Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans

  title={Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans},
  author={Heidi A. Tissenbaum and Leonard P Guarente},
In Caenorhabditis elegans, mutations that reduce the activity of an insulin-like receptor (daf-2) or a phosphatidylinositol-3-OH kinase (age-1) favour entry into the dauer state during larval development and extend lifespan in adults. Downregulation of this pathway activates a forkhead transcription factor (daf-16), which may regulate targets that promote dauer formation in larvae and stress resistance and longevity in adults. In yeast, the SIR2 gene determines the lifespan of mother cells, and… 

Reduced expression of the Caenorhabditis elegans p53 ortholog cep-1 results in increased longevity.

  • O. ArumT. Johnson
  • Biology
    The journals of gerontology. Series A, Biological sciences and medical sciences
  • 2007
It is shown that RNA interference or genetic knockout of the Caenorhabditis elegans p53 ortholog, cep-1, leads to increased life span, which is dependent upon functional daf-16, and one other DNA damage-responsive C. elegans mutant, hus-1(op241), exhibits a life-span increase.

A Transcription Elongation Factor That Links Signals from the Reproductive System to Lifespan Extension in Caenorhabditis elegans

It is suggested that TCER-1 extends lifespan by promoting the expression of a set of genes regulated by the conserved, life-extending transcription factor DAF-16/FOXO, to longevity signals from reproductive tissues.

Absence of effects of Sir2 over-expression on lifespan in C. elegans and Drosophila

These findings cast doubt on the robustness of the previously reported effects of sirtuins on lifespan in C. elegans and Drosophila and underscore the importance of controlling for genetic background and for the mutagenic effects of transgene insertions in studies of genetic effects on lifespan.

Nicotinamide adenine dinucleotide extends the lifespan of Caenorhabditis elegans mediated by sir-2.1 and daf-16

The results suggest that NAD affected lifespan through the activation of SIR-2.1 and DAF-16 along a signaling pathway, namely insulin-like signalling pathway (at least parts of it), different from that associated with caloric restriction.

Converging Pathways in the Regulation of Longevity and Metabolism in Caenorhabditis Elegans: A Dissertation

It is demonstrated that PPTR-1, a PP2A phosphatase regulatory subunit negatively regulates the IIS pathway by modulating AKT-1 dephosphorylation, and how PDP-1 is a novel link between the I IS and TGF-β signaling pathways.

Caenorhabditis elegans HCF-1 Functions in Longevity Maintenance as a DAF-16 Regulator

It is proposed that the Caenorhabditis elegans homolog of host cell factor 1 (HCF-1) represents a new longevity modulator and functions as a negative regulator of DAF-16, which modulates C. elegans longevity and stress response by forming a complex with D AF-16 and limiting a fraction of Daf-16 from accessing its target gene promoters.



An insulin-like signaling pathway affects both longevity and reproduction in Caenorhabditis elegans.

Insulin signaling, mediated by DAF-2 through the AGE-1 phosphatidylinositol-3-OH kinase, regulates reproduction and embryonic development, as well as dauer diapause and life span, and that Daf-16 transduces these signals.

Genes that regulate both development and longevity in Caenorhabditis elegans.

Genetic analysis of mutations that alter dauer larva formation (daf mutations) is presented along with an updated genetic pathway for dauer vs. nondauer development, which shows the largest genetic extension of life span yet observed in a metazoan.

The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans

It is shown that null mutations in Daf-16 suppress the effects of mutations in daf-2 or age-1; lack of dAF-16 bypasses the need for this insulin receptor-like signalling pathway.

daf-16: An HNF-3/forkhead family member that can function to double the life-span of Caenorhabditis elegans.

The wild-type Caenorhabditis elegans nematode ages rapidly, undergoing development, senescence, and death in less than 3 weeks. In contrast, mutants with reduced activity of the gene daf-2, a homolog

Two pleiotropic classes of daf-2 mutation affect larval arrest, adult behavior, reproduction and longevity in Caenorhabditis elegans.

The strengths of the Daf-c, Age, and Itt phenotypes largely correlated with each other but not with the strength of class 2-specific defects, which suggests that the DAF-2 receptor is bifunctional.

Determination of Life-Span in Caenorhabditis elegans by Four Clock Genes

Analysis of the phenotypes of these mutants suggests the existence of a general physiological clock in the worm, and the daf-2(e1370) clk-1(e2519) worms, which carry life-span-extending mutations from two different pathways, live nearly five times as long as wild-type worms.

The age-1 and daf-2 genes function in a common pathway to control the lifespan of Caenorhabditis elegans.

Findings suggest that age-1 and daf-2 mutations do act in the same lifespan pathway and extend lifespan by triggering similar if not identical processes.

The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms.

It is shown that life span regulation by the Sir proteins is independent of their role in nonhomologous end joining, and increasing the gene dosage extends the life span in wild-type cells.

A PDK1 homolog is necessary and sufficient to transduce AGE-1 PI3 kinase signals that regulate diapause in Caenorhabditis elegans.

It is shown here that a loss-of-function mutation in pdk-1, the C. elegans homolog of the mammalian Akt/PKB kinase PDK1, results in constitutive arrest at the dauer stage and increased life span; these phenotypes are suppressed by a loss of function mutation in daf-16.

The silencing protein SIR2 and its homologs are NAD-dependent protein deacetylases.

Discovery of an intrinsic deacetylation activity for the conserved SIR2 family provides a mechanism for modifying histones and other proteins to regulate transcription and diverse biological processes.