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Resveratrol: What’s It Do For Mitochondria?

I’ve been meaning to blog about this new paper in PLOS Biology on resveratrol’s effects on mitochondria. It’s suggesting that the results previously reported in this area cannot be reproduced, namely the idea that resveratrol increases mitochondrial biogenesis and running endurance. In fact, says this new paper, the whole mechanistic story advanced in this field (resveratrol activates SIRT1, which activates the coactivator PGC1, which cranks up the mitochondria) is wrong. SIRT1 has, they say, the opposite effect: it decreases PGC1 activity, and downregulates mitochondria.
That’s an interesting dispute, and leads to all kinds of questions about who’s wrong (because someone certainly appears to be). But there’s another issue peculiar to this new paper. It now says that there are no reader comments, but for a couple of days there was one, which went into detail about how various Western blots appeared to have been performed sloppily and with confusing control lanes. I have no idea how well substantiated these objections were, and I have no idea why they have disappeared from the paper. It’s all quite peculiar.

15 comments on “Resveratrol: What’s It Do For Mitochondria?”

  1. Cell Biologist says:

    I would not blog about this new paper. As you can see, the blots are of very poor quality. The reviewers did a poor job.

  2. sgcgox says:

    There is another recent resveratrol story:
    http://www.sciencedaily.com/releases/2013/07/130722071955.htm
    (I posted this link in a comment to another post, sorry for duplication)

  3. Mike P says:

    For those interested, one more recent article covering the same study as sgcgox’s link:
    http://www.theatlantic.com/health/archive/2013/07/study-anti-aging-antioxidant-actually-seems-to-undo-effects-of-exercise/277993/

  4. Lane Simonian says:

    Certain antioxidants under certain conditions can become pro-oxidants. That is the case with resveratrol. Depending on age, gender, and extent of the exercise, it is possible that resveratrol rather than counteracting the oxidation produced by stressful exercise is actually increasing it.

  5. alig says:

    @2 This is yet another paper showing that antioxidants are harmful if you are exercising. The radicals that form during the oxidative stress are beneficial to health. Stop taking antioxidants if you want to benefit from exercise.

  6. Geneticist says:

    Cell Biologist –
    Sure, some of the blots are a little ugly, and I’d prefer to see a little more of the surrounding membrane. In general though, they’re pretty clear, and not obviously fraudulent – certainly sufficient to support the scientific point being made.
    Do you have a more concrete objection? Which part do you think is insufficient to support the authors’ claims?

  7. Old Surfer Dude says:

    Lane
    Can you provide some examples where certain antioxidants can become pro-oxidants based on age, gender, and extent of the exercise?

  8. Lsne Simonian says:

    There are studies on resveratrol as a potential oxidant (mainly in the presence of copper ions) and studies on strenuous exercise as a cause of oxidation, but I cannot find any studies directly linking the two. The best I can do is to suggest how they might work in tandem. Exercise and resveratrol both activate AMPK. Normally this is positive for human health (AMPK and the biochemistry of exercise: implications for human health and disease). But under conditions of oxidative stress, AMPK increases mitochondrial dysfunction by activating p38 MAPK which leads to the production of peroxynitrites (and may increase the presence of copper ions). So normally exercise and resveratrol would act as antioxidants, but perhaps together they work as oxidants.

  9. Sweden Calling says:

    Resveratrol is dirtier than clozapine….it’s been reported to hit numerous targets. Just sayin

  10. Lane Simonian says:

    But the important question is does resveratrol affect the right targets or the wrong targets. And under certain circumstances can the right targets become the wrong targets.

  11. bob sacamano says:

    coming soon:
    Comment Retraction Watch.com (or perhaps it’s already here)

  12. anonymous says:

    “Move along….nothing to see here….move along”.
    Signed, Christoph

  13. Anonymous says:

    I would agree with Sweeden Calling, Resveratrol is a very dirty compound. Probably developing molecules against targets that are beneficially affected by resveratrol could be a way out.
    About the paper Mike P suggested: Nowhere in the paper do the authors quantify resveratrol’s availability in the blood/plasma. This compound has a very variable/erratic absorption/bioavailability ( a fact that even the authors mention in the paper) from the available OTC formulations… which necessitates a quantification. Nor do they show increases in Sirt1 (a target which resveratrol supposedly activates). Hence, I am not sure I believe in their observations.
    I agree with Lane, maybe an effect similar to scientifically abject concept of hormesis?

  14. V says:

    Anonymous: Probably developing molecules against targets that are beneficially affected by resveratrol could be a way out.
    Well, that exact solution is where the story gets painful as there’s been an outstanding $720M bet on just such a target since 2008.
    Otherwise, I’m in full agreement with you on this paper — not a particular fan of this piece of work.

  15. Paul Brookes says:

    Sorry for not posting this sooner, I was out of town all week and got behind on my reading.
    The comment I originally left at PLoS Biology was removed. The editors contacted me to say they’d like to remove it, which I protested on the grounds that it didn’t breach their comment policy, but they ignored me and did it anyway. That’s why we’re lucky to have sites like PubPeer (http://www.pubpeer.com/publications/D2A46528724F9B59FD58693CA41560) which allow this stuff to remain in the open while the journals do whatever it is they do behind the scenes. As you’ll see from the comment, the western blot data in this paper is a little sloppy.
    The response of the NY Times columnist who ran the big hoopla news story about this, has been to completely ignore me. Similarly, a number of other news outlets who jumped on the media bandwagon about this paper have not responded to requests to modify their stories to indicate the original paper may be flawed. I guess the headline “oops we may have over-hyped something” doesn’t have a good ring to it?

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