A novel gene-diet pair modulates C. elegans aging

Verma, Sonia; Jagtap, Urmila; Goyala, Anita; Mukhopadhyay, Arnab

doi:10.1371/journal.pgen.1007608

Cited by 27 publications

(54 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The gene encoding for the Toll/interleukin-1 receptor adaptor protein TIR-1, an essential component of the innate immune response in nematodes (Liberati et al 2004), was found to be significantly upregulated in both hsb-1(-) and hsf-1 overexpression strains (Tables S1 and S2). Interestingly, a recent study has shown a major role of tir-1 in mediating the life span extension associated with activation of p38 MAPK pathway in C. elegans (Verma et al 2018).…”

Section: Resultsmentioning

confidence: 99%

HSB-1 Inhibition and HSF-1 Overexpression Trigger Overlapping Transcriptional Changes To Promote Longevity in Caenorhabditis elegans

Sural¹,

Jung³

et al. 2019

G3 Genes|Genomes|Genetics

View full text Add to dashboard Cite

Heat shock factor 1 ( HSF-1 ) is a component of the heat shock response pathway that is induced by cytoplasmic proteotoxic stress. In addition to its role in stress response, HSF-1 also acts as a key regulator of the rate of organismal aging. Overexpression of HSF-1 promotes longevity in C. elegans via mechanisms that remain less understood. Moreover, genetic ablation of a negative regulator of HSF-1 , termed as heat shock factor binding protein 1 ( HSB-1 ), results in hsf-1 -dependent life span extension in animals. Here we show that in the absence of HSB-1 , HSF-1 acquires increased DNA binding activity to its genomic target sequence. Using RNA-Seq to compare the gene expression profiles of the hsb-1 mutant and hsf-1 overexpression strains, we found that while more than 1,500 transcripts show ≥1.5-fold upregulation due to HSF-1 overexpression, HSB-1 inhibition alters the expression of less than 500 genes in C. elegans . Roughly half of the differentially regulated transcripts in the hsb-1 mutant have altered expression also in hsf-1 overexpressing animals, with a strongly correlated fold-expression pattern between the two strains. In addition, genes that are upregulated via both HSB-1 inhibition and HSF-1 overexpression include numerous DAF-16 targets that have known functions in longevity regulation. This study identifies how HSB-1 acts as a specific regulator of the transactivation potential of HSF-1 in non-stressed conditions, thus providing a detailed understanding of the role of HSB-1 / HSF-1 signaling pathway in transcriptional regulation and longevity in C. elegans .

show abstract

Section: Resultsmentioning

confidence: 99%

HSB-1 Inhibition and HSF-1 Overexpression Trigger Overlapping Transcriptional Changes To Promote Longevity in Caenorhabditis elegans

Sural¹,

Jung³

et al. 2019

G3 Genes|Genomes|Genetics

View full text Add to dashboard Cite

show abstract

“…The p38-MAPK pathway mutants were susceptible to oxidative stress 14 . The increased life span of daf-2 mutants 15 and the food-type dependent life span of flr-4 mutant are dependent on p38-MAPK pathway components 70 . In most of the cases, the activation of the p38-MAPK pathway correlates with the phenotype.…”

Section: Discussionmentioning

confidence: 97%

“…The C. elegans p38-MAPK pathway is involved in diverse aspects of cellular function, including development 65,66 , stress response 14,18 , innate immunity 15,25,67,68 , metabolism, and longevity 69,70 . In all these cases, when a component of the p38-MAPK pathway was mutated, the phenotype was adversely affected.…”

Section: Discussionmentioning

confidence: 99%

“…In most of the cases, the activation of the p38-MAPK pathway correlates with the phenotype. For instance, the phosphorylation of PMK-1 is increased on oxidative stress 14 and flr-4 mutant worms have higher phospho-PMK-1 on E. coli HT115 bacteria 70 . Although the phosphorylation of PMK-1 has not been directly elucidated on challenge with pathogenic bacteria, susceptible worms have lower amount of pPMK-1 67,68 .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Polyunsaturated fatty acids and p38-MAPK link metabolic reprogramming to cytoprotective gene expression during dietary restriction

et al. 2020

Self Cite

View full text Add to dashboard Cite

The metabolic state of an organism instructs gene expression modalities, leading to changes in complex life history traits, such as longevity. Dietary restriction (DR), which positively affects health and life span across species, leads to metabolic reprogramming that enhances utilisation of fatty acids for energy generation. One direct consequence of this metabolic shift is the upregulation of cytoprotective (CyTP) genes categorized in the Gene Ontology (GO) term of “Xenobiotic Detoxification Program” (XDP). How an organism senses metabolic changes during nutritional stress to alter gene expression programs is less known. Here, using a genetic model of DR, we show that the levels of polyunsaturated fatty acids (PUFAs), especially linoleic acid (LA) and eicosapentaenoic acid (EPA), are increased following DR and these PUFAs are able to activate the CyTP genes. This activation of CyTP genes is mediated by the conserved p38 mitogen-activated protein kinase (p38-MAPK) pathway. Consequently, genes of the PUFA biosynthesis and p38-MAPK pathway are required for multiple paradigms of DR-mediated longevity, suggesting conservation of mechanism. Thus, our study shows that PUFAs and p38-MAPK pathway function downstream of DR to help communicate the metabolic state of an organism to regulate expression of CyTP genes, ensuring extended life span.

show abstract

“…Furthermore, the effects on lifespan, when manipulating orthologous lifespan-associated genes in different model organisms, are mostly concordant, despite high evolutionary distances between them [ 15 ]. Most recently, C. elegans has come to enjoy increasing popularity as a model for health [ 16 , 17 ], and an ever increasing number of compounds [ 18 – 21 ] and diets [ 22 , 23 ] are tested in C. elegans for their anti-ageing and health effects.…”

Section: Introductionmentioning

confidence: 99%

Healthspan pathway maps in C. elegans and humans highlight transcription, proliferation/biosynthesis and lipids

Möller

Saul

Cohen

et al. 2020

Aging

View full text Add to dashboard Cite

The molecular basis of aging and of aging-associated diseases is being unraveled at an increasing pace. An extended healthspan, and not merely an extension of lifespan, has become the aim of medical practice. Here, we define health based on the absence of diseases and dysfunctions. Based on an extensive review of the literature, in particular for humans and C. elegans , we compile a list of features of health and of the genes associated with them. These genes may or may not be associated with survival/lifespan. In turn, survival/lifespan genes that are not known to be directly associated with health are not considered. Clusters of these genes based on molecular interaction data give rise to maps of healthspan pathways for humans and for C. elegans . Overlaying healthspan-related gene expression data onto the healthspan pathway maps, we observe the downregulation of (pro-inflammatory) Notch signaling in humans and of proliferation in C. elegans . We identify transcription, proliferation/biosynthesis and lipids as a common theme on the annotation level, and proliferation-related kinases on the gene/protein level. Our literature-based data corpus, including visualization, should be seen as a pilot investigation of the molecular underpinnings of health in two different species. Web address: http://pathways.h2020awe.eu .

show abstract

A novel gene-diet pair modulates C. elegans aging

Cited by 27 publications

References 59 publications

HSB-1 Inhibition and HSF-1 Overexpression Trigger Overlapping Transcriptional Changes To Promote Longevity in Caenorhabditis elegans

HSB-1 Inhibition and HSF-1 Overexpression Trigger Overlapping Transcriptional Changes To Promote Longevity in Caenorhabditis elegans

Polyunsaturated fatty acids and p38-MAPK link metabolic reprogramming to cytoprotective gene expression during dietary restriction

Healthspan pathway maps in C. elegans and humans highlight transcription, proliferation/biosynthesis and lipids

Contact Info

Product

Resources

About