Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans

Murphy, Coleen T.; McCarroll, Steven A.; Bargmann, Cornelia I.; Fraser, Andrew G.; Kamath, Ravi S.; Ahringer, Julie; Li, Hao; Kenyon, Cynthia

doi:10.1038/nature01789

Cited by 2,017 publications

(2,301 citation statements)

References 51 publications

Supporting

110

Mentioning

2,160

Contrasting

Unclassified

Order By: Relevance

“…For example, the IIS pathway regulates the metabolism, development, and lifespan of C. elegans . Insulin‐like receptor (IR) is a transmembrane receptor that negatively regulates FOXO, which in turn promotes the expression of genes that confer extended longevity and enhance stress resistance (Lee et al ., 2003; Murphy et al ., 2003). To evaluate the involvement of IR and FOXO in the signaling pathway regulated by feeding with LG2055, we monitored the survival rates of daf‐2 (e1368) and daf‐16 (mgDf50) C. elegans mutants, respectively.…”

Section: Resultsmentioning

confidence: 99%

“…This is because it has an evolutionarily conserved metabolism and host defense mechanisms, including insulin/insulin‐like growth factor (IGF‐1) pathway, that is, the IIS pathway (Murphy et al ., 2003), p38 mitogen‐activated protein kinase (p38 MAPK) pathway (Kim et al ., 2002), and transforming growth factor‐β (TGF‐β) signaling pathway (Zugasti & Ewbank, 2009). Moreover, dietary resources, such as bacteria, play an important role in the control of the lifespan of C. elegans (So et al ., 2011).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effects and mechanisms of prolongevity induced by Lactobacillus gasseri SBT2055 in Caenorhabditis elegans

et al. 2015

View full text Add to dashboard Cite

SummaryLactic‐acid bacteria are widely recognized beneficial host associated groups of the microbiota of humans and animals. Some lactic‐acid bacteria have the ability to extend the lifespan of the model animals. The mechanisms behind the probiotic effects of bacteria are not entirely understood. Recently, we reported the benefit effects of Lactobacillus gasseri SBT2055 (LG2055) on animal and human health, such as preventing influenza A virus, and augmentation of IgA production. Therefore, it was preconceived that LG2055 has the beneficial effects on longevity and/or aging. We examined the effects of LG2055 on lifespan and aging of Caenorhabditis elegans and analyzed the mechanism of prolongevity. Our results demonstrated that LG2055 has the beneficial effects on longevity and anti‐aging of C. elegans. Feeding with LG2055 upregulated the expression of the skn‐1 gene and the target genes of SKN‐1, encoding the antioxidant proteins enhancing antioxidant defense responses. We found that feeding with LG2055 directly activated SKN‐1 activity via p38 MAPK pathway signaling. The oxidative stress response is elicited by mitochondrial dysfunction in aging, and we examined the influence of LG2055 feeding on the membrane potential of mitochondria. Here, the amounts of mitochondria were significantly increased by LG2055 feeding in comparison with the control. Our result suggests that feeding with LG2055 is effective to the extend lifespan in C. elegans by a strengthening of the resistance to oxidative stress and by stimulating the innate immune response signaling including p38MAPK signaling pathway and others.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects and mechanisms of prolongevity induced by Lactobacillus gasseri SBT2055 in Caenorhabditis elegans

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Briefly, insulin or IGF‐1 triggers an intracellular pathway mediated by PI3K‐AKT, allowing phosphorylation of FOXO factors by the serine/threonine kinase AKT at three conserved residues within the FOXO proteins. AKT‐mediated phosphorylation of FOXO leads to its nuclear exclusion and, in turn, to suppression of FOXO‐dependent transcription of target genes (Guo et al ., 1999; Murphy et al ., 2003). Conversely, in the absence of growth factor signaling or upon cellular stress, FOXOs translocate into the nucleus and activate FOXO‐dependent gene expression.…”

Section: Foxo Transcription Factorsmentioning

confidence: 99%

“…DAF‐16/FoxO has been shown to regulate hundreds of genes in C. elegans including those related to stress response, antimicrobial activity, and metabolism, unveiling DAF‐16/FoxO as a central player of a complex network involving multiple upstream pathways and downstream target genes (Lee et al ., 2003; McElwee et al ., 2003; Murphy et al ., 2003). The lifespan expansion effect accomplished by DAF‐16/FOXO is most likely due to two isoform variants DAF‐16a and DAF‐16d/f (Kwon et al ., 2010; Chen et al ., 2015).…”

Section: Animal Modelsmentioning

confidence: 99%

Long live FOXO: unraveling the role of FOXO proteins in aging and longevity

2015

View full text Add to dashboard Cite

SummaryAging constitutes the key risk factor for age‐related diseases such as cancer and cardiovascular and neurodegenerative disorders. Human longevity and healthy aging are complex phenotypes influenced by both environmental and genetic factors. The fact that genetic contribution to lifespan strongly increases with greater age provides basis for research on which “protective genes” are carried by long‐lived individuals. Studies have consistently revealed FOXO (Forkhead box O) transcription factors as important determinants in aging and longevity. FOXO proteins represent a subfamily of transcription factors conserved from Caenorhabditis elegans to mammals that act as key regulators of longevity downstream of insulin and insulin‐like growth factor signaling. Invertebrate genomes have one FOXO gene, while mammals have four FOXO genes: FOXO1, FOXO3, FOXO4, and FOXO6. In mammals, this subfamily is involved in a wide range of crucial cellular processes regulating stress resistance, metabolism, cell cycle arrest, and apoptosis. Their role in longevity determination is complex and remains to be fully elucidated. Throughout this review, the mechanisms by which FOXO factors contribute to longevity will be discussed in diverse animal models, from Hydra to mammals. Moreover, compelling evidence of FOXOs as contributors for extreme longevity and health span in humans will be addressed.

show abstract

“…Whereas McElwee et al (2004) used cDNA microarrays for a similar comparison, we used Serial Analysis of Gene Expression, or SAGE (Velculescu et al, 1995) to identify potential novel regulators of life span, and to characterize the expression profiles of different gene families that were previously shown to be associated with aging (Lund et al, 2002;Murphy et al, 2003). SAGE data for daf-2 and wild-type adults were compared in a previous study (Halaschek-Wiener et al, 2005), which showed general inhibition of metabolism in the middleaged daf-2 adults.…”

Section: Introductionmentioning

confidence: 99%

Genes that may modulate longevity in C. elegans in both dauer larvae and long-lived daf-2 adults

Ruzanov

Riddle

Marra

et al. 2007

Experimental Gerontology

View full text Add to dashboard Cite

SummaryWe used Serial Analysis of Gene Expression (SAGE) to compare the global transcription profiles of long-lived mutant daf-2 adults and dauer larvae, aiming to identify aging-related genes based on similarity of expression patterns. Genes that are expressed similarly in both long-lived types potentially define a common life-extending program. Comparison of eight SAGE libraries yielded a set of 120 genes, the expression of which was significantly different in long-lived worms versus normal adults. The gene annotations indicate a strong link between oxidative stress and life span, further supporting the hypothesis that metabolic activity is a major determinant in longevity. The SAGE data show changes in mRNA levels for electron transport chain components, elevated expression of glyoxylate shunt enzymes and significantly reduced expression for components of the TCA cycle in longer-lived nematodes. We propose a model for enhanced longevity through a cytochrome c oxidase-mediated reduction in reactive oxygen species commonly held to be a major contributor to aging.

show abstract

Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans

Cited by 2,017 publications

References 51 publications

Effects and mechanisms of prolongevity induced by Lactobacillus gasseri SBT2055 in Caenorhabditis elegans

Effects and mechanisms of prolongevity induced by Lactobacillus gasseri SBT2055 in Caenorhabditis elegans

Long live FOXO: unraveling the role of FOXO proteins in aging and longevity

Genes that may modulate longevity in C. elegans in both dauer larvae and long-lived daf-2 adults

Contact Info

Product

Resources

About