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.