PUBLICATION

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

Authors
Wang, N., Luo, Z., Jin, M., Sheng, W., Wang, H.T., Long, X., Wu, Y., Hu, P., Xu, H., Zhang, X.
ID
ZDB-PUB-190521-2
Date
2019
Source
Aging   11(10): 3117-3137 (Journal)
Registered Authors
Xu, Hong
Keywords
aging zebrafish, mTOR, mitochondrial dysfunction, mitophagy, resveratrol, retina
MeSH Terms
  • Aging/drug effects*
  • Aging/metabolism
  • Animals
  • Antioxidants/metabolism
  • Antioxidants/therapeutic use*
  • DNA, Mitochondrial/metabolism*
  • Drug Evaluation, Preclinical
  • Mitochondrial Dynamics
  • Mitophagy/drug effects
  • Resveratrol/therapeutic use*
  • Retinal Diseases/drug therapy
  • Retinal Diseases/metabolism*
  • Zebrafish
PubMed
31105084 Full text @ Aging (Albany NY)
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.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping