Comparative effects of dehydroepiandrosterone sulfate on ventricular diastolic function with young and aged female mice

The adrenal steroid hormone dehydroepiandrosterone ( DHEA) and its sulfated derivative [ DHEA( S)] have been extensively studied for their potential anti-aging effects. Associated with aging, DHEA levels decline in humans, whereas other adrenal hormones remain unchanged, suggesting that DHEA may be important in the aging process. However, the effect of DHEA( S) supplementation on cardiac function in the aged has not been investigated. Therefore, we administered to young and old female mice a 60-day treatment with exogenous DHEA( S) at a dose of 0.1 mg/ml in the drinking water and compared the effects on left ventricular diastolic function and the myocardial extracellular matrix composition. The left ventricular stiffness (beta) was 0.30 +/- 0.06 mmHg/mu l in the older control mice compared with 0.17 +/- 0.02 mmHg/mu l in young control mice. Treatment with DHEA( S) decreased left ventricular stiffness to 0.12 +/- 0.03 mmHg/mu l in the older mice and increased left ventricular stiffness to 0.27 +/- 0.04 mmHg/mu l in young mice. The mechanism for the DHEA( S)-induced changes in diastolic function appeared to be associated with altered matrix metalloproteinase activity and the percentage of collagen cross-linking. We conclude that exogenous DHEA( S) supplementation is capable of reversing the left ventricular stiffness and fibrosis that accompanies aging, with a paradoxical increased ventricular stiffness in young mice.