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

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.

CircERCC2 ameliorated intervertebral disc degeneration by regulating mitophagy and apoptosis through miR-182-5p/SIRT1 axis

“…Therefore, in this study TBHP was used to induce oxidative stress in NPCs, and AF was disrupted to induce IVDD in needle-punctured rat model. Mitophagy is a selective autophagy process that regulates cellular metabolism by specifically degrading damaged or redundant mitochondria in the cells [41][42][43] . Mitophagy has been associated with the progression of several diseases [44][45][46][47] .…”

Role of Resveratrol in Transmitochondrial AMD RPE Cells

“…Since the AMD cell lines have damaged AMD mitochondria, we speculate resveratrol exerts its protective effects by improving mitochondrial health and function. This assumption is supported by recent studies that demonstrated that resveratrol exerts its anti-aging effects in zebrafish retina by enhancing mitochondrial quality and growth, suppressing Akt/mTOR pathway, and upregulating Ampk/Sirt1/PGC-1α [30]. Furthermore, systemic treatment in AMD patients that may have modulated the mitochondrial DNA status of patients could certainly influence the AMD cybrid cells' response to resveratrol.…”

Zanthoxylum nitidum extract attenuates BMP-2-induced inflammation and hyperpermeability

“…RNA was extracted and analyzed using the previous method [ 25 ]. Total RNA was obtained by the Trizol reagent (Invitrogen, Carlsbad, CA) and quantified by Nanodrop.…”