Project 6: Extreme Longevity in Nematodes: Genes & Environments This project will examine mortality and exceptional survival in the nematode Caenorhabditis elegans. Our overarching hypothesis is that longevity is extremely plastic. Corollaries of this hypothesis are that both genetic and environmental factors can work independently in specifying mortality. Moreover, mortality is controlled segmentally: reduced mortality at one age does not automatically cause similar changes in mortality at all ages. We have some evidence in favor of our main hypothesis and its corollaries but we are not at all sure whether they generally hold, especially as longevity increases. Here we plan a series of experiments to test predictions of these hypotheses. Because of our interest in age-specific mortality and in extreme longevity, all will ultimately analyze populations of 100,000 or more nematodes in several ways. We intend also to build upon extremely exciting results that allow us to predict (on the second day of adult life) those worms destined to live longest in a population of genetically identical individuals. We actually have developed the capability of physically separating out a sub-cohort of long-lived individuals (all worms in the populations are genetically identical), using the COPAS """"""""worm sorter"""""""", into a distinct population for subsequent analyses. These studies will reveal the dynamics of hidden heterogeneity of frailty. We will closely examine """"""""late-life"""""""" reproductive capabilities in C. elegans with a goal of ascertaining whether """"""""older"""""""" worms can reproduce under certain conditions or in certain genetic mutants. This capability also will allow direct assessment of possible artifacts resulting from the effects of induced sterility on subsequent mortality, observed in numerous studies of longevity mutants in C. elegans. We will ascertain the shape of the mortality curves throughout life, focusing on extreme longevity. We will analyze new longevity mutations and combinations of mutations that can quadruple life expectancy and maximum life span. We will study the effect of environmental determinants of extended longevity, such as caloric restriction, hormesis, and drug supplementation in large cohorts of the nematode. We will develop physiological and molecular predictors of extreme longevity.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG008761-16
Application #
7091359
Study Section
Special Emphasis Panel (ZAG1)
Project Start
Project End
Budget Start
2005-05-01
Budget End
2006-04-30
Support Year
16
Fiscal Year
2005
Total Cost
$320,405
Indirect Cost
Name
Duke University
Department
Type
DUNS #
044387793
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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