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.
| Brenner, D A; Apstein, C S; Saupe, K W (2001) Exercise training attenuates age-associated diastolic dysfunction in rats. Circulation 104:221-6 |
