title: Interaction Between the FOXO1A-209 Genotype and Tea Drinking Is Significantly Associated with Reduced Mortality at Advanced Ages.
abstract: On the basis of the genotypic/phenotypic data from Chinese Longitudinal Healthy Longevity Survey (CLHLS) and Cox proportional hazard model, the present study demonstrates that interactions between carrying FOXO1A-209 genotypes and tea drinking are significantly associated with lower risk of mortality at advanced ages. Such a significant association is replicated in two independent Han Chinese CLHLS cohorts (p = 0.028-0.048 in the discovery and replication cohorts, and p = 0.003-0.016 in the combined dataset). We found the associations between tea drinking and reduced mortality are much stronger among carriers of the FOXO1A-209 genotype compared to non-carriers, and drinking tea is associated with a reversal of the negative effects of carrying FOXO1A-209 minor alleles, that is, from a substantially increased mortality risk to substantially reduced mortality risk at advanced ages. The impacts are considerably stronger among those who carry two copies of the FOXO1A minor allele than those who carry one copy. On the basis of previously reported experiments on human cell models concerning FOXO1A-by-tea-compounds interactions, we speculate that results in the present study indicate that tea drinking may inhibit FOXO1A-209 gene expression and its biological functions, which reduces the negative impacts of FOXO1A-209 gene on longevity (as reported in the literature) and offers protection against mortality risk at oldest-old ages. Our empirical findings imply that the health outcomes of particular nutritional interventions, including tea drinking, may, in part, depend upon individual genetic profiles, and the research on the effects of nutrigenomics interactions could potentially be useful for rejuvenation therapies in the clinic or associated healthy aging intervention programs.
authors.affiliation: 1 Center for the Study of Aging and Human Development and Geriatrics Division, Medical School of Duke University , Durham, North Carolina.|2 Center for Healthy Aging and Development Studies, National School of Development, Peking University , Beijing, China .
authors.forename: Yi
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: 1 Center for the Study of Aging and Human Development and Geriatrics Division, Medical School of Duke University , Durham, North Carolina.|3 Department of Management, Business School of Xiangtan University , Xiangtan, China .
authors.forename: Huashuai
authors.initials: H
authors.lastname: Chen
authors.affiliation: 4 State Key Laboratory of Genetics Engineering & MOE Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University , Shanghai, China .
authors.forename: Ting
authors.initials: T
authors.lastname: Ni
authors.affiliation: 5 Department of Agriculture Economics. Renmin University of China , Beijing, China .
authors.forename: Rongping
authors.initials: R
authors.lastname: Ruan
authors.affiliation: 6 Beijing Genomics Institute (BGI)-Shenzhen , Shenzhen, China .
authors.forename: Chao
authors.initials: C
authors.lastname: Nie
authors.affiliation: 6 Beijing Genomics Institute (BGI)-Shenzhen , Shenzhen, China .
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Liu
authors.affiliation: 7 Department of Psychological Medicine, National University of Singapore , Singapore .
authors.forename: Lei
authors.initials: L
authors.lastname: Feng
authors.affiliation: 8 Lieber Institute for Brain Development, Johns Hopkins University , Baltimore, Maryland.
authors.forename: Fengyu
authors.initials: F
authors.lastname: Zhang
authors.affiliation: 9 Department of Sociology, Peking University , Beijing, China .
authors.forename: Jiehua
authors.initials: J
authors.lastname: Lu
authors.affiliation: 9 Department of Sociology, Peking University , Beijing, China .
authors.forename: Jianxin
authors.initials: J
authors.lastname: Li
authors.affiliation: 10 Department of Human Population Genetics, Institute of Molecular Medicine, Peking University , Beijing, China .
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: 11 School of Life Sciences, Peking University , Beijing, China .
authors.forename: Wei
authors.initials: W
authors.lastname: Tao
authors.affiliation: 12 Duke Molecular Physiology Institute, Duke University , Durham, North Carolina.
authors.forename: Simon G
authors.initials: SG
authors.lastname: Gregory
authors.affiliation: 13 Department of Neurology, Medical Center, Duke University , Durham, North Carolina.
authors.forename: William
authors.initials: W
authors.lastname: Gottschalk
authors.affiliation: 13 Department of Neurology, Medical Center, Duke University , Durham, North Carolina.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Lutz
authors.affiliation: 14 Population Research Institute, Duke University , Durham, North Carolina.
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Land
authors.affiliation: 14 Population Research Institute, Duke University , Durham, North Carolina.
authors.forename: Anatoli
authors.initials: A
authors.lastname: Yashin
authors.affiliation: 15 Biostatistics and Biodemography, Institute of Public Health, University of Southern Denmark , Odense, Denmark .
authors.forename: Qihua
authors.initials: Q
authors.lastname: Tan
authors.affiliation: 16 National Institute of Geriatrics, Beijing Hospital , Ministry of Health of China, Beijing, China .
authors.forename: Ze
authors.initials: Z
authors.lastname: Yang
authors.affiliation: 6 Beijing Genomics Institute (BGI)-Shenzhen , Shenzhen, China .|17 Department of Biomedicine, Aarhus University , Aarhus, Denmark .
authors.forename: Lars
authors.initials: L
authors.lastname: Bolund
authors.affiliation: 6 Beijing Genomics Institute (BGI)-Shenzhen , Shenzhen, China .|18 Center for Genetic & Genomic Medicine, Zhejiang University School of Medicine , Hangzhou, China .
authors.forename: Qi
authors.initials: Q
authors.lastname: Ming
authors.affiliation: 6 Beijing Genomics Institute (BGI)-Shenzhen , Shenzhen, China .|19 James D. Watson Institute of Genome Sciences , Hangzhou, China .|20 Princess Al-Jawhara Centre of Excellence in Research of Hereditary Disorders, King Abdulaziz University , Jeddah, Saudi Arabia .
authors.forename: Huanming
authors.initials: H
authors.lastname: Yang
authors.affiliation: 21 School of Medicine, Zhejiang University , Hangzhou, China .
authors.forename: Junxia
authors.initials: J
authors.lastname: Min
authors.affiliation: 22 Department of Human Welfare, Okinawa International University , Ginowan, Japan .|23 Department of Research, Kuakini Medical Center and Department of Geriatric Medicine, John A. Burns School of Medicine, University of Hawaii , Hawaii.
authors.forename: D Craig
authors.initials: DC
authors.lastname: Willcox
authors.affiliation: 23 Department of Research, Kuakini Medical Center and Department of Geriatric Medicine, John A. Burns School of Medicine, University of Hawaii , Hawaii.
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Willcox
authors.affiliation: 11 School of Life Sciences, Peking University , Beijing, China .
authors.forename: Jun
authors.initials: J
authors.lastname: Gu
authors.affiliation: 12 Duke Molecular Physiology Institute, Duke University , Durham, North Carolina.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hauser
authors.affiliation: 10 Department of Human Population Genetics, Institute of Molecular Medicine, Peking University , Beijing, China .
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Tian
authors.affiliation: 24 Max Planck Institute for Demographic Research , Rostock, Germany .
authors.forename: James W
authors.initials: JW
authors.lastname: Vaupel
mesh_terms: D000367:Age Factors; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D002423:Cause of Death; D002681:China; D005260:Female; D000071161:Forkhead Box Protein O1 / Q000235:genetics*; D005787:Gene Frequency; D059647:Gene-Environment Interaction; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D010641:Phenotype; D065840:Protective Factors; D018570:Risk Assessment; D012307:Risk Factors; D016019:Survival Analysis
chemical_list: C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1