Exploring the effects of Dasatinib, Quercetin, and Fisetin on DNA methylation clocks: a longitudinal study on senolytic interventions

I’m still digesting this but the unexpected results seem significant.
aging-v16i4-205581.pdf (1.6 MB)

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Interesting. I’ve been using DQF fortnightly. The Fisetin came as part of the Quercetin supplement, so it was just luck :blush:

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“In the context of our study, the administration of
senolytic drugs Dasatinib and Quercitin significantly
increases biological age”??

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Interesting isn’t it @desertshores. This is why I found the main point unexpected. Of course this is only one study. At the same time, it reinforces how little we know when it comes to human clinical intervention.

The study, though, is worth reading in its entirety for many interesting subpoints.

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Every time I take quercetin or Resveratrol, I get bad diarrhea. I’ve already pitched my Resveratrol. I guess it’s time for the quercetin to go as well. I only feel negatives from it anyways.

I’ll trust my senescent cell fighting to Rapamycin and Taurine.

The science around senolytics is very unsettled. After the initial enthusiasm, it seems to be mostly bad or at least cautionary news. There’s the fisetin failure in the ITP, and studies showing no improvement with their use. It’s likely that in very carefully defined conditions, they may make a positive contribution (perhaps joint health upon direct application, for example), but as a general or mainstay therapy, we know far too little. Everyone makes their own determination of course, but speaking just for myself, senolytics are far too speculative for me and I do not incorporate them in any focused way through supplements and the like. At best, I pay attention to some, such as quercetin, but strictly in my diet. We have different risk tolerance and these exceed my comfort level, while rapamycin, though also quite speculative fits my margins. YMMV.

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IMO, I think it’s a tiny study, with no control group (I,.e. how much older would they have been without intervention?) They aged in the clocks, but they did also age in real life.

The participants changed in some clocks and not others. So the clock stuff is just noise because they don’t give coherent signals.

Plus, I’m not convinced that the circulating markers are even that useful. If senolytics work (I am sceptical), they should be doing so by killing old cells in muscle, cardiac tissue etc. That’s the most convincing mouse data to me, and obviously they can’t biopsy hearts in the human trial.

The biggest damning factor there is that Fisetin failed the ITP, and in fact, nobody has been replicated those studies from one group. As Rich Miller said, when they sent the samples (blinded to the group) back to the lab which proposed it, they couldn’t even see any difference in senescence using a whole bunch of markers. So frankly I’m massively sceptical about the entire premise.

But still, big kudos to this research team for trying to investigate, and for sharing the results. I’m not criticising them at all because I’m sure they are also well aware of these limitations.

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