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A Phenotyping Regimen for Genetically Modified Mice Used to Study Genes Implicated in Human Diseases of Aging
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DRD4 genotype predicts longevity in mouse and human.

Deborah L Grady1, Panayotis K Thanos, Maria M Corrada

  • 1Department of Biological Chemistry, College of Medicine, University of California, Irvine, California 92697, USA.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|January 4, 2013
PubMed
Summary
This summary is machine-generated.

The dopamine D4 receptor (DRD4) gene influences longevity by affecting behavior and environmental responses. Specific DRD4 gene variants are linked to longer lifespans in humans and mice.

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Area of Science:

  • Genetics
  • Neuroscience
  • Longevity research

Background:

  • Longevity is influenced by genetic and environmental factors.
  • The dopamine system, particularly the dopamine D4 receptor (DRD4), modulates behaviors impacting health and environmental responses.
  • DRD4 gene variants may moderate environmental influences on behavior and health outcomes.

Purpose of the Study:

  • To test the hypothesis that the DRD4 gene influences longevity.
  • To investigate if the DRD4 gene's impact on longevity is mediated by environmental effects.

Main Methods:

  • Genotyping and resequencing of the DRD4 gene in centenarians (90+ Study) and a younger population.
  • Comparison of DRD4 allele frequencies between oldest-old humans and a younger cohort.
  • Lifespan and behavioral analysis of DRD4 knock-out mice compared to wild-type and heterozygous controls in standard and enriched environments.

Main Results:

  • A significant increase (66%) in the DRD4 7R allele was observed in the oldest-old human population compared to the younger sample.
  • The DRD4 7R allele correlated with increased physical activity levels in humans.
  • DRD4 knock-out mice exhibited a 7-9.7% decrease in lifespan and reduced locomotor activity, with no lifespan extension in enriched environments.

Conclusions:

  • DRD4 gene variants contribute to longevity in both humans and mice.
  • The effect of DRD4 on longevity appears to be mediated by its role in shaping behavioral responses to the environment.