application): Until recently, mortality for nearly all species was believed to increase exponentially at older ages. Several reports have now shown that in humans, Drosophila, reedfiles, and nematodes mortality levels off and, in some instances, even declines at advanced ages. However, it is not yet clear whether the observed mortality patterns are due to a leveling off of the rate of senescence in each individual or to environmental or genetic heterogeneity within the population. Baker s yeast (Saccharomyces cerevisiae) is a highly studied unicellular fungus with a completely sequenced genome which shares remarkable similarities with human cells and has a lifespan of more than 30 days in stationary phase. These features and the established and straightforward genetic manipulations available make yeast a valuable model to study mortality trajectories in eukaryotes. The goal of this proposed research is to study the age-specific mortality of large populations of S. cerevisiae, to isolate long-lived mutants, and to establish whether this unicellular eukaryote undergoes age-dependent deteriorative physiological changes analogous to those seen in higher eukaryotes. The mortality and physiological changes for billions of organisms will be studied in a highly controlled environment and established yeast techniques will be used to isolate longlived mutanrs. These experiments will extend biodemographical studies to the fungal kingdom, will give further test to the hypothesis that mortality decelerates at advanced ages, and will provide insights on the mechanisms that determine longevity in lower as well as higher eukaryotes. The large size of the initial yeast population will allow the study of mortality patterns and the isolation of long-lived mutants when an exceedingly small fraction of the organisms are still alive.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG008761-12
Application #
6411204
Study Section
Project Start
2001-01-15
Project End
2001-12-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
12
Fiscal Year
2001
Total Cost
$389,479
Indirect Cost
Name
Duke University
Department
Type
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

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