Caloric restriction (CR), a decrease in nutritional level without causing malnutrition, is well known to increase lifespan across species, from yeast to rodents. Ad libitum feeding can therefore be viewed as having a toxic effect on lifespan. Indeed, overnutrition in humans is one of the leading risk factors for age-related diseases and mortality. We propose to characterize the effects of overnutrition in Drosophila, and seek ways to mitigate them by finding mutants that show either enhanced sensitivity or resistance to overnutrition. The identification of molecular pathways involved should provide tools in the understanding of this phenomenon, by leading us to the downstream genes that manifest the lifespan changes. Examination of the pathological and physiological changes resulting from overnutrition in normal and mutant flies will cast light on their involvement in aging and age-related diseases. Most investigations have been directed at the effects of undernutrition as a beneficial factor in extending lifespan. This proposal represents an alternate approach, focusing on overnutrition to exaggerate deleterious effects, thus providing a sensitized system in which to discover methods of ameliorating them.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG024366-05
Application #
7455264
Study Section
Special Emphasis Panel (ZAG1-ZIJ-5 (M3))
Program Officer
Finkelstein, David B
Project Start
2004-09-15
Project End
2009-12-30
Budget Start
2008-07-15
Budget End
2009-12-30
Support Year
5
Fiscal Year
2008
Total Cost
$371,485
Indirect Cost
Name
California Institute of Technology
Department
Type
Schools of Arts and Sciences
DUNS #
009584210
City
Pasadena
State
CA
Country
United States
Zip Code
91125
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