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.

The Study on the Antioxidative Activity of Resveratrol in Senescence-Accelerated Mouse Prone/8 (SAMP8)

In the present study, we examined resveratrol(RES)extracted from Polygonum cuspidatum on antioxidative effects in the senescence-accelerated mouse (SAM). We fed resveratrol to young adult SAM mice at doses of 25,50,100mg/(kg•bw) in their standard powder diet for 8-week. The body weight, organ weights and oxidation products of malondialdehyde (MDA) in the liver of the SAM were determined. The results showed that the SAM mice were no dose-related change in either body weight or organ weights, the amount of MDA declined distinctly in the mouse liver. In conclusion, resveratrol may have an antioxidant effect.

Rose (Rosa rugosa)-flower extract increases the activities of antioxidant enzymes and their gene expression and reduces lipid peroxidation

The effects of rose-flower extract on antioxidant enzymes were studied. The activities of catalase (CAT) and glutathione peroxidase (GPx) in 9-month-old senescence-accelerated mice (SAM mice) were lower than those in 6-month-old SAM mice. Therefore, 9-month-old SAM mice were the most appropriate targets for treatment with the rose-flower extract. The activities of CAT and GPx in SAM mice treated with rose-flower extract showed a marked increase in whole blood and liver. At the same time, the gene-expression level of CAT and GPx was upregulated in the liver, while malondialdehyde content in liver and brain decreased. Male SAM mice were more sensitive than female SAM mice. The mean and the longest lifespan of SAM mice were longer after treatment with rose-flower extract.Key word: anti-aging, CAT, GPx, lipid peroxidation.