A cross-sectional twin study of 500 pairs of same-sexed twins with equal numbers of monozygotic (MZ) and dizygotic (DZ) and equal numbers of male and female twins in three age groups: early adulthood (100 pairs aged 25 to 35 years), middle adulthood (100 pairs aged 40 to 55 years), and late adulthood (300 pairs aged 60 years and older) will be undertaken to determine a) the extent to which genetic and environmental factors contribute to the significant observed variability among the elderly, and b) whether the importance of genetic factors decreases, and the importance of environmental factors increases, with age. Participants are identified from birth records maintained by the State of Minnesota and their current status determined using public records. Once contracted, twins will be asked to participate in a 6 hour in-home assessment of selected psychological, medical, and biological variables previously implicated in the normal aging process. The major dependent variables include; i) cognitive functioning, ii) personality and leisure-time interests, iii) simple and choice reaction time and iv) physical markers of aging such as pulmonary functioning, fasting glucose tolerance, grip strength and blood pressure. In addition, blood will be drawn on 40% of the sample and levels of DNA damage and DNA repair capability evaluated including; i) characterization of G-banded chromosomal breaks and rearrangements, ii) baseline and mutagen induced sister chromatid exchange (SCE) rates, iii) measures of DNA repair including UDS and O6 methyl-transferase (by collaborator R. Setlow) and iv) point mutation rates at the HPRT and Glycophorin A loci (by collaborators R. Albertini and R. Jensen). The in- home assessment also includes a detailed structured interview aimed at measuring those environmental/lifestyle factors hypothesized as relevant to the aging process including measures of i) diet, ii) physical activity, iii) intellectual activity, iv) social activity, and v) environmental exposure to mutagens. The proposed continuation will allow us to expand upon several significant findings including; i) an increase of stable chromosomal rearrangement with age, ii) an increase in induced but not baseline SCE rates with age, iii) significant heritability for many of the assessed measures, iv) a preliminary observation that heritability declines with age, and v) significant within person and cross-twin correlations between lifestyle factors and psychological functioning. In particular, data from the project will be analyzed to; i) identify cross-sectional age differences in DNA damage and repair capability, ii) estimate the proportion of phenotypic variance due to genetic and environmental factors and determine whether these variance components vary with age, and iii) identify the role played by specific environmental/lifestyle factors such as mutagen exposure in the case of DNA damage and intellectual activity in the case of cognitive functioning.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
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Mammalian Genetics Study Section (MGN)
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University of Minnesota Twin Cities
Schools of Arts and Sciences
United States
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Reynolds, Chandra A; Gatz, Margaret; Christensen, Kaare et al. (2016) Gene-Environment Interplay in Physical, Psychological, and Cognitive Domains in Mid to Late Adulthood: Is APOE a Variability Gene? Behav Genet 46:4-19
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