Longevity manipulations differentially affect serotonin/dopamine level and behavioral deterioration in aging Caenorhabditis elegans

J Neurosci. 2014 Mar 12;34(11):3947-58. doi: 10.1523/JNEUROSCI.4013-13.2014.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism*
  • Aging / physiology
  • Animals
  • Behavior, Animal / physiology
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / metabolism
  • Dopamine / deficiency
  • Dopamine / metabolism*
  • Hermaphroditic Organisms
  • Longevity / physiology
  • Male
  • Models, Animal
  • Nervous System Physiological Phenomena / physiology
  • Neurons / metabolism*
  • Neurons / physiology
  • Oxidative Stress / physiology
  • Serotonin / deficiency
  • Serotonin / metabolism*
  • Sexual Behavior, Animal / physiology
  • Signal Transduction / physiology


  • Caenorhabditis elegans Proteins
  • Serotonin
  • Dopamine