The goal of this proposal is to determine the molecular genetic, biochemical and physiological changes associated with two related life-extending interventions, caloric restriction and the long-lived Indy mutation. Caloric restriction (CR) is the most successful way to increase life span and delay the onset of age-related symptoms in animals. CR slows down the physiological decline and occurrence of age-related pathologies in a number of different experimental organisms. Mutations in the Indy gene in the fruit fly, Drosophila melanogaster, dramatically extend life span without a decrease in metabolic rate, physical activity or fertility. INDY is a dicarboxylate transporter of Krebs cycle intermediates and is primarily found in the plasma membrane of midgut, fat body, and oneocytes, tissues important for intermediary metabolism in the fly. The life extending effect of reducing Indy activity has been proposed to result from changes similar to those associated with CR. We will test whether Indy long-lived mutations have induced a state of CR by comparing the mortality rate, metabolic profile (e.g. lipids, glucose, glycogen, etc.) and genomic transcriptional responses of Indy long-lived flies and calorically restricted flies. In the course of these studies we will focus on determining the physiological and molecular responses to caloric restriction that lead to life span extension in the fly in order to achieve our long-term goal of understanding the molecular genetic mechanisms underlying the process of aging.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
1R01AG023088-01
Application #
6717456
Study Section
Geriatrics and Rehabilitation Medicine (GRM)
Program Officer
Finkelstein, David B
Project Start
2004-02-15
Project End
2009-01-31
Budget Start
2004-02-15
Budget End
2005-01-31
Support Year
1
Fiscal Year
2004
Total Cost
$347,650
Indirect Cost
Name
University of Connecticut
Department
Genetics
Type
Schools of Medicine
DUNS #
022254226
City
Farmington
State
CT
Country
United States
Zip Code
06030
Rogina, Blanka (2017) INDY-A New Link to Metabolic Regulation in Animals and Humans. Front Genet 8:66
Woods, Jared K; Ziafazeli, Tahereh; Rogina, Blanka (2016) Rpd3 interacts with insulin signaling in Drosophila longevity extension. Aging (Albany NY) 8:3028-3044
Woods, Jared K; Rogina, Blanka (2016) The effects of Rpd3 on fly metabolism, health, and longevity. Exp Gerontol 86:124-128
Frankel, Stewart; Woods, Jared; Ziafazeli, Tahereh et al. (2015) RPD3 histone deacetylase and nutrition have distinct but interacting effects on Drosophila longevity. Aging (Albany NY) 7:1112-29
Rogers, Ryan P; Rogina, Blanka (2014) Increased mitochondrial biogenesis preserves intestinal stem cell homeostasis and contributes to longevity in Indy mutant flies. Aging (Albany NY) 6:335-50
Woods, Jared K; Kowalski, Suzanne; Rogina, Blanka (2014) Determination of the spontaneous locomotor activity in Drosophila melanogaster. J Vis Exp :
Rogina, Blanka; Helfand, Stephen L (2013) Indy mutations and Drosophila longevity. Front Genet 4:47
Garber, Graham; Smith, Lee Ann; Reenan, Robert A et al. (2012) Effect of sodium channel abundance on Drosophila development, reproductive capacity and aging. Fly (Austin) 6:57-67
Rogers, Ryan P; Rogina, Blanka (2012) A gutsy way to extend longevity. Front Genet 3:108
Anisimov, Vladimir N; Bartke, Andrzej; Barzilai, Nir et al. (2012) The second international conference ""genetics of aging and longevity"". Aging (Albany NY) 4:305-17

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