Research Plan of the Overall Program We are currently engaged in a four-year program f research that focuses on the Fries hypothesis, i.e., whether genetic factors limit human life expectancy to 85 years or so. We request five years of continued support for broader research on oldest-old mortality. The overarching theme of the proposed program of research is """"""""Trajectories of Mortality at Advanced Ages"""""""". We will address four main issues concerning trajectories of mortality at advanced ages: (i) the environmental and genetic plasticity of mortality rates, (ii) the deceleration of mortality with age, (iii) the interrelationship between disability (ADL's) and mortality, and (iv) male-female differences. To do so: (1) Four the benefit of other researchers we will gather, code, verify, archive, and release public-use files of data on mortality rates and various covariates (such as causes of death and ADL's) for various populations, including males and females in the United States and 27 other countries in recent decades, MZ twins and both same-sex and different-sex DZ twins born in Denmark between 1870 and 1930, and three related fruit-fly species as well as inbred lines of Drosophila. (2) We will use demographic and statistical methods (including life- table, extinct-cohort, smoothing, and survival-analysis methods) to summarize the data and describe trajectories of mortality at advanced ages, including analysis of how mortality rates change with age, over time, for successive birth cohorts, across different countries, across different areas of the United States, for males vs. females, for different causes of death (for Danish twins), at different ADL levels, for different species, for different genotypes, and for population (of Drosophila) that share different chromosomal regions (quantitative trait loci). (3) We will develop alternative theory-based models that incorporate biological knowledge and fit them to the data to gain a understanding of aging and mortality. The models will include genetic and environmental factors, mortality trajectories for individuals, and mortality selection in heterogeneous populations. (4) We will develop demographic and statistical methods of analysis useful for describing the data and analyzing underlying mechanisms as well as biological methods of experimental demography and quantitative trait locus analysis. In particular, we will develop extinct-cohort methods; Lexis-map methods; experimental demography methods for studying ADL's and mortality under different conditions, adaptations of methods of quantitative trait locus analysis for classifying individual Drosophila according to chromosomal regions, models; to simultaneously fit mortality data for the oldest-old in various cohorts, countries, areas of the United States, and species; models to simultaneously analyze mortality data on the general populations of Denmark as well as the MZ and DZ twin population; multivariate stochastic process models to combine mortality data with ADL data, both for Danish twins and for the Medflies and Drosophila, and GoM models of the dynamics of death and disability in the insect experiments.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG008761-06
Application #
2050374
Study Section
Special Emphasis Panel (ZAG1-CAG-7 (07))
Project Start
1990-02-01
Project End
1998-12-31
Budget Start
1995-03-25
Budget End
1995-12-31
Support Year
6
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Duke University
Department
Type
Organized Research Units
DUNS #
071723621
City
Durham
State
NC
Country
United States
Zip Code
27705
Debrabant, Birgit; Soerensen, Mette; Christiansen, Lene et al. (2018) DNA methylation age and perceived age in elderly Danish twins. Mech Ageing Dev 169:40-44
Dato, Serena; Soerensen, Mette; De Rango, Francesco et al. (2018) The genetic component of human longevity: New insights from the analysis of pathway-based SNP-SNP interactions. Aging Cell 17:e12755
Svane, Anne Marie; Soerensen, Mette; Lund, Jesper et al. (2018) DNA Methylation and All-Cause Mortality in Middle-Aged and Elderly Danish Twins. Genes (Basel) 9:
Jensen, Magnus T; Wod, Mette; Galatius, Søren et al. (2018) Heritability of resting heart rate and association with mortality in middle-aged and elderly twins. Heart 104:30-36
Pahlen, Shandell; Hamdi, Nayla R; Dahl Aslan, Anna K et al. (2018) Age-Moderation of Genetic and Environmental Contributions to Cognitive Functioning in Mid- and Late-Life for Specific Cognitive Abilities. Intelligence 68:70-81
Mengel-From, Jonas; Rønne, Mette E; Carlsen, Anting L et al. (2018) Circulating, Cell-Free Micro-RNA Profiles Reflect Discordant Development of Dementia in Monozygotic Twins. J Alzheimers Dis 63:591-601
Saunders, Gretchen R B; Elkins, Irene J; Christensen, Kaare et al. (2018) The relationship between subjective well-being and mortality within discordant twin pairs from two independent samples. Psychol Aging 33:439-447
Pedersen, Jacob K; Elo, Irma T; Schupf, Nicole et al. (2017) The Survival of Spouses Marrying Into Longevity-Enriched Families. J Gerontol A Biol Sci Med Sci 72:109-114
Flachsbart, Friederike; Dose, Janina; Gentschew, Liljana et al. (2017) Identification and characterization of two functional variants in the human longevity gene FOXO3. Nat Commun 8:2063
Fagan, Erin; Sun, Fangui; Bae, Harold et al. (2017) Telomere length is longer in women with late maternal age. Menopause 24:497-501

Showing the most recent 10 out of 445 publications