Transcriptional feedback in the insulin signalling pathway modulates ageing in both Caenorhabditis elegans and Drosophila melanogaster

Ivanov, Dobril; Papatheodorou, Irene; Ziehm, Matthias; Thornton, Janet M.

doi:10.1039/c3mb25485b

Cited by 4 publications

(3 citation statements)

References 69 publications

(95 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Protein families or human protein names are given first, with the C. elegans gene listed below those names. References (indicated by superscripts on pathway labels): 1 Kanehisa and Goto (); 2 Kanehisa et al (); 3 Ivanov et al (); 4 Murphy and Hu (); 5 Beauchamp and Plantanias (); 6 Honjoh et al (); 7 Sundaram (); 8 Inoue (); 9 Wang and Levy (); 10 Savage‐Dunn ().…”

mentioning

confidence: 99%

Environmentally induced changes in correlated responses to selection reveal variable pleiotropy across a complex genetic network

et al. 2015

View full text Add to dashboard Cite

Selection in novel environments can lead to a coordinated evolutionary response across a suite of characters. Environmental conditions can also potentially induce changes in the genetic architecture of complex traits, which in turn could alter the pattern of the multivariate response to selection. We describe a factorial selection experiment using the nematode Caenorhabditis remanei in which two different stress-related phenotypes (heat and oxidative stress resistance) were selected under three different environmental conditions. The pattern of covariation in the evolutionary response between phenotypes or across environments differed depending on the environment in which selection occurred, including asymmetrical responses to selection in some cases. These results indicate that variation in pleiotropy across the stress response network is highly sensitive to the external environment. Our findings highlight the complexity of the interaction between genes and environment that influences the ability of organisms to acclimate to novel environments. They also make clear the need to identify the underlying genetic basis of genetic correlations in order understand how patterns of pleiotropy are distributed across complex genetic networks.

show abstract

mentioning

confidence: 99%

Environmentally induced changes in correlated responses to selection reveal variable pleiotropy across a complex genetic network

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Given a gene mutation and the resulting genome-wide differential gene expression, NetEffects will deduce signalling effects and how they can influence lifespan according to the prior knowledge. Our applications on fly and worm datasets ( Ivanov et al , 2013 ; Papatheodorou et al , 2012 ) have revealed consistent homeostatic mechanisms across both long- and short-lived mutants.…”

Section: Introductionmentioning

confidence: 82%

“…In mice, we observe more copies of certain proteins, such as four copies of AKT ( Akt1-4 ) instead of one in the fly and two in the worm and four genes encoding FOXO ( Foxo1 , Foxo2 , Foxo4 and Foxo6 ) in contrast to a single FOXO in flies and worms ( foxo and daf-16 ). The TOR pathway is remarkably similar between flies and mice, but exhibits differences with the worm ( Ivanov et al , 2013 ; Riesen et al , 2014 ).…”

Section: Introductionmentioning

confidence: 99%

Comparison of the mammalian insulin signalling pathway to invertebrates in the context of FOXO-mediated ageing

2014

Self Cite

View full text Add to dashboard Cite

Motivation: A large number of experimental studies on ageing focus on the effects of genetic perturbations of the insulin/insulin-like growth factor signalling pathway (IIS) on lifespan. Short-lived invertebrate laboratory model organisms are extensively used to quickly identify ageing-related genes and pathways. It is important to extrapolate this knowledge to longer lived mammalian organisms, such as mouse and eventually human, where such analyses are difficult or impossible to perform. Computational tools are needed to integrate and manipulate pathway knowledge in different species.Results: We performed a literature review and curation of the IIS and target of rapamycin signalling pathways in Mus Musculus. We compare this pathway model to the equivalent models in Drosophila melanogaster and Caenorhabtitis elegans. Although generally well-conserved, they exhibit important differences. In general, the worm and mouse pathways include a larger number of feedback loops and interactions than the fly. We identify ‘functional orthologues’ that share similar molecular interactions, but have moderate sequence similarity. Finally, we incorporate the mouse model into the web-service NetEffects and perform in silico gene perturbations of IIS components and analyses of experimental results. We identify sub-paths that, given a mutation in an IIS component, could potentially antagonize the primary effects on ageing via FOXO in mouse and via SKN-1 in worm. Finally, we explore the effects of FOXO knockouts in three different mouse tissues.Availability and implementation: http://www.ebi.ac.uk/thornton-srv/software/NetEffectsContact: ip8@sanger.ac.uk or thornton@ebi.ac.ukSupplementary information: Supplementary data are available at Bioinformatics online.

show abstract

Some naturally occurring compounds that increase longevity and stress resistance in model organisms of aging

et al. 2019

View full text Add to dashboard Cite

Transcriptional feedback in the insulin signalling pathway modulates ageing in both Caenorhabditis elegans and Drosophila melanogaster

Abstract: Using manually curated signalling models of the IIS/TOR pathways, transcriptional feedback is shown to modulate ageing in worms and flies.

Cited by 4 publications

References 69 publications

Environmentally induced changes in correlated responses to selection reveal variable pleiotropy across a complex genetic network

Environmentally induced changes in correlated responses to selection reveal variable pleiotropy across a complex genetic network

Comparison of the mammalian insulin signalling pathway to invertebrates in the context of FOXO-mediated ageing

Some naturally occurring compounds that increase longevity and stress resistance in model organisms of aging

Contact Info

Product

Resources

About