title: Metabotropic GABA signalling modulates longevity in C. elegans.
abstract: The nervous system plays an important but poorly understood role in modulating longevity. GABA, a prominent inhibitory neurotransmitter, is best known to regulate nervous system function and behaviour in diverse organisms. Whether GABA signalling affects aging, however, has not been explored. Here we examined mutants lacking each of the major neurotransmitters in C. elegans, and find that deficiency in GABA signalling extends lifespan. This pro-longevity effect is mediated by the metabotropic GABAB receptor GBB-1, but not ionotropic GABAA receptors. GBB-1 regulates lifespan through G protein-PLCβ signalling, which transmits longevity signals to the transcription factor DAF-16/FOXO, a key regulator of lifespan. Mammalian GABAB receptors can functionally substitute for GBB-1 in lifespan control in C. elegans. Our results uncover a new role of GABA signalling in lifespan regulation in C. elegans, raising the possibility that a similar process may occur in other organisms.
authors.affiliation: College of Life Science and Technology, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China.|Department of Molecular and Integrative Physiology, Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Chun
authors.affiliation: College of Life Science and Technology, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China.|Department of Molecular and Integrative Physiology, Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Jianke
authors.initials: J
authors.lastname: Gong
authors.affiliation: College of Life Science and Technology, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China.
authors.forename: Fengling
authors.initials: F
authors.lastname: Yuan
authors.affiliation: College of Life Science and Technology, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China.|Department of Molecular and Integrative Physiology, Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Bi
authors.initials: B
authors.lastname: Zhang
authors.affiliation: College of Life Science and Technology, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China.
authors.forename: Hongkang
authors.initials: H
authors.lastname: Liu
authors.affiliation: College of Life Science and Technology, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China.
authors.forename: Tianlin
authors.initials: T
authors.lastname: Zheng
authors.affiliation: College of Life Science and Technology, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China.
authors.forename: Teng
authors.initials: T
authors.lastname: Yu
authors.affiliation: Department of Molecular and Integrative Physiology, Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: X Z Shawn
authors.initials: XZ
authors.lastname: Xu
authors.affiliation: College of Life Science and Technology, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism; D019204:GTP-Binding Proteins; D008136:Longevity / Q000235:genetics*; D054799:Phospholipase C beta / Q000378:metabolism; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism; D018080:Receptors, GABA-B / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; C108831:daf-16 protein, C elegans; D005680:gamma-Aminobutyric Acid; D054799:Phospholipase C beta; D019204:GTP-Binding Proteins