Aging can be defined as progressive deterioration of various biological functions with gradual increase in the risk of disease and death. This phenomenon is very complex with both genetic and non-genetic factors in action. The heritability of human longevity is estimated to be somewhere between 0.15 and 0.35. The action of genetic contributors can be modified by environment, resulting in altered risk of aging. One fundamental task in understanding its etiology is dissecting the relative contributions of genetic and non-genetic factors. My long-term research interest lies in the hereditary aspect of human aging and how the manifestation of the genetic basis is influenced by non-genetic factors during the life history of individuals. Based on twin study designs, I plan to identify genetic and epigenetie risk factors involved in human aging. In principle, the genetic aspect of healthy aging in twins can be studied by investigating concordant dizygotic twins, and the eipgenetic aspect by investigating discordant monozygotic twins with appropropate controls. The genetic study is to test the hypothesis that long-lived family members share common genetic variants that contribute to longevity and healthy aging. The epigenettc study is to test the hypothesis that the environmental contribution to the phenotypic variation of healthy aging is mediated by epigenetie mechanisms. To achieve these goals, I propose four Specific Aims.
Aim 1 is to recruit twins who are at least 68 years old by means of the Mid-Attantic Twin Registry (MATR), which is currently the largest twin registry in the U. S. According to data recently provided by the MATR, there are over 700 twin pairs available for this study.
Aim 2 is to compile their healthy aging profiles and estimate their biological ages. For this purpose, we will survey participating twins for various health variables, which include medical history, physical and cognitive functioning.
Aim 3 is to identify genes associated with healthy aging and longevity. For this aim, we will first identify genomic regions linked to healthy aging. Next, we will fine map the regions by applying case-control association analysis.
Aim 4 is to establish DNA methylation as an epigenetie mechanim of healthy aging, and for this aim, we will study DNA methylation status of twins.

Public Health Relevance

Human aging is a complicated phenomenon with both genetic and environmental factors involved, and for better understanding of it, we need study designs that can address both aspects of aging. This research project using twins provides such an integrative approach, and the proposed research will advance our knowledge on healthy aging and may lead to interventins that will improve health in the elderly.

Agency
National Institute of Health (NIH)
Type
Exploratory Grants (P20)
Project #
5P20GM103629-03
Application #
8663296
Study Section
Special Emphasis Panel (ZRR1)
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Tulane University
Department
Type
DUNS #
City
New Orleans
State
LA
Country
United States
Zip Code
70118
Zhang, Yanqing; Fava, Genevieve E; Wang, Hongjun et al. (2016) PAX4 Gene Transfer Induces α-to-β Cell Phenotypic Conversion and Confers Therapeutic Benefits for Diabetes Treatment. Mol Ther 24:251-60
Burks, Hope E; Phamduy, Theresa B; Azimi, Mohammad S et al. (2016) Laser Direct-Write Onto Live Tissues: A Novel Model for Studying Cancer Cell Migration. J Cell Physiol 231:2333-8
Boraas, Liana C; Ahsan, Tabassum (2016) Lack of vimentin impairs endothelial differentiation of embryonic stem cells. Sci Rep 6:30814
Zhou, Xiang; Hao, Qian; Liao, Peng et al. (2016) Nerve growth factor receptor negates the tumor suppressor p53 as a feedback regulator. Elife 5:
Mock, Jeffrey R; Foundas, Anne L; Golob, Edward J (2016) Cortical activity during cued picture naming predicts individual differences in stuttering frequency. Clin Neurophysiol 127:3093-101
Yariswamy, Manjunath; Yoshida, Tadashi; Valente, Anthony J et al. (2016) Cardiac-restricted Overexpression of TRAF3 Interacting Protein 2 (TRAF3IP2) Results in Spontaneous Development of Myocardial Hypertrophy, Fibrosis, and Dysfunction. J Biol Chem 291:19425-36
Sloas, David C; Stewart, Scott A; Sweat, Richard S et al. (2016) Estimation of the Pressure Drop Required for Lymph Flow through Initial Lymphatic Networks. Lymphat Res Biol 14:62-9
Quijano, Lina M; Lynch, Kristen M; Allan, Christopher H et al. (2016) Looking Ahead to Engineering Epimorphic Regeneration of a Human Digit or Limb. Tissue Eng Part B Rev 22:251-62
Jiang, James C; Stumpferl, Stefan W; Tiwari, Anurag et al. (2016) Identification of the Target of the Retrograde Response that Mediates Replicative Lifespan Extension in Saccharomyces cerevisiae. Genetics 204:659-673
Wolfe, Russell P; Guidry, Julia B; Messina, Stephanie L et al. (2016) Applying Shear Stress to Pluripotent Stem Cells. Methods Mol Biol 1341:377-89

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