Chemical activation of a food deprivation signal extends lifespan

Summary Model organisms subject to dietary restriction (DR) generally live longer. Accompanying this lifespan extension are improvements in overall health, based on multiple metrics. This indicates that pharmacological treatments that mimic the effects of DR could improve health in humans. To find n...

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Published inAging cell Vol. 15; no. 5; pp. 832 - 841
Main Authors Lucanic, Mark, Garrett, Theo, Yu, Ivan, Calahorro, Fernando, Asadi Shahmirzadi, Azar, Miller, Aaron, Gill, Matthew S., Hughes, Robert E., Holden‐Dye, Lindy, Lithgow, Gordon J.
Format Journal Article
LanguageEnglish
Published England John Wiley & Sons, Inc 01.10.2016
John Wiley and Sons Inc
Subjects
Aging
Animals
Caenorhabditis
Caenorhabditis elegans - physiology
Caenorhabditis elegans Proteins - metabolism
Caloric Restriction
Chloride Channels - metabolism
dietary restriction
Drug Discovery
Feeding Behavior - drug effects
Food Deprivation - physiology
Glutamate
Glutamates - metabolism
Health aspects
Longevity - drug effects
Longevity - physiology
Models, Biological
Muscle Contraction - drug effects
Mutation - genetics
Neurophysiology
Original
Pharmacogenetics
Pharynx - drug effects
Pharynx - physiology
Receptors, Muscarinic - genetics
Receptors, Muscarinic - metabolism
Signal Transduction - drug effects
Small Molecule Libraries - analysis
Small Molecule Libraries - chemistry
Small Molecule Libraries - pharmacology
Aging
Caenorhabditis
Pharmacogenetics
Drug Discovery
dietary restriction
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Abstract Summary Model organisms subject to dietary restriction (DR) generally live longer. Accompanying this lifespan extension are improvements in overall health, based on multiple metrics. This indicates that pharmacological treatments that mimic the effects of DR could improve health in humans. To find new chemical structures that extend lifespan, we screened 30 000 synthetic, diverse drug‐like chemicals in Caenorhabditis elegans and identified several structurally related compounds that acted through DR mechanisms. The most potent of these NP1 impinges upon a food perception pathway by promoting glutamate signaling in the pharynx. This results in the overriding of a GPCR pathway involved in the perception of food and which normally acts to decrease glutamate signals. Our results describe the activation of a dietary restriction response through the pharmacological masking of a novel sensory pathway that signals the presence of food. This suggests that primary sensory pathways may represent novel targets for human pharmacology.
AbstractList Model organisms subject to dietary restriction (DR) generally live longer. Accompanying this lifespan extension are improvements in overall health, based on multiple metrics. This indicates that pharmacological treatments that mimic the effects of DR could improve health in humans. To find new chemical structures that extend lifespan, we screened 30 000 synthetic, diverse drug-like chemicals in Caenorhabditis elegans and identified several structurally related compounds that acted through DR mechanisms. The most potent of these NP1 impinges upon a food perception pathway by promoting glutamate signaling in the pharynx. This results in the overriding of a GPCR pathway involved in the perception of food and which normally acts to decrease glutamate signals. Our results describe the activation of a dietary restriction response through the pharmacological masking of a novel sensory pathway that signals the presence of food. This suggests that primary sensory pathways may represent novel targets for human pharmacology.
Model organisms subject to dietary restriction (DR) generally live longer. Accompanying this lifespan extension are improvements in overall health, based on multiple metrics. This indicates that pharmacological treatments that mimic the effects of DR could improve health in humans. To find new chemical structures that extend lifespan, we screened 30 000 synthetic, diverse drug-like chemicals in Caenorhabditis elegans and identified several structurally related compounds that acted through DR mechanisms. The most potent of these NP1 impinges upon a food perception pathway by promoting glutamate signaling in the pharynx. This results in the overriding of a GPCR pathway involved in the perception of food and which normally acts to decrease glutamate signals. Our results describe the activation of a dietary restriction response through the pharmacological masking of a novel sensory pathway that signals the presence of food. This suggests that primary sensory pathways may represent novel targets for human pharmacology.
Summary Model organisms subject to dietary restriction (DR) generally live longer. Accompanying this lifespan extension are improvements in overall health, based on multiple metrics. This indicates that pharmacological treatments that mimic the effects of DR could improve health in humans. To find new chemical structures that extend lifespan, we screened 30 000 synthetic, diverse drug-like chemicals in Caenorhabditis elegans and identified several structurally related compounds that acted through DR mechanisms. The most potent of these NP1 impinges upon a food perception pathway by promoting glutamate signaling in the pharynx. This results in the overriding of a GPCR pathway involved in the perception of food and which normally acts to decrease glutamate signals. Our results describe the activation of a dietary restriction response through the pharmacological masking of a novel sensory pathway that signals the presence of food. This suggests that primary sensory pathways may represent novel targets for human pharmacology.
Model organisms subject to dietary restriction (DR) generally live longer. Accompanying this lifespan extension are improvements in overall health, based on multiple metrics. This indicates that pharmacological treatments that mimic the effects of DR could improve health in humans. To find new chemical structures that extend lifespan, we screened 30 000 synthetic, diverse drug-like chemicals in Caenorhabditis elegans and identified several structurally related compounds that acted through DR mechanisms. The most potent of these NP1 impinges upon a food perception pathway by promoting glutamate signaling in the pharynx. This results in the overriding of a GPCR pathway involved in the perception of food and which normally acts to decrease glutamate signals. Our results describe the activation of a dietary restriction response through the pharmacological masking of a novel sensory pathway that signals the presence of food. This suggests that primary sensory pathways may represent novel targets for human pharmacology.Model organisms subject to dietary restriction (DR) generally live longer. Accompanying this lifespan extension are improvements in overall health, based on multiple metrics. This indicates that pharmacological treatments that mimic the effects of DR could improve health in humans. To find new chemical structures that extend lifespan, we screened 30 000 synthetic, diverse drug-like chemicals in Caenorhabditis elegans and identified several structurally related compounds that acted through DR mechanisms. The most potent of these NP1 impinges upon a food perception pathway by promoting glutamate signaling in the pharynx. This results in the overriding of a GPCR pathway involved in the perception of food and which normally acts to decrease glutamate signals. Our results describe the activation of a dietary restriction response through the pharmacological masking of a novel sensory pathway that signals the presence of food. This suggests that primary sensory pathways may represent novel targets for human pharmacology.
Model organisms subject to dietary restriction ( DR ) generally live longer. Accompanying this lifespan extension are improvements in overall health, based on multiple metrics. This indicates that pharmacological treatments that mimic the effects of DR could improve health in humans. To find new chemical structures that extend lifespan, we screened 30 000 synthetic, diverse drug‐like chemicals in Caenorhabditis elegans and identified several structurally related compounds that acted through DR mechanisms. The most potent of these NP 1 impinges upon a food perception pathway by promoting glutamate signaling in the pharynx. This results in the overriding of a GPCR pathway involved in the perception of food and which normally acts to decrease glutamate signals. Our results describe the activation of a dietary restriction response through the pharmacological masking of a novel sensory pathway that signals the presence of food. This suggests that primary sensory pathways may represent novel targets for human pharmacology.
Summary Model organisms subject to dietary restriction (DR) generally live longer. Accompanying this lifespan extension are improvements in overall health, based on multiple metrics. This indicates that pharmacological treatments that mimic the effects of DR could improve health in humans. To find new chemical structures that extend lifespan, we screened 30 000 synthetic, diverse drug‐like chemicals in Caenorhabditis elegans and identified several structurally related compounds that acted through DR mechanisms. The most potent of these NP1 impinges upon a food perception pathway by promoting glutamate signaling in the pharynx. This results in the overriding of a GPCR pathway involved in the perception of food and which normally acts to decrease glutamate signals. Our results describe the activation of a dietary restriction response through the pharmacological masking of a novel sensory pathway that signals the presence of food. This suggests that primary sensory pathways may represent novel targets for human pharmacology.
Audience Academic
Author Garrett, Theo
Hughes, Robert E.
Lithgow, Gordon J.
Miller, Aaron
Lucanic, Mark
Yu, Ivan
Asadi Shahmirzadi, Azar
Holden‐Dye, Lindy
Gill, Matthew S.
Calahorro, Fernando
AuthorAffiliation 3 Center for Biological Sciences Institute for Life Sciences University of Southampton Southampton UK
4 Davis School of Gerontology University of Southern California Los Angeles CA USA
1 Buck Institute for Research on Aging 8001 Redwood Boulevard Novato CA USA
2 Dominican University of California 50 Acacia Avenue San Rafael CA USA
5 Department of Metabolism & Aging The Scripps Research Institute‐Scripps Florida 130 Scripps Way Jupiter FL 33458
AuthorAffiliation_xml – name: 1 Buck Institute for Research on Aging 8001 Redwood Boulevard Novato CA USA
– name: 3 Center for Biological Sciences Institute for Life Sciences University of Southampton Southampton UK
– name: 4 Davis School of Gerontology University of Southern California Los Angeles CA USA
– name: 2 Dominican University of California 50 Acacia Avenue San Rafael CA USA
– name: 5 Department of Metabolism & Aging The Scripps Research Institute‐Scripps Florida 130 Scripps Way Jupiter FL 33458
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Copyright 2016 The Authors. published by the Anatomical Society and John Wiley & Sons Ltd.
2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
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Copyright © 2016 The Anatomical Society and John Wiley & Sons Ltd
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Issue 5
Keywords Aging
Caenorhabditis
Pharmacogenetics
Drug Discovery
dietary restriction
Language English
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2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
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Snippet Summary Model organisms subject to dietary restriction (DR) generally live longer. Accompanying this lifespan extension are improvements in overall health,...
Model organisms subject to dietary restriction (DR) generally live longer. Accompanying this lifespan extension are improvements in overall health, based on...
Summary Model organisms subject to dietary restriction (DR) generally live longer. Accompanying this lifespan extension are improvements in overall health,...
Model organisms subject to dietary restriction ( DR ) generally live longer. Accompanying this lifespan extension are improvements in overall health, based on...
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StartPage 832
SubjectTerms Aging
Animals
Caenorhabditis
Caenorhabditis elegans - physiology
Caenorhabditis elegans Proteins - metabolism
Caloric Restriction
Chloride Channels - metabolism
dietary restriction
Drug Discovery
Feeding Behavior - drug effects
Food Deprivation - physiology
Glutamate
Glutamates - metabolism
Health aspects
Longevity - drug effects
Longevity - physiology
Models, Biological
Muscle Contraction - drug effects
Mutation - genetics
Neurophysiology
Original
Pharmacogenetics
Pharynx - drug effects
Pharynx - physiology
Receptors, Muscarinic - genetics
Receptors, Muscarinic - metabolism
Signal Transduction - drug effects
Small Molecule Libraries - analysis
Small Molecule Libraries - chemistry
Small Molecule Libraries - pharmacology
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Title Chemical activation of a food deprivation signal extends lifespan
URI https://onlinelibrary.wiley.com/doi/abs/10.1111%2Facel.12492
https://www.ncbi.nlm.nih.gov/pubmed/27220516
https://www.proquest.com/docview/1816998264
https://www.proquest.com/docview/1817837385
https://pubmed.ncbi.nlm.nih.gov/PMC5013014
Volume 15
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