In this proposal We hypothesize that derangement's in carbohydrate metabolism of aging is associated with parallel changes in body composition. We plan to demonstrate these changes during the life span of rats, focusing mainly on muscle and hepatic glucose metabolism and intracellular pathways. We also hypothesize that caloric restriction may reverse many of the derangement's in glucose metabolism of aging rats.
Our Specific Aims are to study in aging rats: 1) The effects of body composition and plasma FFA concentration on insulin- and glucose-mediated glucose disposal, glycolysis, and glycogen synthesis. 2) The effects of body composition and plasma FFA concentration on in vivo hepatic glucose fluxes, glycogenolysis, gluconeogenesis. 3) The correlation between the specific alterations in in vivo hepatic and skeletal muscle glucose fluxes and the in vitro kinetics of the rate-determining enzymes of these metabolic pathways, such as glycogen synthase, glucokinase and glucose-6-phosphatase. 4) The impact of early intervention by caloric restriction on body composition and peripheral and hepatic glucose fluxes. Studies will be conducted in 2 rat models: Fischer 344 and Sprauge-Dawley, in 4 different age groups. The significance of this proposal is two fold. First it will quantify the role of increased fat mass on glucose metabolism in aging. Second, if not all impairment is fat mass related, it may point to the mechanisms that are true senescence.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08AG000639-02
Application #
2048466
Study Section
Biological and Clinical Aging Review Committee (BCA)
Project Start
1994-09-01
Project End
1999-08-31
Budget Start
1995-09-01
Budget End
1996-08-31
Support Year
2
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Albert Einstein College of Medicine
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
009095365
City
Bronx
State
NY
Country
United States
Zip Code
10461
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Barzilai, N; Gupta, G (1999) Revisiting the role of fat mass in the life extension induced by caloric restriction. J Gerontol A Biol Sci Med Sci 54:B89-96;discussion B97-8
Barzilai, N; Gupta, G (1999) Interaction between aging and syndrome X: new insights on the pathophysiology of fat distribution. Ann N Y Acad Sci 892:58-72
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Massillon, D; Barzilai, N; Hawkins, M et al. (1997) Induction of hepatic glucose-6-phosphatase gene expression by lipid infusion. Diabetes 46:153-7

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