The prevalence of Type II diabetes is rapidly increasing in the US. This is in part due to the huge increase in the number of obese people. A second factor that predisposes individuals to Type II diabetes is age. As individuals age, they become more likely to develop Type II diabetes. Although the connection between obesity, aging, and the onset of Type II diabetes is clear, the molecular details remain to be determined. The long-term goal of this project is to uncover the molecular mechanism that explains the connection between insulin-like signaling, aging and fat storage, so that Type II diabetes and can be better controlled in humans. Here, we use the nematode, C. elegans, as our model system since the insulin signaling pathway is highly conserved between humans and C. elegans, and nematodes have emerged as an excellent system to study insulin signaling. In this proposal, we seek to identify new genes and new pathways coupled to the C. elegans insulin-like signaling pathway to determine how this signaling network controls both life span and fat storage. The proposed studies will test our hypothesis that mutations in the insulin-like signaling pathway lead to changes in life span and fat storage because these processes have an underlying molecular connection.
Our specific aims are to: (1) Identify the role of neurotransmitter signaling upstream of daf-2; (2) Define the role of the tub-1 gene in regulation of life span and fat storage; and (3) Determine the mechanism for JNK control of life span and fat storage. Although each aim is independent, investigating a different part of the insulin-like signaling pathway, at each step we will be analyzing the effects of mutations on life span and fat storage. We are confident that understanding the molecular connection between life span, fat storage, and insulin-like signaling will have relevance to mammalian systems because all of the genes and pathways appear conserved.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
1R01AG025891-01
Application #
6903328
Study Section
Special Emphasis Panel (ZRG1-CMAD (01))
Program Officer
Finkelstein, David B
Project Start
2005-05-01
Project End
2010-04-30
Budget Start
2005-05-01
Budget End
2006-04-30
Support Year
1
Fiscal Year
2005
Total Cost
$324,000
Indirect Cost
Name
University of Massachusetts Medical School Worcester
Department
Other Basic Sciences
Type
Schools of Medicine
DUNS #
603847393
City
Worcester
State
MA
Country
United States
Zip Code
01655
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Narasimhan, Sri Devi; Yen, Kelvin; Bansal, Ankita et al. (2011) PDP-1 links the TGF-? and IIS pathways to regulate longevity, development, and metabolism. PLoS Genet 7:e1001377
Yen, Kelvin; Narasimhan, Sri Devi; Tissenbaum, Heidi A (2011) DAF-16/Forkhead box O transcription factor: many paths to a single Fork(head) in the road. Antioxid Redox Signal 14:623-34
Yen, Kelvin; Le, Thuc T; Bansal, Ankita et al. (2010) A comparative study of fat storage quantitation in nematode Caenorhabditis elegans using label and label-free methods. PLoS One 5:

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