Resveratrol shortens the chronological lifespan of Saccharomyces cerevisiae by a pro‐oxidant mechanism

Abstract

The antioxidant phenotype caused by resveratrol has been recognized as a key piece in the health benefits exerted by this phytochemical in diseases related to aging. It has recently been proposed that a mitochondrial pro‐oxidant mechanism could be the cause of resveratrol antioxidant properties. In this regard, the hypothesis that resveratrol impedes electron transport to complex III of the electron transport chain as its main target suggests that resveratrol could increase reactive oxygen species (ROS) generation through reverse electron transport or by the semiquinones formation. This idea also explains that cells respond to resveratrol oxidative damage, inducing their antioxidant systems. Moreover, resveratrol pro‐oxidant properties could accelerate the aging process, according to the free radical theory of aging, which postulates that organism's age due to the accumulation of the harmful effects of ROS in cells. Nonetheless, there is no evidence linking the chronological lifespan (CLS) shorten occasioned by resveratrol with a pro‐oxidant mechanism. Hence, this study aimed to evaluate whether resveratrol shortens the CLS of Saccharomyces cerevisiae due to a pro‐oxidant activity. Herein, we provide evidence that supplementation with 100 μM of resveratrol at 5% glucose: (1) shortened the CLS of ctt1Δ and yap1Δ strains; (2) decreased ROS levels and increased the catalase activity in WT strain; (3) maintained unaffected the ROS levels and did not change the catalase activity in ctt1Δ strain; and (4) lessened the exponential growth of ctt1Δ strain, which was restored with the adding of reduced glutathione. These results indicate that resveratrol decreases CLS by a pro‐oxidant mechanism.

Microbial Secondary Metabolites via Fermentation Approaches for Dietary Supplementation Formulations

“…For instance, E. coli has been engineered to produce various phenolics, including resveratrol [ 116 ], a well-known antioxidant compound found in grapes and red wine. It was initially believed that resveratrol was only produced by plants, but later studies revealed that certain species of bacteria and fungi can also synthesize this compound (e.g., Saccharomyces cerevisiae ) [ 117 , 118 , 119 ]. By introducing specific genes encoding enzymes involved in phenolic biosynthesis, researchers have successfully developed bacterial strains capable of producing these compounds; Yeast production: certain strains of yeast, such as Saccharomyces cerevisiae , have been engineered to produce phenolic compounds [ 117 , 118 , 119 ].…”

“…It was initially believed that resveratrol was only produced by plants, but later studies revealed that certain species of bacteria and fungi can also synthesize this compound (e.g., Saccharomyces cerevisiae ) [ 117 , 118 , 119 ]. By introducing specific genes encoding enzymes involved in phenolic biosynthesis, researchers have successfully developed bacterial strains capable of producing these compounds; Yeast production: certain strains of yeast, such as Saccharomyces cerevisiae , have been engineered to produce phenolic compounds [ 117 , 118 , 119 ]. Through genetic modifications, key enzymes involved in the phenolic biosynthetic pathway can be introduced into the yeast, enabling them to convert simple precursors into desired phenolic compounds.…”

“…Yeast production: certain strains of yeast, such as Saccharomyces cerevisiae , have been engineered to produce phenolic compounds [ 117 , 118 , 119 ]. Through genetic modifications, key enzymes involved in the phenolic biosynthetic pathway can be introduced into the yeast, enabling them to convert simple precursors into desired phenolic compounds.…”

Polyphenols as Plant-Based Nutraceuticals: Health Effects, Encapsulation, Nano-Delivery, and Application

“…However, some polyphenolic compounds can cause DNA damage at high doses, even to the point of causing apoptosis [ 75 ]. Canedo-Santos et al [ 57 ] showed that the pro-oxidant properties of resveratrol accelerated the aging process and its pro-oxidant activity shortened the chronological life span of brewer’s yeast. In contrast, gallic acid, while inhibiting lipid oxidation and protein carbonyl formation, tends to promote the oxidative loss of thiol and amine groups, thereby affecting the structural properties and biological activity of proteins [ 58 ].…”