title: Atypical antidepressants extend lifespan of Caenorhabditis elegans by activation of a non-cell-autonomous stress response.
abstract: Oxidative stress has long been associated with aging and has recently been linked to psychiatric disorders, including psychosis and depression. We identified multiple antipsychotics and antidepressants that extend Caenorhabditis elegans lifespan and protect the animal from oxidative stress. Here, we report that atypical antidepressants activate a neuronal mechanism that regulates the response to oxidative stress throughout the animal. While the activation of the oxidative stress response by atypical antidepressants depends on synaptic transmission, the activation by reactive oxygen species does not. Lifespan extension by atypical antidepressants depends on the neuronal oxidative stress response activation mechanism. Neuronal regulation of the oxidative stress response is likely to have evolved as a survival mechanism to protect the organism from oxidative stress, upon detection of adverse or dangerous conditions by the nervous system.
authors.affiliation: Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA, USA.|Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, USA.|Department of Molecular and Cellular Neuroscience, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Sunitha
authors.initials: S
authors.lastname: Rangaraju
authors.affiliation: Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA, USA.|Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, USA.|Department of Molecular and Cellular Neuroscience, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Solis
authors.affiliation: Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Sofia I
authors.initials: SI
authors.lastname: Andersson
authors.affiliation: Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA, USA.|Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, USA.|Department of Molecular and Cellular Neuroscience, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Rafael L
authors.initials: RL
authors.lastname: Gomez-Amaro
authors.affiliation: Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Rozina
authors.initials: R
authors.lastname: Kardakaris
authors.affiliation: Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA, USA.|Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, USA.|Department of Molecular and Cellular Neuroscience, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Caroline D
authors.initials: CD
authors.lastname: Broaddus
authors.affiliation: Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Alexander B
authors.initials: AB
authors.lastname: Niculescu
authors.affiliation: Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA, USA.|Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, USA.|Department of Molecular and Cellular Neuroscience, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Petrascheck
mesh_terms: D000375:Aging / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D005473:Fluoxetine / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D008017:Life Expectancy; D008136:Longevity / Q000187:drug effects* / Q000502:physiology; D008803:Mianserin / Q000031:analogs & derivatives / Q000494:pharmacology; D000078785:Mirtazapine; D018384:Oxidative Stress / Q000187:drug effects*; D054464:Peroxiredoxins / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D018687:Antidepressive Agents, Second-Generation; D029742:Caenorhabditis elegans Proteins; D002374:Catalase; D005473:Fluoxetine; D006634:Histamine H1 Antagonists; D008803:Mianserin; D000078785:Mirtazapine; D054464:Peroxiredoxins; D017382:Reactive Oxygen Species; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; D013482:Superoxide Dismutase; C534226:PRDX-2 protein, C elegans; C587809:Sod-1 protein, C elegans
keywords: Caenorhabditis elegans; anti-aging; antidepressant; non-cell-autonomous; psychiatric disease; signal transduction; stress; synaptic transmission