Abstract 204: Loss Of Akt Caused Aging-induced Cardiac Systolic Dysfunction But Is Independent From Comorbid Diastolic Dysfunction In Aging.
PURPOSE: Aging is one of the primary factors causing cardiac dysfunction. Diastolic dysfunction (DD) is primary characteristics for aging-induced heart failure. Clinical evidences demonstrate a sustained exercise (EX) ameliorates DD; however, it remains unclear whether EX may ameliorate the aging-related DD and the underlying molecular mechanism. We thus evaluated whether EX may ameliorate cardiac dysfunction in aging and the role of Akt in the EX-induced effects on aging heart.
Methods: Male senescence-accelerated (SAM) mice (P10) and its aging-resistant control (R1) were allocated to exercise [EX; 60-min running on treadmill every single day for 6 months (P10-EX and R1-EX)] and exercise-free control groups (P10-ctl and R1-ctl). Age-matched C57BL6 mice were subjected to the same EX protocol (C57-EX and C57-ctl) to compare any influence of genetic background. To elucidate the role of Akt in aging-induced changes in heart, analysis of aged Akt knockout mice (AktKO) were conducted.
Results: At baseline, cardiac geometry of R1 strain revealed normal, whereas P10 strain exhibited reduced LV wall thickness and DD. The s-LVF of both strains was preserved. After EX, the body and heart weight of R1 mice were increased (BW; +6.7% and HW; +3.5% versus R1-ctl); however, EX had no influence on BW and HW of P10. EX promoted LV hypertrophy in R1, which was absent in P10-EX. The d-LVF of R1-EX was impaired but their s-LVF was unchanged. In contrast, s-LVF of P10-EX turned impaired [EF(%) 68.9±1.5 vs 74.3±1.2 for P10-ctl], whereas the underlying DD of P10 was unaffected by EX. In C57-EX, cardiac function exhibited the similar trends observed in R1-EX. Cardiac Akt activity of R1-EX and C57-EX were enhanced compared to controls, which was diminished in P10-EX. Aged AktKO exhibited impaired s-LVF [EF(%)61.3±1.0], nonetheless their DD remained unchanged [E/A=2.5±0.3, Dct (msec)= 35.0±2.4].
Conclusions: Our study demonstrates that #1 Akt is essential for adaptive response of LV hypertrophy to EX, #2 aging impairs Akt signaling in heart, leading to systolic dysfunction, and #3 Akt is independent from modulation of cardiac DD induced by aging. Clinical implications are drawn that the benefit of EX on DD may be irrelevant to the aged population.
- © 2013 by American Heart Association, Inc.