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Research Paper|Volume 11, Issue 10|pp 3117—3137

Exploration of age-related mitochondrial dysfunction and the anti-aging effects of resveratrol in zebrafish retina

Ning Wang1,2, Zhiwen Luo1,2, Ming Jin1, Weiwei Sheng1,2, Han-Tsing Wang3,4,5, Xinyi Long1,2, Yue Wu1,2, Piaopiao Hu1,5, Hong Xu3,4,5, Xu Zhang1,5
  • 1Affiliated Eye Hospital of Nanchang University, Jiangxi Research Institute of Ophthalmology and Visual Science, Nanchang, China
  • 2Queen Mary School of Nanchang University, Nanchang, China
  • 3Institute of Life Science of Nanchang University, Nanchang, China
  • 4School of Life Sciences of Nanchang University, Nanchang, China
  • 5Jiangxi Provincial Collaborative Innovation Center for Cardiovascular, Digestive and Neuropsychiatric Diseases, Nanchang, China

* * Equal contribution

Received: February 1, 2019Accepted: May 7, 2019Published: May 19, 2019
https://doi.org/10.18632/aging.101966

Copyright: Wang et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

It is currently believed that aging is closely linked with mitochondrial dysfunction, and that resveratrol exhibits anti-aging and neuroprotective effects by improving mitochondrial function, even though the mechanisms are not well defined. This study explored mitochondrial quality (mitochondrial DNA integrity and copy number), mitochondrial function (fusion/fission, mitophagy/autophagy), antioxidant system and activity of the Akt/mTOR and Ampk/Sirt1/Pgc1α pathways, and inflammation in aging zebrafish retinas to identify the probable mechanisms of resveratrol’s anti-aging and neuroprotective effects. mtDNA integrity, mtDNA copy number, mitochondrial fusion regulators, mitophagy, and antioxidant-related genes were all decreased whereas Akt/mTOR activity and inflammation was increased upon aging in zebrafish retinas. Resveratrol was shown to not only increase mitochondrial quality and function, but also to suppress Akt/mTOR activity in zebrafish retinas. These results support the notion that mitochondrial dysfunction and increased Akt/mTOR activity are major players in age-related retinal neuropathy in zebrafish, and demonstrate a trend towards mitochondrial fragmentation in the aging retina. Importantly, resveratrol promoted mitochondrial function, up-regulating Ampk/Sirt1/Pgc1α, and down-regulated Akt/mTOR pathway activity in zebrafish retinas, suggesting that it may be able to prevent age-related oculopathy.