Our central hypothesis is that animals with reduced IGF-1 show an enhanced longevity due, at least in part, to enhanced stress resistance and a metabolic shift leading to enhanced glucose utilization. We have identified a transgenic model with a specific reduction in IGF-1 and a dwarf phenotype similar to that seen in long-lived, growth hormone deficient dwarf mice. We will use these animals to examine the influence of 1GF-I on longevity and to begin to dissect the IGF-1 dependent phenotype relative to longevity. End of life pathology will be performed on these mice to determine causes of death and to evaluate the occurrence and severity of age-related histological changes. A detailed evaluation of survival and pathology in these animals is critical for comparison to the already established mouse models with enhanced longevity, the majority of which also display reduced IGF-1 levels. Our preliminary results indicate that the IGF-1 deficient mice display an extended lifespan relative to controls. The ability to compare and contrast different aspects of the phenotype of the Igfl hypomorphs with the Snell, Ames and lit/lit mouse models will give important insight into those aspects of the phenotype that are important to longevity. Preliminary data indicates that IGF-1 signaling regulates a major mediator of stress resistance, HspVO. This potentially important link between IGF-1 and stress resistance, two important modulators of longevity, will be examined in detail. Additional data indicates that the Igfl hypomorphs have lower fasting levels of glucose. Thus, whole body metabolism will be examined in these animals to determine the effect of lower IGF-1 levels on metabolism in general, and glucose metabolism in particular. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
1R01AG022443-01A3
Application #
6975030
Study Section
Special Emphasis Panel (ZRG1-CMAD (01))
Program Officer
Finkelstein, David B
Project Start
2005-09-30
Project End
2005-10-15
Budget Start
2005-09-30
Budget End
2005-10-15
Support Year
1
Fiscal Year
2005
Total Cost
$284,436
Indirect Cost
Name
Lankenau Institute for Medical Research
Department
Type
DUNS #
125797084
City
Wynnewood
State
PA
Country
United States
Zip Code
19096
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