DRD4 genotype predicts longevity in mouse and human

• Autores: Grady, Deborah L.; Thanos, Panayotis K.; Corrada, Maria M.; Barnett Jr., Jeffrey C.; Ciobanu, Valentina; Shustarovich, Diana; Napoli, Anthony; Moyzis, Alexandra G.; Grandy, David; Rubinstein, Marcelo; Wang, Gene-Jack; Kawas, Claudia H.; Chen, Chuansheng; Dong, Qi; Wang, Eric; Volkow, Nora D.; Moyzis, Robert K.
• Año de publicación: 2013
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: Dopamina; Receptor D4; Longevidad
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

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.
Fil: Grady, Deborah L.. University of California. College of Medicine. Department of Biological Chemistry; Estados Unidos
Fil: Thanos, Panayotis K.. National Institute on Alcohol Abuse and Alcoholism. Laboratory of Neuroimaging; Estados Unidos. Brookhaven National Laboratory. Medical Department. Behavioral Neuropharmocology and Neuroimaging Laboratory; Estados Unidos. Stony Brook University. Department of Psychology; Estados Unidos
Fil: Corrada, Maria M.. University of California. Department of Neurology; Estados Unidos
Fil: Barnett Jr., Jeffrey C.. Brookhaven National Laboratory. Medical Department. Behavioral Neuropharmocology and Neuroimaging Laboratory; Estados Unidos
Fil: Ciobanu, Valentina. University of California. College of Medicine. Department of Biological Chemistry; Estados Unidos
Fil: Shustarovich, Diana. Brookhaven National Laboratory. Medical Department. Behavioral Neuropharmocology and Neuroimaging Laboratory; Estados Unidos
Fil: Napoli, Anthony. Brookhaven National Laboratory. Medical Department. Behavioral Neuropharmocology and Neuroimaging Laboratory; Estados Unidos
Fil: Moyzis, Alexandra G.. University of California. College of Medicine. Department of Biological Chemistry; Estados Unidos
Fil: Grandy, David. Oregon Health Sciences University. Physiology and Pharmacology; Estados Unidos
Fil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; Argentina
Fil: Wang, Gene-Jack. Brookhaven National Laboratory. Medical Department. Behavioral Neuropharmocology and Neuroimaging Laboratory; Estados Unidos
Fil: Kawas, Claudia H.. University of California. Department of Neurology; Estados Unidos
Fil: Chen, Chuansheng. University of California. Department of Psychology and Social Behavior; Estados Unidos
Fil: Dong, Qi. Beijing Normal University. National Key Laboratory of Cognitive Neuroscience and Learning; China
Fil: Wang, Eric. University of California. College of Medicine. Department of Biological Chemistry; Estados Unidos. Aria Diagnostics Inc.; Estados Unidos. University of California. Institute of Genomics and Bioinformatics; Estados Unidos
Fil: Volkow, Nora D.. National Institute on Alcohol Abuse and Alcoholism. Laboratory of Neuroimaging; Estados Unidos. Brookhaven National Laboratory. Medical Department. Behavioral Neuropharmocology and Neuroimaging Laboratory; Estados Unidos. National Institute on Drug Abuse; Estados Unidos
Fil: Moyzis, Robert K.. University of California. College of Medicine. Department of Biological Chemistry; Estados Unidos. Beijing Normal University. National Key Laboratory of Cognitive Neuroscience and Learning; China. University of California. Institute of Genomics and Bioinformatics; Estados Unidos