The long-term goal of our studies is to understand the molecular and genetic elements that underlie the process of aging and determine longevity. One of the most prominent hypotheses explaining the aging process is the oxidative stress hypothesis, which states that the rate of aging and life span is directly related to the accumulation of oxidative damage to organelles and macromolecules. Comparative studies between species having different life spans have been one of the foundations of the oxidative stress hypothesis, predicting a direct relationship between the accumulation of oxidative damage, the rate of aging and life span. We propose to use the fruit fly model system, Drosophila melanogaster, to compare the relationship between life span and the accrual of oxidative damage within a single, genetically well defined species, using a variety of strains and environmental and genetic conditions known to alter life span. These studies will better define the precise relationship between oxidative damage and life span, laying the foundation for a map detailing the specific quantitative relationship between oxidative damage, aging and life span. An additional advantage of using Drosophila to perform these comparative studies is that the powerful molecular and genetic techniques available in Drosophila can be used to directly identify and test specific physiological systems important in aging.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG025277-05
Application #
7640938
Study Section
Special Emphasis Panel (ZRG1-BDA-F (02))
Program Officer
Velazquez, Jose M
Project Start
2005-09-30
Project End
2011-06-30
Budget Start
2009-08-15
Budget End
2011-06-30
Support Year
5
Fiscal Year
2009
Total Cost
$291,168
Indirect Cost
Name
Brown University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
001785542
City
Providence
State
RI
Country
United States
Zip Code
02912
von Loeffelholz, Christian; Lieske, Stefanie; Neuschäfer-Rube, Frank et al. (2017) The human longevity gene homolog INDY and interleukin-6 interact in hepatic lipid metabolism. Hepatology 66:616-630
Ding, Feifei; Gil, M Pilar; Franklin, Michael et al. (2014) Transcriptional response to dietary restriction in Drosophila melanogaster. J Insect Physiol 69:101-6
Zhu, Chen-Tseh; Chang, Chengyi; Reenan, Robert A et al. (2014) Indy gene variation in natural populations confers fitness advantage and life span extension through transposon insertion. Aging (Albany NY) 6:58-69
Whitaker, Rachel; Gil, M Pilar; Ding, Feifei et al. (2014) Dietary switch reveals fast coordinated gene expression changes in Drosophila melanogaster. Aging (Albany NY) 6:355-68
Whitaker, Rachel; Faulkner, Shakeela; Miyokawa, Reika et al. (2013) Increased expression of Drosophila Sir2 extends life span in a dose-dependent manner. Aging (Albany NY) 5:682-91
Savva, Yiannis A; Jepson, James E C; Chang, Yao-Jen et al. (2013) RNA editing regulates transposon-mediated heterochromatic gene silencing. Nat Commun 4:2745
Rogina, Blanka; Helfand, Stephen L (2013) Indy mutations and Drosophila longevity. Front Genet 4:47
Jiang, Nan; Du, Guyu; Tobias, Ethan et al. (2013) Dietary and genetic effects on age-related loss of gene silencing reveal epigenetic plasticity of chromatin repression during aging. Aging (Albany NY) 5:813-24
Chamseddin, Khalil H; Khan, Sabina Q; Nguyen, Mai L H et al. (2012) takeout-dependent longevity is associated with altered Juvenile Hormone signaling. Mech Ageing Dev 133:637-46
Antosh, Michael; Fox, David; Helfand, Stephen L et al. (2011) New comparative genomics approach reveals a conserved health span signature across species. Aging (Albany NY) 3:576-83

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