Abstract 13673: Aging Impairs Cardiac Akt Activity Leading to Myocardial Sarcopenia

Introduction: Aging causes skeletal muscle atrophy (i.e. sarcopenia). In heart, aging is also known to cause cardiac dysfunction such as diastolic dysfunction; however, the impact of aging on myocardial cell growth remains uncertain. Hypothesis: Because of the pivotal role of protein kinase Akt in cellular aging and growth of cardiomyocytes, we hypothesized whether #1 aging may impairs cardiac Akt activation leading to myocardial atrophy in aged heart and #2 regular exercise may enhance cardiac Akt activity, leading to augmentation of cardiomyocyte growth that results in reversal of the aging-mediated cardiac atrophy. Methods: [cohort-1]: Male genetically senescence-accelerated [(SAM; senescence-accelerated prone (P10)] and senescence-resistant counterpart (R1) were allocated to EX [60-min running by treadmill/day for 6 months] and EX-free control (CON). [cohort-2] Male aged (40 w/o) and young (14 w/o) C57BL6 mice were subjected to the EX (agedC57EX and agedC57CON). Results: At baseline, cardiac geometry of R1 revealed normal, whereas P10 exhibited LV wall thinning and diastolic dysfunction. Systolic function of both P10 and R1 was preserved. After EX, body and heart weight (HW/BW) of R1 were increased (BW; +6.7% and HW; +3.5% versus R1CON); however, EX had no influence on HW/BW of P10. EX promoted LV hypertrophy in R1EX with concomitant increase in cardiac capillary density through activation of Akt/eNOS pathway, which was absent in P10EX. EX had no influence on systolic function of R1EX, however, EX promoted systolic dysfunction in P10EX [EF(%) 68.9±1.5 for P10EX versus 74.3±1.2 for P10CON] with attenuation of phosphorylated Akt and phospholamban levels in myocardium. In youngC57EX, EX promoted myocardial hypertrophy with augmentation of cardiac Akt/mTOR/S6K axis, which was diminished in agedC57EX. Age- and gender-matched Akt knockout mice exhibited lack of the EX-induced cardiac hypertrophy. Conclusions: Aging promotes cardiac sarcopenia in mice, in which Akt plays an essential role. EX-induced adaptive cardiac hypertrophy requires Akt activation and aging heart lacks the EX-induced Akt activation.