title: Longevity manipulations differentially affect serotonin/dopamine level and behavioral deterioration in aging Caenorhabditis elegans.
abstract: Aging is accompanied with behavioral and cognitive decline. Changes in the neurotransmitter level are associated with the age-related behavioral deterioration, but whether well-known longevity manipulations affect the function of neurotransmitter system in aging animals is largely unclear. Here we report that serotonin (5-HT) and dopamine (DA) level decrease with age in C. elegans. The reduction results in downregulation of the activity of neurons controlled by 5-HT/DA signaling, and deterioration of some important behaviors, including pharyngeal pumping, food-induced slowing responses, and male mating. Longevity manipulations differentially affect the age-related decline in neuronal level of 5-HT/DA. The reduction and resultant behavioral deterioration occur in long-lived worms with defective insulin signaling [daf-2(e1370), age-1(hx546)] or mitochondria function [isp-1(qm150), tpk-1(qm162)], but not in long-lived worms with dietary restriction eat-2(ad1116). A reduced expression level of dopa decarboxylase BAS-1, the shared enzyme for 5-HT/DA synthesis, is responsible for the decline in 5-HT/DA levels. RNAi assay revealed that the sustained 5-HT/DA level in neurons of aged eat-2(ad1116) worms requires PHA-4 and its effectors superoxide dismutases and catalases, suggesting the involvement of reactive oxygen species in the 5-HT/DA decline. Furthermore, we found that elevating 5-HT/DA ameliorates age-related deterioration of pharyngeal pumping, food-induced slowing responses, and male mating in both wild-type and daf-2(e1370) worms. Together, dietary restriction preserves healthy behaviors in aged worms at least partially by sustaining a high 5-HT/DA level, and elevating the 5-HT/DA level in wild-type and daf-2(e1370) worms improves their behaviors during aging.
authors.affiliation: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China, and University of Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Jiang-An
authors.initials: JA
authors.lastname: Yin
authors.forename: Xi-Juan
authors.initials: XJ
authors.lastname: Liu
authors.forename: Jie
authors.initials: J
authors.lastname: Yuan
authors.forename: Jing
authors.initials: J
authors.lastname: Jiang
authors.forename: Shi-Qing
authors.initials: SQ
authors.lastname: Cai
mesh_terms: D000375:Aging / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D004298:Dopamine / Q000172:deficiency / Q000378:metabolism*; D057850:Hermaphroditic Organisms; D008136:Longevity / Q000502:physiology; D008297:Male; D023421:Models, Animal; D009424:Nervous System Physiological Phenomena / Q000502:physiology; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D012701:Serotonin / Q000172:deficiency / Q000378:metabolism*; D012726:Sexual Behavior, Animal / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
chemical_list: D029742:Caenorhabditis elegans Proteins; D012701:Serotonin; D004298:Dopamine