Abstract 443: Long-Term Testosterone Deficiency Modifies Frailty and Cardiac Structure and Function in Aging Male Mice

Abstract

Objective: Low circulating testosterone levels are correlated with heart diseases in older adults. The belief that low testosterone contributes to poor health and promotes frailty has dramatically increased testosterone prescriptions in recent years. Still links between low testosterone, frailty and the heart are unclear in part because preclinical studies typically use young, healthy animals. Here we investigated effects of chronic testosterone deficiency on frailty, body composition and cardiac structure/function in aging mice. Methods: Male C57BL/6 mice (18-21 mos) underwent a gonadectomy (GDX) or sham surgery (4-wks of age) and then were aged naturally. Sham (n=10-13) and GDX mice (n=11) were tested for frailty (frailty index (FI) tool), echocardiography, electrocardiography (ECG), blood pressure, and serum testosterone (ELISA, facial vein). Body composition was measured with dual-energy X-ray absorptiometry. Mice were anaesthetized (isoflurane) during all procedures except FI scoring. Results: Serum testosterone levels were lower in GDX mice than in sham controls (0.89±0.13 vs. 0.29±0.06 ng/mL; p<0.05). Systolic and diastolic blood pressures were unchanged between groups. Interestingly, GDX mice had lower lean mass than sham mice (23.5±1.2 vs. 27.4±0.7 g; p<0.05) but they were actually less frail (FI scores=0.17±0.05 vs. 0.23±0.01; p<0.05). GDX also reduced heart mass (186±11 vs. 148±15 mg; p<0.05) and prolonged the QRS complex (8.5±0.3 vs. 10.0±0.4 ms; p<0.05) without altering heart rate. While end systolic volume was reduced by GDX (p<0.05), ejection fraction, fractional shortening, and cardiac output remained unchanged. Conclusions: Chronic exposure to low circulating testosterone prolonged ventricular conduction time, reduced heart mass and lowered lean mass in aging male mice. This suggests that testosterone deficiency may promote electrical and contractile dysfunction in the setting of aging. However, despite adverse effects on the heart and lean muscle mass, frailty scores were actually lower in mice with chronic testosterone deficiency. This suggests that the impact of low testosterone on overall health is complex and raises questions about the benefits of testosterone supplementation in frail older adults.