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Resveratrol enhanced FOXO3 phosphorylation via synergetic activation of SIRT1 and PI3K/Akt signaling to improve the effects of exercise in elderly rat hearts

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Abstract

Exercise training is considered a benefit to heart function, but the benefit in aging hearts remains unknown. Activation of the PI3K-Akt survival pathway and suppression of Fas/FADD/caspase-8 apoptotic signaling by exercise training in hearts from young subjects have been described in our previous studies. However, the mechanisms are still unclear and need to be explored in aging hearts. Thus, 18-month-old rats were used as a model and underwent swimming exercise training, resveratrol treatment (15 mg/kg/day), or exercise training with resveratrol treatment for 1 month. The results showed that heart function in each group improved. However, the 18-month-old rats in the exercise-only group experienced the slightly inevitable impact of increased TNF-α, cell apoptosis, and fibrosis. In the protein analysis, the PI3K-Akt pathway was slightly increased with exercise training and resveratrol treatment, but Sirtuin 1 (SIRT1) was only highly activated with resveratrol treatment in the aged rat hearts. Moreover, the exercise training plus resveratrol group benefited from SIRT1 and PI3K-Akt dual pathways and blocked FOXO3 accumulation. Our experimental results strongly suggest that resveratrol treatment improves the beneficial effects of exercise training in aging rat hearts.

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Acknowledgments

This study is supported in part by the Taiwan Department of Health Clinical Trials and Research Center of Excellence (DOH102-TD-B-111-004), China medical university (CMU99-NTU-01), and National Science Council (NSC101-2410-H-029-055).

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Authors and Affiliations

  1. Department of Family Medicine, China Medical University Hospital, Taichung, Taiwan

    Chih-Hsueh Lin & Cheng-Chieh Lin

  2. School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan

    Chih-Hsueh Lin & Cheng-Chieh Lin

  3. Ph.D. Program for Aging, China Medical University, Taichung, Taiwan

    Chih-Hsueh Lin & Cheng-Chieh Lin

  4. Graduate Institute of Basic Medical Science, China Medical University, No 91, Hsueh-Shih Road, 404, Taichung, Taiwan

    Wei-Jen Ting & Chih-Yang Huang

  5. Division of Cardiology, China Medical University Hospital, Taichung, Taiwan

    Pei-Ying Pai

  6. Laboratory of Exercise Biochemistry, Taipei Physical Education College, Taipei, Taiwan

    Chia-Hua Kuo

  7. School of Chinese Medicine, China Medical University, Taichung, Taiwan

    Tsung-Jung Ho & Chih-Yang Huang

  8. Chinese Medicine Department, China Medical University Beigang Hospital, Beigang, Taiwan

    Tsung-Jung Ho

  9. Department of Biological Science and Technology, China Medical University, Taichung, Taiwan

    Wei-Wen Kuo

  10. Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan Town, Taiwan

    Chung-Ho Chang

  11. Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan

    Chih-Yang Huang

  12. Department of Hospitality Management, College of Agriculture, Tunghai University, No. 181, Sec. 3, Taichung Port Rd., Situn District, 40704, Taichung City, Taiwan

    Wan-Teng Lin

Authors
  1. Chih-Hsueh Lin
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  2. Cheng-Chieh Lin
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  3. Wei-Jen Ting
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  4. Pei-Ying Pai
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  5. Chia-Hua Kuo
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  6. Tsung-Jung Ho
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  7. Wei-Wen Kuo
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  8. Chung-Ho Chang
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  9. Chih-Yang Huang
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  10. Wan-Teng Lin
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Corresponding authors

Correspondence to Chih-Yang Huang or Wan-Teng Lin.

Additional information

Chih-Yang Huang and Wan-Teng Lin contributed equally.

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Lin, CH., Lin, CC., Ting, WJ. et al. Resveratrol enhanced FOXO3 phosphorylation via synergetic activation of SIRT1 and PI3K/Akt signaling to improve the effects of exercise in elderly rat hearts. AGE 36, 9705 (2014). https://doi.org/10.1007/s11357-014-9705-5

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  • DOI: https://doi.org/10.1007/s11357-014-9705-5

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