RRC ID 45630
Author Rangaraju S, Solis GM, Andersson SI, Gomez-Amaro RL, Kardakaris R, Broaddus CD, Niculescu AB 3rd, Petrascheck M.
Title Atypical antidepressants extend lifespan of Caenorhabditis elegans by activation of a non-cell-autonomous stress response.
Journal Aging Cell
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.
Volume 14(6)
Pages 971-81
Published 2015-12
DOI 10.1111/acel.12379
PMID 26255886
PMC PMC4693466
MeSH Aging / drug effects* Aging / physiology Animals Antidepressive Agents, Second-Generation / pharmacology* Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / metabolism Catalase / metabolism Fluoxetine / pharmacology Histamine H1 Antagonists / pharmacology Life Expectancy* Longevity / drug effects* Longevity / physiology Mianserin / analogs & derivatives Mianserin / pharmacology Oxidative Stress / drug effects* Peroxiredoxins / metabolism Reactive Oxygen Species / metabolism Serotonin Antagonists / pharmacology Serotonin Uptake Inhibitors / pharmacology Superoxide Dismutase / metabolism Synaptic Transmission / drug effects
IF 7.627
Times Cited 2
C.elegans tm776 tm760 tm1146