Aging impairs the functioning of cardiomyocyte mitochondria in two ways that likely contribute to the increase in heart disease with aging. First, aging impairs myocardial oxidation of free fatty acids which are the main source of ATP for the heart. Second, aging increases mitochondrial production of free radicals. It is our overall hypothesis that these two age- associated changes in mitochondrial function cause much of the age-associated decline in cardiac physiology, and that reversing the impaired mitochondrial function would """"""""rejuvenate"""""""" the heart in a clinically significant way. Many age-associated changes in mitochondrial function can be reversed with dietary supplementation of carnitine derivatives such as acetyl-L- carnitine, a critical co-factor in fatty acid metabolism. To date, carnitine's ability to reverse age-associated deterioration of mitochondrial function has only been documented on a sub- cellular level. With aging, blood, skeletal muscle and heart concentrations of carnitine decreases, but can be restored with dietary supplementation.
Our Specific Aims are to test the hypotheses that dietary carnitine supplementary will improve three process that deteriorate with aging: 1) the heart's ability to consume oxygen and increase work output 2) the heart's tolerance to ischemia and reperfusion 3) maximal exercise capacity.
Specific Aims 1 and 2 will be conducted from 3 months old and 24 months old Fisher 344 rats using a unique isolated heart preparation. Studies will be conducted at Boston University School of Medicine and at Brigham and Women's Hospital. Combining the resources of these two laboratories allows us to study the effect of aging on the heart in an integrative way, from a biochemical level to the whole animal level.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Small Research Grants (R03)
Project #
1R03AG016908-01
Application #
2855879
Study Section
National Institute on Aging Initial Review Group (NIA)
Program Officer
Finkelstein, David B
Project Start
1999-04-01
Project End
2001-03-31
Budget Start
1999-04-01
Budget End
2001-03-31
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Boston University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
Brenner, D A; Apstein, C S; Saupe, K W (2001) Exercise training attenuates age-associated diastolic dysfunction in rats. Circulation 104:221-6