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Super interesting interview presentation with Mayo Fisetin Study lead scientist James Kirkland.
https://www.youtube.com/watch?v=0mD-wupqvQE

Some points that stood out to me:

• He says it's still possible that removing senescent cells may play both positive and negative roles in ways we don't yet understand
• He actually isn't confident that this is safe yet. They are only attempting to treat fairly frail/sick individuals in the trials who have no better options, but does not recommend it to healthy people because there are too man unknowns
• He thinks this "hit and run" approach (large occasional doses) is the way to go with senolytics and does not think daily dosing is a good idea
• Fisetin doesn't kill the cells, but instead interrupts the protective capacities of the senescent cells which allows them to be killed though normal processes

rhett wrote: ↑Fri Jul 16, 2021 3:09 pm Super interesting interview presentation with Mayo Fisetin Study lead scientist James Kirkland.
https://www.youtube.com/watch?v=0mD-wupqvQE

Some points that stood out to me:

• He says it's still possible that removing senescent cells may play both positive and negative roles in ways we don't yet understand
• He actually isn't confident that this is safe yet. They are only attempting to treat fairly frail/sick individuals in the trials who have no better options, but does not recommend it to healthy people because there are too man unknowns
• He thinks this "hit and run" approach (large occasional doses) is the way to go with senolytics and does not think daily dosing is a good idea
• Fisetin doesn't kill the cells, but instead interrupts the protective capacities of the senescent cells which allows them to be killed though normal processes

Very interesting interview.  I understand his conservative approach in discussing Fisetin, but phase I trials deemed it safe in the large, hit and run doses needed to induce apoptosis in senescent cells.  He's right, we don't know if it's eliminating the good senescent cells, too.  

The other point to make is that there are a large number of people who have replicated the Mayo Clinic Fisetin protocol with no negative side effects.  This is of course anecdotal evidence and everyone should use their own due diligence as we all know in the biohacking community.
 

Absolutely, I've done the hit and run fisetin dosing from the trial about 5 times myself, no obvious ill effects to speak of. I think the theoretical concern I've heard some wonder about is that since killing off senescent cells requires stem cells to jump in and replicate to replace them, is it possible that there is a benefit in the short term, but a negative effect long term if that stem cell splitting means stem cell telomeres get shortened by extra replication.

There's an article by SENS that argues that running out of telomere length for this reason isn't a concern during normal human lifespans.  It seemed like a good argument to me, and certainly one I'd like to believe after doing this 5 times already! But I think the fact remains is we don't really understand the full implications of senolytics. 

Not a definite warning sign, just a reminder that there's still more to learn. 

I was reading about Quercitin that it can perform repair to DNA in some cells:

So if we see Senolytics with this additional function, that is excited.

https://pubmed.ncbi.nlm.nih.gov/19651184/


https://www.dovepress.com/quercetin-sup ... rticle-OTT