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

Irene Papatheodorou, Rudolfs Petrovs, Janet M. Thornton
2014 Computer applications in the biosciences : CABIOS  
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.  ...  ACKNOWLEDGEMENTS The authors thank Dobril Ivanov and Matthias Ziehm for useful discussions. Conflict of interest: none declared.  ... 
doi:10.1093/bioinformatics/btu493 pmid:25064569 pmcid:PMC4201157 fatcat:gctvdionajf4rnsh7epoeoxioq

Neuronal functions of FOXO/DAF-16

Sun Y. Kim, Ashley E. Webb
2017 Nutrition and Healthy Aging  
Similar to mammalian FOXO, the worm FOXO ortholog, called DAF-16, regulates learning and memory, regeneration, and stress resistance in neurons.  ...  Defining the function of FOXO factors in the healthy, aged, and diseased brain may have important implications for improving healthspan and treating neurodegenerative disease.  ...  Acknowledgments We thank Lauren Booth, Jana Lim, and Dervis Salih for critically reading the manuscript.  ... 
doi:10.3233/nha-160009 pmid:28447066 pmcid:PMC5389038 fatcat:nbqzb3dygrfslhgatiqrjuahse

A brief introduction to FOXOlogy

B M Th Burgering
2008 Oncogene  
downstream component of insulin signalling.  ...  Multiple signal transduction pathways regulate FOXO function, but most importantly, they are negatively regulated by protein kinase B (PKB/AKT)-mediated phosphorylation and constitute, therefore, an important  ...  Acknowledgements Work in my Laboratory is financially supported by the Dutch Cancer Foundation (KWF), Netherlands Organization of Science (NWO), Center of Biomedical Genetics (CBG) and Cancer Genomics  ... 
doi:10.1038/onc.2008.29 pmid:18391968 fatcat:k6x7sakuszempea6rybkkdga5m

Integrating Metabolism and Longevity Through Insulin and IGF1 Signaling

Marianna Sadagurski, Morris F. White
2013 Endocrinology and metabolism clinics of North America (Print)  
In this review, we explore how genetic manipulations of insulin/IGF1 signaling components are beginning to reveal neuronal circuits which might resolve the central regulation of systemic metabolism from  ...  ; however, work in flies, nematodes and mice indicate that excess insulin signaling ultimately damages cellular function and accelerates aging.  ...  Hyperactivated FoxO contributes significantly to the negative effects of hepatic insulin resistance, whereas hyperactivated FoxO might mediate some of the beneficial effects of reduce insulin signaling  ... 
doi:10.1016/j.ecl.2012.11.008 pmid:23391244 pmcid:PMC3982789 fatcat:w3v762tdyvbwtn7kgwfne6glpi

AMPK at the Nexus of Energetics and Aging

Kristopher Burkewitz, Yue Zhang, William B. Mair
2014 Cell Metabolism  
ACKNOWLEDGMENTS We apologize to those not cited due to space limitations. We thank members of the Mair lab for useful discussions and B. Manning and M. Hansen for comments on the manuscript.  ...  W.B.M. is funded by the Ellison Medical Foundation and NIH/NIA 1R01AG044346. K.B. is funded by NIH/NIA fellowship 1F32AG044944.  ...  AMPK Signaling and Aging Pathways AMPK sits upstream of multiple signal transduction pathways known to modulate the aging process. Lines represent direct signaling effects.  ... 
doi:10.1016/j.cmet.2014.03.002 pmid:24726383 pmcid:PMC4287273 fatcat:mc4drgjugvff3epgtzejc467ti

You Are What You Host: Microbiome Modulation of the Aging Process

Caroline Heintz, William Mair
2014 Cell  
ACKNOWLEDGMENTS We apologize to colleagues whose work was not cited due to space limitations. W.M. is funded by the Ellison Medical Foundation and the NIH/NIA 1R01AG044346.  ...  This work has uncovered conserved genes that modulate healthy aging in invertebrates and mammals and are linked to extreme longevity in humans (Kenyon, 2010) , including the insulin/IGF-1 like signaling  ...  Although it is too soon to know how invertebrate results will translate to mammalian aging, the studies highlight a need to consider the holobiome when thinking about the impact of single gene manipulations  ... 
doi:10.1016/j.cell.2014.01.025 pmid:24485451 pmcid:PMC3956044 fatcat:tp5c6fptgrcvvdapeve43dsg3e

Activin Signaling Targeted by Insulin/dFOXO Regulates Aging and Muscle Proteostasis in Drosophila

Hua Bai, Ping Kang, Ana Maria Hernandez, Marc Tatar, Eric Rulifson
2013 PLoS Genetics  
To understand how insulin/IGF mediates lifespan in Drosophila, we performed chromatin immunoprecipitation-sequencing analysis with the insulin/IGF regulated transcription factor dFOXO in long-lived insulin  ...  These data reveal how insulin signaling can regulate aging through control of Activin signaling that in turn controls autophagy, representing a potentially conserved molecular basis for longevity assurance  ...  We thank Jason Wood, Lingsheng Dong and the Brown Genomics Core Facility for the help of ChIP-Seq experiments and data analysis.  ... 
doi:10.1371/journal.pgen.1003941 pmid:24244197 pmcid:PMC3820802 fatcat:on5rf5o6hzhsnnympgnhmgsrnm

Cell non-autonomous regulation of health and longevity

Hillary A Miller, Elizabeth S Dean, Scott D Pletcher, Scott F Leiser
2020 eLife  
Here, we review the current landscape of research highlighting the importance of cell non-autonomous signaling in modulating aging from C. elegans to mammals.  ...  Many well-studied pathways that influence aging involve sensory cells, frequently neurons, that signal to peripheral tissues and promote survival during the presence of stress.  ...  Similar to invertebrates, insulin-like signaling represents the best studied pathway, but additional details are continuously emerging.  ... 
doi:10.7554/elife.62659 pmid:33300870 pmcid:PMC7728442 fatcat:22pcifaivjhm3hlpzkni2e452q

The main actors involved in extending the invertebrate life span

E Ottaviani, A Franchini, M Mandrioli
2014 Invertebrate Survival Journal  
It is interesting to note that pathways which lead to an extension of life span are highly conserved in animals so that "longevity pathways" identified in invertebrates provide templates for the identification  ...  In the present paper we summarize the mechanisms involved in this process with particular emphasis on the role of the fly fat body.  ...  In this context, the presence of conserved "longevity pathways" from invertebrate to vertebrates could provide templates for the identification of genes and drugs that regulate longevity and diseases in  ... 
doaj:adbc32b351a74c4e9c32f33f1f2d0d72 fatcat:o4kus2b4rneg3bfbq5q7yeuhfi

The insulin paradox: aging, proteotoxicity and neurodegeneration

Ehud Cohen, Andrew Dillin
2008 Nature Reviews Neuroscience  
2 (IRS2), an insulin signalling mediator 9 .  ...  Furthermore, an RNA interference (RNAi)-mediated reduction of AGE-1 (a central IIS-pathway component, Box 2 | Biological functions of the IIS pathway Besides lifespan, the insulin/insulin-like growth  ...  Competing interests statement The authors declare competing financial interests: see web version for details. DATABASES  ... 
doi:10.1038/nrn2474 pmid:18769445 pmcid:PMC2692886 fatcat:mf4vhit7l5d6hlhjmretf5kruq

Sestrins Link Tumor Suppressors with the AMPK-TOR Signaling Network [chapter]

Andrei V.
2012 Protein Phosphorylation in Human Health  
The author thanks Nichola Cruickshanks and Laurence Booth for the help in preparation of the manuscript. The author also thanks Nadushka Pryadilova for the everyday support.  ...  Acknowledgement This work is supported by the Department of Neurosurgery, Virginia Commonwealth University start up funds given to Andrei V. Budanov.  ...  The conservatism of the mechanisms of regulation of longevity and aging between vertebrates and invertebrates via the AMPK-TORC1 pathway support the critical role of Sestrins in regulation of aging at  ... 
doi:10.5772/48554 fatcat:2azs6zqnljbjhfr2wrun4cacye

Conserved insulin signaling in the regulation of oocyte growth, development, and maturation

Debabrata Das, Swathi Arur
2017 Molecular Reproduction and Development  
The molecular determinants of the insulin-signaling pathway, from the insulin receptor to its downstream signaling components, are structurally and functionally conserved across evolution, from worms to  ...  Insulin signaling acts cooperatively with gonadotropins in mammals and lower vertebrates to mediate various aspects of ovarian development, mainly owing to evolution of the endocrine system in vertebrates  ...  Acknowledgments Grant sponsor: This study was supported by National Institutes of Health grant GM98200, the Cancer Prevention Research Institute of Texas RP160033, and the American Cancer Society RSG-014  ... 
doi:10.1002/mrd.22806 pmid:28379636 pmcid:PMC5477485 fatcat:frvlfhzjoffivj3n3nghzgpeq4

mTOR is a key modulator of ageing and age-related disease

Simon C. Johnson, Peter S. Rabinovitch, Matt Kaeberlein
2013 Nature  
Many experts in the biology of ageing believe that pharmacological interventions to slow ageing are a matter of 'when' rather than 'if'.  ...  Although adverse side effects currently preclude use in otherwise healthy individuals, drugs that target the mTOR pathway could one day become widely used to slow ageing and reduce age-related pathologies  ...  Acknowledgments Studies related to this topic in the Kaeberlein laboratory have been supported by NIH grant R01AG039390 and R01AG031108 to M.K. S.C.J. is supported by NIH grant T32AG000057.  ... 
doi:10.1038/nature11861 pmid:23325216 pmcid:PMC3687363 fatcat:2l5xoy5jm5br5ckvbybhwpfnuu

Hydraas a tractable, long-lived model system for senescence

Anthony J. Bellantuono, Diane Bridge, Daniel E. Martínez
2014 Invertebrate reproduction & development  
Recent work has elucidated the roles of the insulin/IGF-1 signaling target FoxO, of Myc proteins, and of PIWI proteins in Hydra stem cells.  ...  Hydra represents a unique model system for the study of senescence, with the opportunity for the comparison of nonaging and induced senescence.  ...  Funding This work was supported by the National Institute on Aging [grant number 1R01AG037965-01] to DB and DM.  ... 
doi:10.1080/07924259.2014.938196 pmid:26136619 pmcid:PMC4464093 fatcat:w2hapyr22feo5pl3kftcefipey

Autophagy inDrosophila: From Historical Studies to Current Knowledge

Nitha C. Mulakkal, Peter Nagy, Szabolcs Takats, Radu Tusco, Gábor Juhász, Ioannis P. Nezis
2014 BioMed Research International  
The basic mechanisms of autophagy in fruit fly cells appear to be quite similar to other eukaryotes, and the role that this lysosomal self-degradation process plays inDrosophilamodels of various diseases  ...  The discovery of evolutionarily conserved Atg genes required for autophagy in yeast truly revolutionized this research field and made it possible to carry out functional studies on model organisms.  ...  BioMed Research International Conflict of Interests The authors declare that there is no conflict of interests regarding the publication of this paper. Authors' Contribution Nitha C.  ... 
doi:10.1155/2014/273473 pmid:24949430 pmcid:PMC4052151 fatcat:ca2wwkbrsndx3kr4bzw2rwup3q
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