Aging is associated with loss of skeletal muscle quality, quantity, and strength (sarcopenia). TNFa is expressed in skeletal muscle and is known to be involved in insulin resistance and LPL regulation. Low LPL activity is associated with the high triglyceride-low HDL cholesterol dyslipidemia, which is predictive of coronary heart disease. Preliminary data from this research group suggested that old subjects had higher TNFa and lower LPL. The research group also had preliminary evidence that strength training decreases TNFa and increases LPL in muscle. The hypotheses of the proposal are that 1) The process of aging coordinately increases TNFa and decreases LPL expression in skeletal muscle; and that 2) resistance exercise training coordinately decreases TNFa and increases LPL expression in skeletal muscle.
The first aim i s to test the effect of aging on muscle TNFa and LPL by using a cross-sectional comparison of men and women from 4 different age groups: young (20-30y), middle-aged (40-50y), young-old (60-70y), and old-old (>78y). Since the effects of TNFa are suspected to be mediated by insulin resistance or impaired insulin receptor signal, insulin sensitivity will be measured using the hyperinsulinemic-euglycemic clamp method.
The second aim i s to evaluate the effects of resistance exercise training on TNFa, and LPL in skeletal muscle with 3 month strength training intervention. Four muscle biopsies will be performed at different time points of the treatment period. It is believed that these results will provide insight into the role of exercise in reversing age-related metabolic deterioration of skeletal muscle.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG014658-03
Application #
6341517
Study Section
Geriatrics and Rehabilitation Medicine (GRM)
Program Officer
Dutta, Chhanda
Project Start
1999-01-01
Project End
2003-12-31
Budget Start
2001-01-15
Budget End
2001-12-31
Support Year
3
Fiscal Year
2001
Total Cost
$245,925
Indirect Cost
Name
Washington University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
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