Chronic moderate‑intensity exercise can induce physiological hypertrophy in aged cardiomyocytes through autophagy, with minimal Yap/Taz involvement

Figures

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  Figure 1. Representative histological features used in assessing microstructure changes in each group. (A) Normal cardiomyocyte diameter with no myofiber disarray. (B) Cardiomyocyte hypertrophy with disarrayed heart muscle. (C) Cardiomyocyte hypertrophy, disarrayed heart muscle and focal fibrosis. Images captured with Olympus CX21 and Optilab advance plus in x400 magnification. MD, muscle disarray; FF, focal fibrosis; yellow line, cardiomyocyte diameter; red arrow, erythrocytes.

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  Figure 2. Relative Gene Expression of Myh6, Myh7 and Myh6/Myh7 ratio in control and intervention groups. (A) The bar graph denotes the relative gene expression levels of Myh6 and Myh7, and (B) the Myh6/Myh7 ratio measured using conventional PCR. Grey bars are the control group and the white bars are the intervention group. Data are presented as the mean ± SD. Myh6 expression was significantly increased in the intervention group compared with the control (P<0.01), while Myh7 expression showed no significant difference between the two groups. However, the Myh6/Myh7 ratio was significantly higher in the intervention group (P<0.01). Statistical significance was determined using a t-test for Myh6 and Myh7 and Mann-Whitney U test for the Myh6/Myh7 ratio. **P<0.01 and ***P<0.001. ns, no significance (P>0.05).

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  Figure 3. Expression level of genes related with autophagy in the control vs. intervention groups. The bar graph demonstrated the relative expression level of autophagy-related genes (LC3, p62, mTOR and PI3K) and the Hippo pathway genes (Yap and Taz). Grey bars are the control group and the white bars are the intervention group. The data are presented as the mean ± SD. Note the expression pattern of LC3 and p62 implicated increased autophagy in the intervention group. The expression of mTOR and PI3K, both involved in regulating autophagy, is also shown, with statistically significant downregulation in the intervention group compared with the control group. Statistical significance was determined using the Mann-Whitney U Test for the p62 and Yap genes, and independent t-tests were used for the LC3, p62, mTOR and PI3K genes. *P<0.05, **P<0.01 and ***P<0.001.

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  Figure 4. Diagram demonstrating the relationship between hypertrophy and genes measured in the present study. Shown is a diagram depicting the relationship between old age and physical exercise. Old age is known to cause decreased cardiomyocytes and may be reversed with exercise. Exercise was found to induce physiological hypertrophy through activation of the AMPK pathway and inhibition of PI3K/AKT. This inhibition, in turn, inhibits mTOR function, which increases the activity of the autophagy pathway. This increased activity inhibited Yap/Taz function because these proteins are the substrate of autophagy.