GABA receptors differentially regulate life span and health span in C. elegans through distinct downstream mechanisms. 2019

Fengling Yuan, and Jiejun Zhou, and Lingxiu Xu, and Wenxin Jia, and Lei Chun, and X Z Shawn Xu, and Jianfeng Liu
International Research Center for Sensory Biology and Technology of Ministry of Science and Technology, Key Laboratory of Molecular Biophysics of Ministry of Education, and College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.

GABA, a prominent inhibitory neurotransmitter, is best known to regulate neuronal functions in the nervous system. However, much less is known about the role of GABA signaling in other physiological processes. Interestingly, recent work showed that GABA signaling can regulate life span via a metabotropic GABAB receptor in Caenorhabditis elegans. However, the role of other types of GABA receptors in life span has not been clearly defined. It is also unclear whether GABA signaling regulates health span. Here, using C. elegans as a model, we systematically interrogated the role of various GABA receptors in both life span and health span. We find that mutations in four different GABA receptors extend health span by promoting resistance to stress and pathogen infection and that two such receptor mutants also show extended life span. Different GABA receptors engage distinct transcriptional factors to regulate life span and health span, and even the same receptor regulates life span and health span via different transcription factors. Our results uncover a novel, profound role of GABA signaling in aging in C. elegans, which is mediated by different GABA receptors coupled to distinct downstream effectors.

UI MeSH Term Description Entries
D008136 Longevity The normal length of time of an organism's life. Length of Life,Life Span,Lifespan,Life Spans,Lifespans
D000375 Aging The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time. Senescence,Aging, Biological,Biological Aging
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D017173 Caenorhabditis elegans A species of nematode that is widely used in biological, biochemical, and genetic studies. Caenorhabditis elegan,elegan, Caenorhabditis
D018079 Receptors, GABA Cell-surface proteins that bind GAMMA-AMINOBUTYRIC ACID with high affinity and trigger changes that influence the behavior of cells. GABA-A receptors control chloride channels formed by the receptor complex itself. They are blocked by bicuculline and usually have modulatory sites sensitive to benzodiazepines and barbiturates. GABA-B receptors act through G-proteins on several effector systems, are insensitive to bicuculline, and have a high affinity for L-baclofen. GABA Receptors,Receptors, gamma-Aminobutyric Acid,gamma-Aminobutyric Acid Receptors,GABA Receptor,gamma-Aminobutyric Acid Receptor,Receptor, GABA,Receptor, gamma-Aminobutyric Acid,Receptors, gamma Aminobutyric Acid,gamma Aminobutyric Acid Receptor,gamma Aminobutyric Acid Receptors
D018384 Oxidative Stress A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). Anti-oxidative Stress,Antioxidative Stress,DNA Oxidative Damage,Nitro-Oxidative Stress,Oxidative Cleavage,Oxidative DNA Damage,Oxidative Damage,Oxidative Injury,Oxidative Nitrative Stress,Oxidative Stress Injury,Oxidative and Nitrosative Stress,Stress, Oxidative,Anti oxidative Stress,Anti-oxidative Stresses,Antioxidative Stresses,Cleavage, Oxidative,DNA Damage, Oxidative,DNA Oxidative Damages,Damage, DNA Oxidative,Damage, Oxidative,Damage, Oxidative DNA,Injury, Oxidative,Injury, Oxidative Stress,Nitrative Stress, Oxidative,Nitro Oxidative Stress,Nitro-Oxidative Stresses,Oxidative Cleavages,Oxidative DNA Damages,Oxidative Damage, DNA,Oxidative Damages,Oxidative Injuries,Oxidative Nitrative Stresses,Oxidative Stress Injuries,Oxidative Stresses,Stress Injury, Oxidative,Stress, Anti-oxidative,Stress, Antioxidative,Stress, Nitro-Oxidative,Stress, Oxidative Nitrative,Stresses, Nitro-Oxidative
D029742 Caenorhabditis elegans Proteins Proteins from the nematode species CAENORHABDITIS ELEGANS. The proteins from this species are the subject of scientific interest in the area of multicellular organism MORPHOGENESIS. C elegans Proteins
D030801 Animals, Genetically Modified ANIMALS whose GENOME has been altered by GENETIC ENGINEERING, or their offspring. Animals, Transgenic,Genetically Modified Animals,Transgenic Animals,Founder Animals, Transgenic,GMO Animals,Genetically Engineered Animals,Animal, GMO,Animal, Genetically Engineered,Animal, Genetically Modified,Animal, Transgenic,Animal, Transgenic Founder,Animals, GMO,Animals, Genetically Engineered,Animals, Transgenic Founder,Engineered Animal, Genetically,Engineered Animals, Genetically,Founder Animal, Transgenic,GMO Animal,Genetically Engineered Animal,Genetically Modified Animal,Modified Animal, Genetically,Modified Animals, Genetically,Transgenic Animal,Transgenic Founder Animal,Transgenic Founder Animals
D064113 CRISPR-Cas Systems Adaptive antiviral defense mechanisms, in archaea and bacteria, based on DNA repeat arrays called CLUSTERED REGULARLY INTERSPACED SHORT PALINDROMIC REPEATS (CRISPR elements) that function in conjunction with CRISPR-ASSOCIATED PROTEINS (Cas proteins). Several types have been distinguished, including Type I, Type II, and Type III, based on signature motifs of CRISPR-ASSOCIATED PROTEINS. CRISPR Cas Systems,CRISPR-Cas System,System, CRISPR-Cas,Systems, CRISPR-Cas

Related Publications

Fengling Yuan, and Jiejun Zhou, and Lingxiu Xu, and Wenxin Jia, and Lei Chun, and X Z Shawn Xu, and Jianfeng Liu
August 2023, Proceedings of the National Academy of Sciences of the United States of America,
Fengling Yuan, and Jiejun Zhou, and Lingxiu Xu, and Wenxin Jia, and Lei Chun, and X Z Shawn Xu, and Jianfeng Liu
December 2005, Science (New York, N.Y.),
Fengling Yuan, and Jiejun Zhou, and Lingxiu Xu, and Wenxin Jia, and Lei Chun, and X Z Shawn Xu, and Jianfeng Liu
August 2004, Science (New York, N.Y.),
Fengling Yuan, and Jiejun Zhou, and Lingxiu Xu, and Wenxin Jia, and Lei Chun, and X Z Shawn Xu, and Jianfeng Liu
January 1999, Neurobiology of aging,
Fengling Yuan, and Jiejun Zhou, and Lingxiu Xu, and Wenxin Jia, and Lei Chun, and X Z Shawn Xu, and Jianfeng Liu
July 2005, Cell metabolism,
Fengling Yuan, and Jiejun Zhou, and Lingxiu Xu, and Wenxin Jia, and Lei Chun, and X Z Shawn Xu, and Jianfeng Liu
January 2014, Age (Dordrecht, Netherlands),
Fengling Yuan, and Jiejun Zhou, and Lingxiu Xu, and Wenxin Jia, and Lei Chun, and X Z Shawn Xu, and Jianfeng Liu
November 2020, Geriatrics (Basel, Switzerland),
Fengling Yuan, and Jiejun Zhou, and Lingxiu Xu, and Wenxin Jia, and Lei Chun, and X Z Shawn Xu, and Jianfeng Liu
December 2016, Scientific reports,
Fengling Yuan, and Jiejun Zhou, and Lingxiu Xu, and Wenxin Jia, and Lei Chun, and X Z Shawn Xu, and Jianfeng Liu
February 2013, Cell stem cell,
Fengling Yuan, and Jiejun Zhou, and Lingxiu Xu, and Wenxin Jia, and Lei Chun, and X Z Shawn Xu, and Jianfeng Liu
May 2012, The journals of gerontology. Series A, Biological sciences and medical sciences,
Copied contents to your clipboard!