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Resveratrol induces mitochondrial dysfunction (in yeast)

resveratrol mitochondrial dysfunction

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#1 ta5

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Posted 14 April 2017 - 10:52 PM


This study sounds interesting. It starts out talking about resveratrol's benefits and the proposed mechanism of action. And then, that mechanism suggests it induces mitochondrial dysfunction and reduces lifespan?? I don't understand.

 

Can someone smarter than me explain this?

 

J Bioenerg Biomembr. 2017 Apr 11. 
Resveratrol induces mitochondrial dysfunction and decreases chronological life span of Saccharomyces cerevisiae in a glucose-dependent manner.

Ramos-Gomez M1, Olivares-Marin IK1, el al.

A broad range of health benefits have been attributed to resveratrol (RSV) supplementation in mammalian systems, including the increases in longevity. Nonetheless, despite the growing number of studies performed with RSV, the molecular mechanism by which it acts still remains unknown. Recently, it has been proposed that inhibition of the oxidative phosphorylation activity is the principal mechanism of RSV action. This mechanism suggests that RSV might induce mitochondrial dysfunction resulting in oxidative damage to cells with a concomitant decrease of cell viability and cellular life span. To prove this hypothesis, the chronological life span (CLS) of Saccharomyces cerevisiae was studied as it is accepted as an important model of oxidative damage and aging. In addition, oxygen consumption, mitochondrial membrane potential, and hydrogen peroxide (H2O2) release were measured in order to determine the extent of mitochondrial dysfunction. The results demonstrated that the supplementation of S. cerevisiae cultures with 100 μM RSV decreased CLS in a glucose-dependent manner. At high-level glucose, RSV supplementation increased oxygen consumption during the exponential phase yeast cultures, but inhibited it in chronologically aged yeast cultures. However, at low-level glucose, oxygen consumption was inhibited in yeast cultures in the exponential phase as well as in chronologically aged cultures. Furthermore, RSV supplementation promoted the polarization of the mitochondrial membrane in both cultures. Finally, RSV decreased the release of H2O2 with high-level glucose and increased it at low-level glucose. Altogether, this data supports the hypothesis that RSV supplementation decreases [chronological life span] as a result of mitochondrial dysfunction and this phenotype occurs in a glucose-dependent manner.

PMID: 28401438


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#2 Supierce

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Posted 15 April 2017 - 12:34 PM

As a  diabetic, this is concerning and seems to contradict virtually all of the research to date. If it's true it would be smart to include a mitochondrial antioxidant in one's daily regimen. Thanks for posting!



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#3 ta5

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Posted 17 April 2017 - 02:23 PM

Here's another one study in yeast that I'm not sure I understand. 

 

Redox Biol. 2017 Apr 9;12:745-754.
During yeast chronological aging resveratrol supplementation results in a short-lived phenotype Sir2-dependent.

Orlandi I1, Stamerra G2, Strippoli M3, Vai M4.

Resveratrol (RSV) is a naturally occurring polyphenolic compound endowed with interesting biological properties/functions amongst which are its activity as an antioxidant and as Sirtuin activating compound towards SIRT1 in mammals. Sirtuins comprise a family of NAD+-dependent protein deacetylases that are involved in many physiological and pathological processes including aging and age-related diseases. These enzymes are conserved across species and SIRT1 is the closest mammalian orthologue of Sir2 of Saccharomyces cerevisiae. In the field of aging researches, it is well known that Sir2 is a positive regulator of replicative lifespan and, in this context, the RSV effects have been already examined. Here, we analyzed RSV effects during chronological aging, in which Sir2 acts as a negative regulator of chronological lifespan (CLS). Chronological aging refers to quiescent cells in stationary phase; these cells display a survival-based metabolism characterized by an increase in oxidative stress. We found that RSV supplementation at the onset of chronological aging, namely at the diauxic shift, increases oxidative stress and significantly reduces CLS. CLS reduction is dependent on Sir2 presence both in expired medium and in extreme Calorie Restriction. In addition, all data point to an enhancement of Sir2 activity, in particular Sir2-mediated deacetylation of the key gluconeogenic enzyme phosphoenolpyruvate carboxykinase (Pck1). This leads to a reduction in the amount of the acetylated active form of Pck1, whose enzymatic activity is essential for gluconeogenesis and CLS extension.

PMID: 28412652


Edited by ta5, 17 April 2017 - 02:23 PM.


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#4 maxwatt

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Posted 17 April 2017 - 05:09 PM

You have to ask about the dose, in this case the concentration of resveratrol in the yeast medium.  Is the concentration greater than anything that could be obtained, say, in mammalian blood serum?  Without doing the math, I suspect these studies involve the equivalent of mega-dosing.   Also, part of resveratrol's action involves apoptosis, as in killing senescent of non-functional cells.  Perhaps oxidative stress is the mechanism that does this.  Killing off non-functioning or weak cells at low doses, and at too high a dose, killing healthy cells.

 

We know that resveratrol concentrations in humans will not reach levels thought to be potentially toxic.  There is a limit to how much can be absorbed orally.  PEpole have been using resveratrol and reporting the effects here since at least 2008.  The only adverse effects noted with any consistence were joint pain in a small number of users,. and possible aggravation of autoimmune diseases.

 

So these studies are probably nothing to worry about.  Still, one never knows.  Monitor your usage, keep a diary.  And were I diabetic, I would consider other substances than resveratrol.  One might want to look into berberine, baicalin and possibly dihydro-myrecetin.  Honokial extracted from magnolia bark is a concentratge of a traditional herbal treatment for diabetes.  Just off the top of my head.


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