Abstract 178: Exercise Augments Cardiac Akt Activity And Reverses Aging-related Systolic Dysfunction.

Abstract

Purpose: Aging is one of the primary factors causing left-ventricular (LV) remodeling and susceptibility to heart failure (HF). Clinical evidences demonstrate a sustained exercise (EX) ameliorates HF; however, the molecular mechanism underlying the aging-related LV remodeling remains uncertain and few data have demonstrated whether EX may be beneficial for the aging-related LV remodeling and contractility. Because preclinical studies indicate the pivotal role of protein kinase Akt in aging, we thus hypothesized whether EX may exert benefits on HF induced by aging in which Akt may play an essential role. Methods: Male aged (40 w/o) and young (14 w/o) C57BL6 mice were subjected to the EX (45-min running (10~20m/s, 5-degree) on treadmill every second day for 15 weeks; agedC57EX and agedC57CON). To elucidate the role of Akt in aging heart, age- and gender-matched Akt knockout mice were also enrolled. Results: Aging impairs both systolic and diastolic function without any changes in cardiac geometry. The systolic dysfunction of agedC57 reversed by EX with concomitant Akt activation; however, its diastolic dysfunction remained unaffected. EX enhanced cardiac Akt activity independently of aging. Aged AktKO exhibited systolic dysfunction to the more severe extent, which was reversed by EX. Conclusions: Our study demonstrates that #1 Akt is essential for adaptive cardiac contractility both to EX and aging. #2 Aging promotes diastolic dysfunction independently of Akt axis.