Resveratrol and SIRT1: Antiaging Cornerstones for Oocytes?

Abstract

It is well-known that there is an enormous variability in the aging-related decline of oocytes’ quantity and their developmental competence among mammalian species. The implication of female germline aging is profound from the perspective of evolutionary conservation of the aging mechanism, a topic of continuous and widespread interest that has yet to be fully addressed for the mammalian oocyte. There is a certain need to develop novel antiaging strategies to delay or slow down aging, or even to reverse the aging phenotype in the oocyte. In the past two decades, several antioxidants have been tested for this purpose. Resveratrol is one of these latter-mentioned compounds, which has shown anti-inflammatory and antiaging properties in a dose-dependent manner. Interestingly, resveratrol appears to enhance the activity of so-called Sirtuin 1, too. Therefore, the aim of this review is to summarize and discuss the latest findings related to resveratrol, Sirtuin 1, and their crosstalk and influence on the mammalian oocyte to elucidate the question of whether these factors can delay or slow down reproductive aging.

Effect of Resveratrol on Markers of Oxidative Stress and Sirtuin 1 in Elderly Adults with Type 2 Diabetes

“…We also observed a statistically significant increase in SIRT1 concentrations in the EG1000, which is consistent with the proposed mechanism of RV [ 63 , 64 ]. In this sense, SIRT1 has an effect on the regulation of autophagy, mitophagy, mitochondrial biogenesis, the expression of antioxidant enzymes and the suppression of NFκB, among others [ 63 ].…”

“…In this sense, SIRT1 has an effect on the regulation of autophagy, mitophagy, mitochondrial biogenesis, the expression of antioxidant enzymes and the suppression of NFκB, among others [ 63 ]. Likewise, the production, expression and activity of SIRT1 can be modified by RV in an allosteric way [ 64 ] so that an increase in SIRT1 levels provides indirect information on the effects of RV [ 63 ]. On the other hand, when SIRT1 is stimulated, it deacetylates and activates the LKB1 protein kinase, which phosphorylates and activates AMPK, thereby attenuating oxidative damage, improving insulin resistance and restoring energy homeostasis [ 64 ].…”

“…Likewise, the production, expression and activity of SIRT1 can be modified by RV in an allosteric way [ 64 ] so that an increase in SIRT1 levels provides indirect information on the effects of RV [ 63 ]. On the other hand, when SIRT1 is stimulated, it deacetylates and activates the LKB1 protein kinase, which phosphorylates and activates AMPK, thereby attenuating oxidative damage, improving insulin resistance and restoring energy homeostasis [ 64 ]. Regarding the role of SIRT1 in energy metabolism, scientific evidence suggests that it increases oxidative phosphorylation through the deacetylation of PGC-1α and thereby functions as a regulator of mitochondrial biogenesis in the liver and muscle [ 65 ]; PGC-1α controls the expression of genes that regulate biogenesis and mitochondrial activity, decreasing lipid accumulation and increasing glucose uptake, thereby improving energy metabolism [ 66 ].…”

Ovarian aging: energy metabolism of oocytes

“…SIRT1 regulates mitochondrial activity and is one of the protective factors against ovarian oxidative stress and glucose stress [162,173,[183][184][185]. Enhancing SIRT1 can protect oocyte quality and delay reproductive aging [186]. Inhibiting SIRT1 impairs mitochondrial function and OXPHOS [187].…”

Editorial: Stem cell exhaustion in aging

“…Intriguingly, a downstream effector of caloric restriction is NAD + pool and sirtuins (SIRT) gene family. In particular, SIRT1 activation was suggested to be the mechanism behind Resveratrol-mediated prevention of oocyte aging (Grzeczka and Kordowitzki, 2022). While all these findings suggest intriguing clinical interventions, the path towards saving oocytes from aging seems to not be straightforward.…”