Tomorrow I will take 10mg together with D&Q and again the day after.
I wouldn't do that. Quercetin would most likely diminish or negate the effects of FOXO4-DRI.
See my previous post[1] on the effects of rapamycin or other anti-inflammatory compounds in combination with FOXO4-DRI.
Now, addressing quercetin specifically:
From [2]:
Quercetin, a natural polyphenol flavonoid, is known to elicit anti-inflammatory ... activities.
...
In vitro, quercetin markedly diminished transcript levels of inflammatory receptors and activation of their signaling molecules (ERK, p38 MAPK, and NF-κB).
...
Together, these findings suggest that quercetin ... inhibit[s] inflammatory receptors and their signaling pathway.
→ source (external link)From [3]:
[Quercetin] has ... antiinflammatory effects.
...
Quercetin suppressed protein levels of the key adipogenic factors C/EBPβ, C/EBPα, PPARγ and FABP4 and the TG-synthesis enzymes lipin1, DGAT1 and LPAATθ. Activation of m-TOR and p70S6K, which are related to insulin and adipogenesis, was down-regulated during adipogenesis in 3T3-L1 cells.
...
Our data showed that quercetin inhibited the MAPK signaling factors ERK1/2, JNK and p38MAPK and MCP-1 and TNF-α in adipocytes and macrophages. Quercetin also inhibited secretion of the inflammatory cytokines IL-1β and IL-6 and stimulated that of IL-10, an antiinflammatory cytokine.
→ source (external link)From [4]:
Results indicated that quercetin was able to ameliorate all markers of inflammation and oxidative stress measured. Quercetin lowered levels of interleukin-1β, C-reactive protein, and monocyte chemotactic protein-1
...
Finally, quercetin inhibited the 2-fold increase of NF-қB activity observed in lung, liver and joint after induction of arthritis.
→ source (external link)Per all of the above, quercetin is inhibiting at least six different molecules involved in autocrine and/or paracrine signaling of SASP in various cell types.
Blocking the IL-1 receptor or inhibiting mTORC1 have already been directly empirically shown to negate senolytic activity of FOXO4-DRI. (See my previous post[1] for references.)
Inhibiting p38MAPK is known to shut down SASP, and would most likely have a similar effect[5][6][7][8]. I would expect the same with C/EBPβ[9]. And IL-6 is part of the SASP feedback loop as well[9].
And you're hitting all of these, either directly or indirectly with quercetin. Even if most of the action is indirect (most likely), the fact that the particular combination of proteins/cytokines mentioned above is being inhibited only serves to demonstrate that in all likelihood quercetin is successfully disrupting the signaling loop underlying SASP.
SASP signal transduction:
As for combining dasatinib, I'm not sure that's a good idea either. There's some indication it could have similar effects, though it's not as clear in this case as it is with quercetin. I see mentions of it reducing various cytokines in some circumstances[10][11][12]. And Src Tyrosine Kinase (which dasatinib inhibits) upregulates p38MAPK[13].
Just taken my first 5mg dose. Only observation so far is that the injection site hurts which is probably a reaction between the FOXO and surrounding tissue.
Doubt it's a reaction to FOXO4-DRI. The peptide is in HCl salt form (once in solution, the HCl should dissociate nearly completely). What volume of PBS did you use to dilute this 5 mg of peptide? I'm guessing you didn't use enough PBS to bring the solution close enough to neutral pH.
After a week, I will start using Rapamycin again.
Smart. I think waiting the full week is best.
After reviewing at Figures 2N and 3H in the main FOXO4-DRI paper[14], it looks like quantity of phosphorylated p53 in the cytosol (for use in the intrinsic apoptotic pathway) doesn't really peak until 48 hours post-dose, and then caspase levels keep rising until 60 hours post-dose. So it would probably be wise to add some additional buffer time to the 96 hour minimum waiting period I previously suggested. I would wait at least a week before resuming rapamycin use.
References:
