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Aging-US: Mitochondrial dysfunction and the effects of resveratrol in zebrafish

09-08-2021

Aging-US published a Special Collection on Eye Disease which included "Exploration of age-related mitochondrial dysfunction and the anti-aging effects of resveratrol in zebrafish retina" which reported that 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/Pgc1, and down-regulated Akt/mTOR pathway activity in zebrafish retinas, suggesting that it may be able to prevent age-related oculopathy.

Dr. Xu Zhang from The Jiangxi Research Institute of Ophthalmology and Visual Science as well as The Jiangxi Provincial Collaborative Innovation Center for Cardiovascular said, "Aging is the biological process characterized by the accumulation of damage in structure and decline in function of cells and tissues over time, ultimately leading to organismal death."

The causes of aging are complex but include abnormal mitochondria, epigenetic alterations, increased reactive oxygen species, increased DNA methylation, and decreased telomere length. Recently, both dysfunctional mitochondria that overproduce ROS and abnormal mitochondrial dynamics have been recognized as crucial contributors to the aging process as well as age-related neuronal diseases and age-related oculopathies such as glaucoma, age-related macular degeneration, and cataracts.

Figure 12. Resveratrol treatment timeline. All treatments began at 0 hour and the time points are post-resveratrol administration. CON/aging, 0.04% ethanol; RES, 20mg/L resveratrol + 0.04% ethanol.

Fusion can help relieve mtDNA damage by diluting mutant mtDNA with non-mutant mtDNA, whereas fission can allow for turnover of mutant mtDNA through mitophagy. On the other hand, mitochondrial fragmentation is associated with apoptosis and cell death rather than mitophagy and must be distinguished from fission.

Resveratrol, a plant natural product found in high levels in peanuts and grape skin, has well-established antioxidant, anti-inflammatory, anti-mutagenic, neuroprotective, and anti-aging effects in many species. Current evidence suggests that the anti-aging effects of resveratrol are related to its ability to modulate mitochondria. Resveratrol has been found to increase mitochondrial fusion/fission as well as promote Pink1 expression and autophagic activity.

Resveratrol has been found to increase mitochondrial fusion/fission as well as promote Pink1 expression and autophagic activity.

The Zhang Research Team concluded in their Aging-US Research Output, "Maintaining mitochondrial health is crucial to prevent age-related neurodegenerative diseases, including oculopathy. We utilized the zebrafish retina as a model for age-related oculopathy and observed decreased mtDNA integrity, dysfunctional mitochondrial fission-fusion dynamics, decreased expression of antioxidant defense enzymes, and increased activity of the Akt/mTOR pathway in the aging retina. Consistent with its anti-aging effects in other species and model systems, resveratrol treatment helped alleviate most of the age-related changes observed in the zebrafish retina, suggesting its potential for the prevention of aging-induced oculopathy in other species including humans. This study indicates that further testing of resveratrol for oculopathy is warranted, and helps establish the zebrafish retina as a viable model of age-related oculopathy for further studies on the molecular mechanisms and for novel drug screening."

Full Text - https://www.aging-us.com/article/101966/text

Correspondence to: Xu Zhang email: xuzhang19@163.com

Keywords: aging zebrafish, retina, mitochondrial dysfunction, mitophagy, mTOR, resveratrol

About Aging-US:

The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population.

The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.)

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