I’m glad to see epicatechin had a life-extending effect after all, however small. Maybe there’s a similar compound with even more potent effects.
I’m looking forward to hearing how GlyNAC turns out. Neuro-NAC might be an even more powerful supplement to try for life-extending purposes.
I also will test out black ginger to see its effects. (A personal n=1 test).
I wonder about EGCG, also. It has been claimed to inhibit DYRK1A, one of the genes influencing the DREAM Network (so does EGCG result in an increase in DNA repair?), though I’m not sure the same is true of plain epicatechin.
Interesting
- it improves mitochondrial dysfunction, potentially even more than aerobic training
- redistributes fat from muscles and beta cells to subcutaneous fat
- is the only drug that increases insulin sensitivity
The results from the ITP (Intervention Testing Program) can absolutely be seen as a strong signal that excessive insulin signaling (hyperinsulinemia) is a key accelerator of mammalian aging. This aligns very well with Dr. Ben Bikman’s reasoning and the broader scientific understanding of the insulin/IGF-1 signaling pathway in aging. Insulin levels can be seen as the canary in the coal mine.
ITP, some of us here and biogerontologists know that the Insulin/Insulin-like Growth Factor 1 Signaling pathway is one of the most evolutionarily conserved pathways regulating aging. Reduced signaling in this pathway is strongly associated with increased lifespan and healthspan in species from worms and flies to mice. And some say that, low insulin signals is strongly associated with increased lifespan and healthspan even in long lived humans.
Excessive signaling is associated with accelerated aging and age-related diseases.Insulin is Not the Enemy, Hyper-insulinemia Is. Insulin is an essential anabolic hormone. We need it to live. The problem is the chronic, excessive levels. The ITP provides strong correlative signal for this reasoning.
But these drugs (drugs for type 2 diabetes) have other proposed anti-aging effects, like effects on mitochondria, AMPK activation, that may be independent of insulin. Lower insulin likely contributes to these other beneficial effects. High insulin activates besides IGF also mTOR.
Other concentrations will need to be tested, but based on the available evidence, acarbose is the antidiabetic drug with the greatest impact on lifespan in mice and with fewer potentially harmful side effects.”
What is the it?
Epicatechin has some HDACi activity.
You can always follows the arrows on the F Forum when things are linked, here it is
In this episode from today, Ralph DeFronzo says the following about Pioglitazone:
- it is the best drug for treating NASH.
- it improves mitochondrial dysfunction, potentially even more than aerobic training
…
I tried that. It did not tell me
I have looked at Pioglitazone using chatGPT. It is not entirely clear how this works. It may be useful.
I have been eagerly awaiting the forskolin results, as I take it as part of my bone building regimen and I wanted reassurance that it isn’t negatively affecting my longevity, as there seem to be no previous experiments where mammals have been fed forskolin for their entire life. I got that reassurance, at least, but looking deeper, it seems they tested it at a relatively low concentration of 8ppm in the chow, which translates to a significantly lower dose than many people take. 8ppm translates to less than 1 mg/kg/day, yes? I take 100 mg/day. They state in the paper, “We note, however, that FSK increased median survival of males by ~ 8%, although this did not reach statistical significance. It is possible that testing FSK at other doses might produce more impressive effects.”
Not at all. These are very different drugs. Pioglitazone is an old drug well known to act through activating PPARgamma. Mitoglitazone does not activate PPARgamma at all (at least not directly and probably not indirectly either to a significant extent). The fact that they both share the glitazone nomenclature can be misleading because it is a reflection of their similar chemical structure rather than of their mechanism of action. Similar chemical structure does not mean similar mechanism of action however.
Yes, try Ghirardell intense dark chocolate 85%
Yes and no in this case. Pio (and I think the rest of the common glitazones) hits both the mitochondrial target and PPARg. The antidiabetic effect is speculated to come from both sources. Mitoglitazone is a tiny structural modification of Pio that somehow disables the PPAR activity, without being notably more or less active at the mpc, iirc.
I think I heard Rich Miller mentioning they wanted to include it but stability was an issue. Now that brands like prostaphane have a stabilised form I wonder if they will consider using that.
Article on the synergy between EGCG and quercetin:
We previously demonstrated that 50% of (−)-epigallocatechin gallate (EGCG) was present in methylated form (4″-MeEGCG) in human prostate tissue, which is less bioactive. We therefore investigated whether quercetin, a natural inhibitor of catechol-O -methyl transferase (COMT), will inhibit EGCG methylation leading to enhanced antiproliferative activity of EGCG in prostate cancer cells. Incubation with both, quercetin and EGCG, for 2 hr increased the cellular concentrations of EGCG by 4 to 8-fold and 6 to 10-fold in androgen-independent PC-3 cells and androgen-dependent LNCaP cells, respectively.
I don’t know whether that’s good or bad. It’s good if we’re talking about prostate cancer; but maybe bad if we want more methylated EGCG that stays in the body longer (it’s less active form of EGCG, but on the other hand, it lasts a lot longer).
One wonders what would happen if you gave mice not only EGCG but also some quercetin. Would it increase the lifespan-extending effects of EGCG?
There are both KDACi s. (a more generalised form than an HDAC i)
Quercetin seems to be. But following a quick Internet search (Google) it seems a bit inconclusive for EGCG.
https://claude.ai/share/90240dd1-051c-4fff-8ebc-431161b00975
Overall assessment: While EGCG does influence histone acetylation status and has been called an “HDAC inhibitor” in some literature, the mechanistic evidence suggests it functions primarily as a HAT inhibitor with possible weak, indirect effects on HDAC activity. The term “HDAC inhibitor” may be a misnomer for EGCG, though it does ultimately affect the acetylation balance in cells.
Everything body talks about glitazone.
But what about saroglitazar??
Same effectiveness, no sides, and lower lipids!
