Rapamycim vs dasatinib vs quercetin/theaflavins
Hi Folks , I’m new here. Can you comment on the differences and benefits of each approach?
How about the combo of rapamycin and the quercetin/theaflanins?
I have most things going well (10 years of metformin/aspirin, weight loss, exercise, good diet). I’m ready for the next stage, but unsure of which.
What would you suggest? Why?
Thank you!
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The current suggested order of things can be found under the Research header above. What is not mentioned is the need to get a good testing baseline so you can tell if things are working. LEf.ORG sells a comprehensive set of test at a discount many are using for this baseline. You can find it here: https://www.lifeextension.com/Lpages/2018/INE801E/index
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There is currently no evidence at all that theaflavins selectively kill senescent cells: if you read the article in the magazine or on the website, they're just basing the product on studies showing that theaflavins kill cancer cells in a Petri dish via some of the same pathways that senolytic drugs hit, and guessing that the same thing will happen to senescent cells after you take it in supplemental form. We don't know that theaflavins can selectively kill senescent cells even in a Petri dish, or if they hit those same pathways in cells in the body after you take it in pill form (since we don't know if you absorb enough to reach the needed concentration, or if theaflavins are metabolized into a metabolite that is sufficiently different from the parent theaflavin molecule that it loses this activity).
We also don't really know if quercetin kills senescent cells when taken without dasatinib:
https://www.fightaging.org/archives/2018/01/quercetin-is-probably-not-a-useful-senolytic/
Dasatinib + quercetin definitely does kill senescent cells in supplemental form in mice — but dasatinib is also a much more dangerous drug than Q or theaflavins. And we don't know for sure that it will work as a senolytic in humans as it does in mice, though there are certainly some striking anecdotes coming out.
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Question from a simple layman. But how can we measure if senolytic(s) of choice remove more senescent cells than healthy cells ? My worry ! Or is it ill founded ?
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Seaside Senescent cells release inflammatory cytokines and other nasties, so if we were to measure the 'senolytic poison load' on your system presumably we'd know the amount of senescent cell load you have, and the change from taking senolytics.
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DanMcL Seaside I don't believe that circulating cytokines are reliable indicators of senolytic activity ... there was no clear effect on these in the recent dasatinib + quercetin clinical trial for idiopathic pulmonary fibrosis, despite good dosing and a very high burden of senescent cells in these patients, and similarly the UNITY trial is relying on cytokines from aspirated synovial fluid lavage, which they would surely not do if they were getting a signal in the circulation. Also fisetin may affect inflammation through mechanisms other than senolytic activity, which would create a false positive.
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Thanks DanMcL
