Aging (Caenorhabditis elegans)

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1, 7614, 154612151554, 151212151410, 13PLongevity reducing actionPhosphorylatedConverts toTranslocatesInsulin-like signalsOxidative stress responseInnate immunityDNA damageProteosome degradationpathwayBinds toBlocks action, inhibitsActivates through modificationKEYReproductive LongevityDauer DevelopmentLongevity promoting actionActivates in generalPIP2DAF-18/PTENAGE-1/PI3K14-3-33DAF-2/InR5, 118PIP3PDK-1/PKD1AKT-1/Akt/PKB124, 12AKT-2/Akt/PKB4, 12DAF-16/FOXO2, 4, 9, 15JNK-1PDAF-16/FOXO14P2, 9, 14JKK-11414PRMT-115DAF-16/FOXODAF-16/FOXOMe15P6RLE-1SMK-16SGK-113daf-1513MeMethylated


Aging encompasses the decline of physical, metabolic, and behavioral aspects of an animal as it progresses over time beyond the developmental growth period. Extensive work on adult C. elegans animals has elucidated genes involved in the many processes involved in or affected by aging.

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  1. Kimura KD, Tissenbaum HA, Liu Y, Ruvkun G; ''daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans.''; Science, 1997 PubMed Europe PMC
  2. Lapierre LR, Hansen M; ''Lessons from C. elegans: signaling pathways for longevity.''; Trends Endocrinol Metab, 2012 PubMed Europe PMC
  3. Paradis S, Ruvkun G; ''Caenorhabditis elegans Akt/PKB transduces insulin receptor-like signals from AGE-1 PI3 kinase to the DAF-16 transcription factor.''; Genes Dev, 1998 PubMed Europe PMC
  4. Ogg S, Paradis S, Gottlieb S, Patterson GI, Lee L, Tissenbaum HA, Ruvkun G; ''The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans.''; Nature, 1997 PubMed Europe PMC
  5. Paradis S, Ailion M, Toker A, Thomas JH, Ruvkun G; ''A PDK1 homolog is necessary and sufficient to transduce AGE-1 PI3 kinase signals that regulate diapause in Caenorhabditis elegans.''; Genes Dev, 1999 PubMed Europe PMC
  6. Zhou KI, Pincus Z, Slack FJ; ''Longevity and stress in Caenorhabditis elegans.''; Aging (Albany NY), 2011 PubMed Europe PMC
  7. Ogg S, Ruvkun G; ''The C. elegans PTEN homolog, DAF-18, acts in the insulin receptor-like metabolic signaling pathway.''; Mol Cell, 1998 PubMed Europe PMC
  8. Oh SW, Mukhopadhyay A, Svrzikapa N, Jiang F, Davis RJ, Tissenbaum HA; ''JNK regulates lifespan in Caenorhabditis elegans by modulating nuclear translocation of forkhead transcription factor/DAF-16.''; Proc Natl Acad Sci U S A, 2005 PubMed Europe PMC
  9. Morris JZ, Tissenbaum HA, Ruvkun G; ''A phosphatidylinositol-3-OH kinase family member regulating longevity and diapause in Caenorhabditis elegans.''; Nature, 1996 PubMed Europe PMC
  10. Wolff S, Ma H, Burch D, Maciel GA, Hunter T, Dillin A; ''SMK-1, an essential regulator of DAF-16-mediated longevity.''; Cell, 2006 PubMed Europe PMC
  11. Larsen PL, Albert PS, Riddle DL; ''Genes that regulate both development and longevity in Caenorhabditis elegans.''; Genetics, 1995 PubMed Europe PMC
  12. Takahashi Y, Daitoku H, Hirota K, Tamiya H, Yokoyama A, Kako K, Nagashima Y, Nakamura A, Shimada T, Watanabe S, Yamagata K, Yasuda K, Ishii N, Fukamizu A; ''Asymmetric arginine dimethylation determines life span in C. elegans by regulating forkhead transcription factor DAF-16.''; Cell Metab, 2011 PubMed Europe PMC
  13. Lin K, Dorman JB, Rodan A, Kenyon C; ''daf-16: An HNF-3/forkhead family member that can function to double the life-span of Caenorhabditis elegans.''; Science, 1997 PubMed Europe PMC
  14. Dillin A, Crawford DK, Kenyon C; ''Timing requirements for insulin/IGF-1 signaling in C. elegans.''; Science, 2002 PubMed Europe PMC
  15. Li W, Gao B, Lee SM, Bennett K, Fang D; ''RLE-1, an E3 ubiquitin ligase, regulates C. elegans aging by catalyzing DAF-16 polyubiquitination.''; Dev Cell, 2007 PubMed Europe PMC


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107082view14:16, 17 September 2019MaintBotChEBI identifier normalization
95994view09:07, 13 February 2018MaintBotCosmetic changes, e.g., interactions black and 1px
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External references


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NameTypeDatabase referenceComment
AGE-1/PI3KGeneProductB0334.8 (WormBase) age-1 encodes a homologue of mammalian phosphatidylinositol-3-OH kinase catalytic subunit.
AKT-1/Akt/PKBGeneProductC12D8.10 (WormBase)
AKT-2/Akt/PKBGeneProductF28H6.1 (WormBase)
DAF-16/FOXOGeneProductR13H8.1 (WormBase)
DAF-18/PTENGeneProductT07A9.6 (WormBase)
  • daf-18 functions upstream to akt-1 and akt-2
  • daf-18 acts downstream of age-1
DAF-2/InRGeneProductY55D5A.5 (WormBase) insulin/IGF-1 pathway can diverge to regulate the timing of reproduction independently of longevity (Dillin et al., 2002a).
JKK-1GeneProductF35C8.3 (WormBase)
JNK-1GeneProductB0478.1 (WormBase)
  • DAF-16 binds to JNK-1.
  • JNK-1 binds and phosphorylates DAF-16.
PDK-1/PKD1GeneProductH42K12.1 (WormBase)
PIP2Metabolite18348 (ChEBI)
PIP3Metabolite16618 (ChEBI)
PRMT-1GeneProductY113G7B.17 (WormBase)
RLE-1GeneProductM142.6 (WormBase)
  • age-1 encodes a homologue of mammalian phosphatidylinositol-3-OH kinase catalytic subunit.
  • RLE-1 physically interacts with DAF-16. RLE-1 C terminus is required for the interaction of RLE-1 with DAF-16.
SGK-1GeneProductW10G6.2 (WormBase) DAF-16 is predominantly localized in the cytoplasm as a result of inhibitory phosphorylation of Ser/Thr residues by the AKT and SGK kinases.
SMK-1GeneProductF41E6.4 (WormBase)
  • SMK-1 was temporally and spatially colocalized with active DAF-16.
  • smk-1 RNAi does not cause a general sickness in long-lived animals but rather specifically affects IIS-regulated life span.
  • DAF-16 and SMK-1 do not directly or indirectly regulate expression or localization of one another.
  • SMK-1 specifies the longevity function of DAF-16 by affecting the efficiency of transcription of DAF-16 target genes involved in oxidative and UV stress response and innate immunity but is not required for DAF-16 regulation of heat-stress-response genes.
daf-15GeneProductC10C5.6 (WormBase) Reduced smk-1 resulted in increased expression of daf-15 mRNA, suggesting that SMK-1 is required for the transcriptional repressor activity of DAF-16

Annotated Interactions

No annotated interactions

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