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Exercise renovates H2S and Nrf2-related antioxidant pathways to suppress apoptosis in the natural ageing process of male rat cortex


Ageing is a complex biological process that increases the probability of disease and death, which affects the organs of all species. The accumulation of oxidative damage in the brain contributes to a progressive loss of cognitive functions or even declined the energy metabolism. In this study, we tested the effects of exercise training on the apoptosis, survival, and antioxidant signaling pathways in the cerebral cortex of three age groups of male rats; 3, 12, and 18 months. We observed that H2S and the expression of Nrf2-related antioxidant pathways declined with age and increased after exercise training. IGF1R survival pathway was less increased in middle-aged rats; however, significantly increased after exercise training. The expression of mitochondrial-dependent apoptotic pathway components, such as Bak, cytochrome C, and caspase 3 in the ageing control group, were much higher than those of the exercise training groups. This study demonstrated that exercise training could reduce the apoptosis and oxidative stress that accrues throughout ageing, which causes brain damage.

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Data availability

The raw data used and/or analyzed during the current study are available from the corresponding author on reasonable request.



Cystathionine β-synthase




Hydrogen sulfide


Nuclear factor E2-related factor 2


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We thank that this work is supported grants from Hualien Tzu Chi Hospital (Buddhist Tzu Chi Medical Foundation), China Medical University, Asia University, and China Medical University Hospital in Taiwan (IMAR-110-01-16, CMU107-ASIA-01, and DMR-105-011).

Author information




JL, TH, and CH supervised the study. BCT and CC wrote the manuscript. BCT and CC performed the histological examination of the tissue, and data analysis. WK, HK, TH, RC, and CH analyzed the data and had contributions to the conception. VPV and CH had contributions to interpretation of data and substantively revised it. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Chih-Yang Huang.

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The authors declare that there are no conflicts of interest.

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All protocols were approved by the Institutional Animal Care and Use Committee of Central Taiwan University of Science and Technology, Taichung, Taiwan.

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Lin, JY., Ho, TJ., Tsai, B.CK. et al. Exercise renovates H2S and Nrf2-related antioxidant pathways to suppress apoptosis in the natural ageing process of male rat cortex. Biogerontology 22, 495–506 (2021).

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  • Age-related
  • Brain
  • H2S
  • Apoptosis
  • Anti-oxidant