Fisetin to Clear Senescent Cells

Hello everyone,

I'm new here but not new to anti-aging and longevity.  I've read the 500+ replies above and it's all good stuff. Great community of like-minded people. Glad to be here.

I've been experimenting with NAD+ boosting compounds, not only the precursors mind you but also CD38 inhibitors, AMPK and NAMPT boosters etc... in the hopes of restoring the cells' ability to make its own NAD+ again...

This is all well and good but then something dawned on me during this experimentation, while I was reading about senescence, autophagy and related matters, that removing senescent cells (with compounds such as Fisetin for example) should be the primary objective here, especially when one is at an advanced age, rather than inhibiting and boosting certain enzymes to, in essence, block the toxic effects of zombie cells on the healthy cells.

It's like storing rotting food waste and garbage all over your house for years, never removing it and then buying a couple of HEPA filters to take care of the smell. I say clear out the garbage first.

Am I on the right track?

If I understand correctly, just the removal of a small portion of these toxic senescent cells, reduces CD38 expression and actually restores NAD+ production (even in older organisms), not to mention the reduction of chronic inflammation and many other problems associated with these zombie cells, hence your body behaves as if it were younger. If these are purged from the system via the senolytics of course.. 

I mean rather than use compounds such as Apigenin and Quercetin for the specific purpose of CD38 inhibition, wouldn't it be a lot better to actually go to the source of the problem and effectively purge those nasty zombie cells in the first place and keep them in control?

Having accomplished that, your NAD+ levels would presumably return to normal and there would be no more chronic inflammation and poisons affecting the healthy cells, once you take care of the toxic senescent cells. 

I am still unsure if I should keep on the NAD+ boosting compounds, which can be expensive or move over to the "hit and run" Fisetin dosing to manage my senescent cells which, my intuition tells me, can possibly be more effective and less expensive too...

Actually, let me asking you a question.. If you had to pick one thing you'd do, the NAD+ boosting compounds, as I have laid out above, or senolytics? Which would you choose?

Sorry for the long post but I do have another question too: I am aware of the Mayo Clinic Fisetin protocol dosing but is there any data (even anecdotal) that a lower dose, for example 500 mg/day, for a longer period of time, for example for 5 days or a week, every month, would be effective and worth trying, to purge these zombie cells? I am of course planning to mix the Fisetin with some type of fat for better absorption. 

Thanks for reading and I welcome any thoughts that you may have,

Dan

Here is an excerpt from the article on the grapefruit juice effect on sirolimus. I didnt realize that the effect begins within a few hours of ingesting the juice. I thought it was faster than that.

"Consuming 8 ounces of grapefruit juice increases sirolimus levels by 350%, allowing persons with cancer to take less toxic doses of the drug.        

This information was obtained from three simultaneous phase 1 studies involving 138 persons with advanced cancer. The trials employed an adaptive escalation design to find the doses of oral, weekly sirolimus alone or in combination with either the antifungal agent ketoconazole or grapefruit juice that would achieve similar blood concentrations as temsirolimus, the intravenously administered and approved prodrug of sirolimus.

An mTOR inhibitor, sirolimus is approved to help prevent organ rejection in transplant recipients, but may have anticancer effects as well. Grapefruit juice inhibits intestinal P450 enzymes that break down sirolimus as well as several other drugs.

According to a statement from the University of Chicago Medical Center in Chicago, Illinois, where study director and cancer specialist Ezra Cohen, MD, practices, the effect of grapefruit juice begins within a few hours of ingestion and wears off gradually after a few days. Although this effect has long been considered an overdose hazard, “We wanted to see if grapefruit juice can be used in a controlled fashion to increase the availability and efficacy of sirolimus,” explained Cohen in the statement."