overexpression of abu-11 extends the life span of transgenic animals. Furthermore, SIR-2.1 normally represses transcription of abu-11 and other ER stress gene family members, indicating that resveratrol extends life span by inhibiting sir-2.1-mediated repression of ER stress genes. Our findings demonstrate that abu-11 and other members of its ER stress gene family are positive determinants of C. elegans life span. Refer to individual Series

2006-03-07 | E-GEOD-4402 | biostudies-arrayexpress

Project description:A role for SIR-2.1 regulation of ER stress response genes in determining C. elegans life span

| PRJNA94629 | ENA

Deep sequencing of endogenous mRNA from Caenorhabditis elegans in the presence and absence of 1-methylnicotinamide (MNA) and nicotinic acid (NA)

Project description:Sirtuins, a family of histone deacetylases, have a fiercely debated role in regulating lifespan of different species. Contrasting recent observations, we here find that overexpression of sir-2.1, the orthologue of mammalian SirT1, does extend C. elegans lifespan. Sirtuins are known to convert NAD+ into nicotinamide (NAM). We here find that NAM and its metabolite, 1-methylnicotinamide (MNA), extend C. elegans lifespan, also in the absence of sir-2.1. Consistently, impairment of sir-2.1 prevents extension of lifespan by nicotinic acid (NA), a NAD+ precursor. Taken together, sirtuins extend lifespan by promoting formation of MNA to generate a phase I - mediated ROS signal, providing an unexpected mechanistic role for sirtuins beyond histone deacetylation.

2013-08-09 | GSE49662 | GEO

Deep sequencing of endogenous mRNA from Caenorhabditis elegans in the presence and absence of 1-methylnicotinamide (MNA) and nicotinic acid (NA)

2013-08-09 | E-GEOD-49662 | biostudies-arrayexpress

Caenorhabditis elegans

Project description:Sir-2.1 low copy transgenic

| PRJNA104893 | ENA

Nuclear tRNA sequestering slows aging by a mechanism similar to dietary restriction

Project description:Dietary restriction (DR) is the best-characterized intervention for slowing aging, and reduced signaling through the target of rapamycin (TOR) kinase is believed to be one of the key mechanisms by which DR extends life span in organisms from yeast to mammals. Here we describe a role for nuclear sequestration of tRNA in yeast replicative life span (RLS) extension from DR. DR causes the nuclear tRNA exporter Los1 to become depleted from the nucleus by a mechanism that requires the DNA damage response factor Rad53, and deletion of LOS1 or overexpression of RAD53 is sufficient to extend RLS. We further report that activation of the nitrogen responsive transcription factor Gln3 is the primary mechanism by which DR extends RLS. Gln3 is activated by both branches of the DR response and is required for life span extension. Overexpression of Gln3 extends RLS by approximately 50%.

2015-02-03 | GSE37241 | GEO

Nuclear tRNA sequestering slows aging by a mechanism similar to dietary restriction

2015-02-03 | E-GEOD-37241 | biostudies-arrayexpress

Rapamycin extends life span, but has limited effects on aging in mice

Project description:Rapamycin extends life span in mice, but it remains unclear if this compound also delays mammalian aging. Here, we present results from a comprehensive large-scale assessment of a wide rage of structural and functional aging phenotypes in mice. Rapamycin extended life span but showed few effects on a large number of systemic aging phenotypes, suggesting that rapamycin's effects on aging are largely limited to the regulation of age-related mortality and carcinogenesis.

2013-07-29 | GSE41018 | GEO

Rapamycin extends life span, but has limited effects on aging in mice

2013-07-29 | E-GEOD-41018 | biostudies-arrayexpress

Mus musculus

Project description:Rapamycin extends life span, but has limited effects on aging in mice

| PRJNA175551 | ENA