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Featured ArticleArticles, Behavioral/Cognitive

DRD4 Genotype Predicts Longevity in Mouse and Human

Deborah L. Grady, Panayotis K. Thanos, Maria M. Corrada, Jeffrey C. Barnett Jr., Valentina Ciobanu, Diana Shustarovich, Anthony Napoli, Alexandra G. Moyzis, David Grandy, Marcelo Rubinstein, Gene-Jack Wang, Claudia H. Kawas, Chuansheng Chen, Qi Dong, Eric Wang, Nora D. Volkow and Robert K. Moyzis
Journal of Neuroscience 2 January 2013, 33 (1) 286-291; DOI: https://doi.org/10.1523/JNEUROSCI.3515-12.2013
Deborah L. Grady
1Department of Biological Chemistry, College of Medicine, University of California, Irvine, California 92697,
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Panayotis K. Thanos
2Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, Maryland 20892,
3Behavioral Neuropharmocology and Neuroimaging Laboratory, Medical Department, Brookhaven National Laboratory, Upton, New York 11973,
4Department of Psychology, Stony Brook University, Stony Brook, New York 11794,
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Maria M. Corrada
5Department of Neurology, University of California, Orange, California 92868,
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Jeffrey C. Barnett Jr.
3Behavioral Neuropharmocology and Neuroimaging Laboratory, Medical Department, Brookhaven National Laboratory, Upton, New York 11973,
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Valentina Ciobanu
1Department of Biological Chemistry, College of Medicine, University of California, Irvine, California 92697,
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Diana Shustarovich
3Behavioral Neuropharmocology and Neuroimaging Laboratory, Medical Department, Brookhaven National Laboratory, Upton, New York 11973,
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Anthony Napoli
3Behavioral Neuropharmocology and Neuroimaging Laboratory, Medical Department, Brookhaven National Laboratory, Upton, New York 11973,
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Alexandra G. Moyzis
1Department of Biological Chemistry, College of Medicine, University of California, Irvine, California 92697,
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David Grandy
6Physiology and Pharmacology, Oregon Health Sciences University, Portland, Oregon, 97239,
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Marcelo Rubinstein
7Institute for Research on Genetic Engineering and Molecular Biology, National Council for Science and Technology (CONICET), C1428ADN Buenos Aires, Argentina,
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Gene-Jack Wang
3Behavioral Neuropharmocology and Neuroimaging Laboratory, Medical Department, Brookhaven National Laboratory, Upton, New York 11973,
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Claudia H. Kawas
5Department of Neurology, University of California, Orange, California 92868,
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Chuansheng Chen
8Department of Psychology and Social Behavior, University of California, Irvine, California 92697,
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Qi Dong
9National Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875, Peoples Republic of China,
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Eric Wang
1Department of Biological Chemistry, College of Medicine, University of California, Irvine, California 92697,
10Aria Diagnostics, Inc., San Jose, California 95138,
11Institute of Genomics and Bioinformatics, University of California, Irvine, California 92697, and
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Nora D. Volkow
2Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, Maryland 20892,
3Behavioral Neuropharmocology and Neuroimaging Laboratory, Medical Department, Brookhaven National Laboratory, Upton, New York 11973,
12National Institute on Drug Abuse, NIH, Bethesda, Maryland 20892
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Robert K. Moyzis
1Department of Biological Chemistry, College of Medicine, University of California, Irvine, California 92697,
9National Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875, Peoples Republic of China,
11Institute of Genomics and Bioinformatics, University of California, Irvine, California 92697, and
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Abstract

Longevity is influenced by genetic and environmental factors. The brain's dopamine system may be particularly relevant, since it modulates traits (e.g., sensitivity to reward, incentive motivation, sustained effort) that impact behavioral responses to the environment. In particular, the dopamine D4 receptor (DRD4) has been shown to moderate the impact of environments on behavior and health. We tested the hypothesis that the DRD4 gene influences longevity and that its impact is mediated through environmental effects. Surviving participants of a 30-year-old population-based health survey (N = 310; age range, 90–109 years; the 90+ Study) were genotyped/resequenced at the DRD4 gene and compared with a European ancestry-matched younger population (N = 2902; age range, 7–45 years). We found that the oldest-old population had a 66% increase in individuals carrying the DRD4 7R allele relative to the younger sample (p = 3.5 × 10−9), and that this genotype was strongly correlated with increased levels of physical activity. Consistent with these results, DRD4 knock-out mice, when compared with wild-type and heterozygous mice, displayed a 7–9.7% decrease in lifespan, reduced spontaneous locomotor activity, and no lifespan increase when reared in an enriched environment. These results support the hypothesis that DRD4 gene variants contribute to longevity in humans and in mice, and suggest that this effect is mediated by shaping behavioral responses to the environment.

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The Journal of Neuroscience: 33 (1)
Journal of Neuroscience
Vol. 33, Issue 1
2 Jan 2013
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DRD4 Genotype Predicts Longevity in Mouse and Human
Deborah L. Grady, Panayotis K. Thanos, Maria M. Corrada, Jeffrey C. Barnett Jr., Valentina Ciobanu, Diana Shustarovich, Anthony Napoli, Alexandra G. Moyzis, David Grandy, Marcelo Rubinstein, Gene-Jack Wang, Claudia H. Kawas, Chuansheng Chen, Qi Dong, Eric Wang, Nora D. Volkow, Robert K. Moyzis
Journal of Neuroscience 2 January 2013, 33 (1) 286-291; DOI: 10.1523/JNEUROSCI.3515-12.2013

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DRD4 Genotype Predicts Longevity in Mouse and Human
Deborah L. Grady, Panayotis K. Thanos, Maria M. Corrada, Jeffrey C. Barnett Jr., Valentina Ciobanu, Diana Shustarovich, Anthony Napoli, Alexandra G. Moyzis, David Grandy, Marcelo Rubinstein, Gene-Jack Wang, Claudia H. Kawas, Chuansheng Chen, Qi Dong, Eric Wang, Nora D. Volkow, Robert K. Moyzis
Journal of Neuroscience 2 January 2013, 33 (1) 286-291; DOI: 10.1523/JNEUROSCI.3515-12.2013
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