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Aging and Lifespan

Ibuprofen For a Longer Life?

Here’s one that I didn’t expect: a report that ibuprofen extends lifespan in model organisms.

Here we show that ibuprofen increased the lifespan of Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster, indicative of conserved eukaryotic longevity effects. Studies in yeast indicate that ibuprofen destabilizes the Tat2p permease and inhibits tryptophan uptake.

Now, as it happens, there are other compounds that disrupt Tat2p – quinine, for one. Does that one increase lifespan? You apparently can’t get fruit flies to eat it (not surprisingly), and I can’t find any studies on yeast lifespan with it. This sort of thing would be a useful follow-up. It’s worth noting that another tryptophan pathway (inhibition of its conversion into kynurenine) has also been implicated in longer lifespan in fly models, which might be another thing worth checking up on.
The big question, naturally, is what relevance this has to humans. As the paper notes, there is a study saying that a low-tryptophan diet prolongs the lifespan of mice. But there are complications as well:

We also noted that the effective pro-longevity concentrations of ibuprofen were much lower in flies than in worms or yeast (0.5 µM vs. 100–200 µM, respectively; see Fig. 1). The reason for this difference is unclear at present. In healthy humans who took a 600 mg ibuprofen dose up to four times daily, the peak plasma concentration was around 50 µg/ml, corresponding to 240 µM [56]. In another study, a single 400 mg dose of ibuprofen results in a plasma concentration of 8.4 µg/ml, or 40 µM [57]. Therefore, the levels of ibuprofen that extend the lifespan of worms and yeast are in the range of ibuprofen levels reached in people taking the drug at typical doses. Overall, our results add to the growing role of NSAIDs, and ibuprofen in particular. These compounds are relatively safe therapeutics that may combat age-related pathologies and extend the lifespan of divergent organisms, from yeast to invertebrates and possibly mammals.

That dose/response is interesting, and needs to be followed up on. Another odd effect was seen in male Drosophila, whose maximum lifespan was actually reduced a bit (although the mean might have gone up a bit). There’s a human amino acid transporter condition (Hartnup disorder), which seems to pretty much wipe out tryptophan uptake from the gut, but it also affects a number of other neutral amino acids. (Patients remain normal on a protein-rich diet, probably through uptake of oligopeptides). But there appear to be several human tryptophan transporters, and since I’m writing this from the middle of my vacation, I don’t have any idea if any of them are homologs to Tat2p. (I’m probably getting way too much tryptophan during this break, anyway – those gingersnaps are doubtless full of the stuff).This new PLOS Genetics paper doesn’t mention any such homolog, and you’d figure that they would if there were a direct comparator. So we shall see – for now, this gets filed in the “interesting” category.

16 comments on “Ibuprofen For a Longer Life?”

  1. Marc Bemis says:

    I wish I had a link to back this up, but I recall learning about the negative cardiac influences of long term NSAID use. I consistently tell patients to speak to their doctor’s about alternative pain medications for chronic pain because of this. Food for thought.

  2. Tommy says:

    would be one of many many studies/reviews on that topic. And you are totally right, the long-term use of (all afaik?) NSAID is linked to an increased cardiovascular risk.

  3. Anonymous says:

    This gives me even more reason to continue my nightly wine (resveratrol) and subsequent morning ibuprofen regimen. I will live forever!

  4. Paul D. says:

    Have genetic studies of people who reach very old age (100+) revealed anything interesting?

  5. anonymous says:

    #3: I prefer my morning wine and nightly ibuprogen.

  6. Anonymous says:

    A few years ago, I read in a wall Street Journal article that three sisters who lived beyond 100 years had their HDL cholesterol levels above 100. A link of ibuprofen (advil, etc) to cardiovascular risk (QT prolongation) was issued by FDA a few years ago when cox inhibitors were withdrawn (vioxx). Today Novartis has reported that mTor inhibitors impart longevity.

  7. Ann O'Nymous says:

    How long until the ridiculous Dr. Oz-style claims start appearing? “try this one weird tip to live longer”.
    Oh wait, they already have:
    Worse, this sort of nonsense is being fed by PR from the organization where the researchers worked.
    Bah humbug.

  8. Anonymous says:

    Noise, noise, everywhere. I used to like science, back when there was a little bit of signal.

  9. anon says:

    System L transporter seems to be used for most Trp transport, EXCEPT in the gut, where SLC6A19 (a system B(0) transporter) predominates and its mutations associate with Hartnup.
    System L transporter is an anticancer target, since many tumors import huge amounts of large neutral amino acids as energy sources, along with glutamine (mostly via Asct2).

  10. Erebus says:

    It might be worth noting that a recent study claims that tryptophan supplementation in rats improves body composition and, ostensibly, overall health. PMID: 25139634
    In any case, if the results with ibuprofen can be duplicated with quinine, it looks like gin ‘n tonic might also be a longevity-enhancing beverage…!

  11. London Chemist says:

    Yeast doesn’t have a kidney: I believe ibuprofen is nephrotoxic (and is so banned to people with CKD or transplanted kidneys).

  12. DN says:

    I have no citations, but IIRC aspirin reduces cardiovascular risk, naproxen is nearly neutral, ibuprofen has a moderate risk, and the other NSAIDs range from moderate to severe.

  13. Anony-brain says:

    “We also noted that the effective pro-longevity concentrations of ibuprofen were much lower in flies than in worms or yeast (0.5 µM vs. 100–200 µM, respectively; see Fig. 1). The reason for this difference is unclear at present.”
    Concentrations where?
    Are these nominal concentrations in the dosing solutions?

  14. anon says:

    I had a nasty allergic reaction to naproxen taken for a running injury, so NSAIDs are out… looks like no extended lifespan for me. 🙁

  15. Vader says:

    “Noise, noise, everywhere. I used to like science, back when there was a little bit of signal.”
    But at least it’s entertaining!
    Even if, as science, it’s absolute crap.

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