Aspirin Pro-Drug From Willow Bark Extends Yeast Lifespan By Almost 400%

haidut

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I don't know if the active ingredient in willow bark that is responsible for this lifespan extension is salicylic acid, but it is very likely given the increase in metabolism of yeast given the willow bark extract. It is worth noting that willow bark extract was the most potent of all 10,000+ ingredients with lifespan extension features that the team tested. It is also worth noting that the extract extended both average and maximum lifespan several-fold, and it is the latter that is the goal of most anti-aging research.
Btw, there are several other studies showing lifespan extension from aspirin and pure salicylic acid. I have already posted some of them on the forum.
The willow bark extract (PE21) was standardized for 25%+ salicin, which is a pro-drug for salicylic acid and has action very similar to aspirin.
Salicin - Wikipedia, the free encyclopedia
The concentration that had the strongest life extending effect was 0.1% of the extract as part of the diet. I emailed the authors and the response I got was that the human equivalent dose of would be 41mg/kg and 82mg/kg of the willow bark extract, which was standardized to 30% salicin. So, this means 12.5mg/kg or 25mg/kg salicin for a human daily. Now, salicin is a prodrug for salicylic acid just like aspirin, but the good news is that you need less aspirin to get the same levels of salicylic acid than by ingesting salicin. The coefficient is about 0.63 for aspirin, so the above doses of salicin would equate to about 7.9mg/kg and 15.75mg/kg aspirin daily. This corresponds pretty well to the optimal therapeutic aspirin doses seen clinically - i.e. 500mg - 1,500mg daily.
http://www.epsce.com/userfiles/A Novel More Potent Salicin Content.pdf
"...A typical 500 mg dose of aspirin is equivalent to 794 mg of salicin [7]. To round off these numbers, 800 mg of Salicin is equivalent to 500 mg of Aspirin; it will take approximately 38 drops of White Willow buds to equal the 500 mg of aspirin and 19 drops as an alternative to 250 mg of aspirin. All of this is just an approximation and not an exact certification but helps us how to gauge therapeutic levels."
Reference [7] from above quote: Rational Phytotherapy: A Physicians' Guide to Herbal Medicine | Annals of Internal Medicine

While there were several mechanisms of action at play, one of the most important lifespan extending mechanisms was the increase in mitochondrial respiration and ROS production.

http://medicalxpress.com/news/2016-03-youngand-alive.html
"...One of these groups of molecules is the most potent longevity-extending pharmacological intervention yet described in scientific literature: a specific extract of willow bark. Willow bark was commonly used during the time of Hippocrates, when people were advised to chew on it to relieve pain and fever. The study showed that it increases the average and maximum chronological lifespan of yeast by 475 per cent and 369 per cent, respectively. This represents a much greater effect than rapamycin and metformin, the two best drugs known for their anti-aging effects. "These six extracts have been recognized as non-toxic by Health Canada, and already exhibit recognized health benefits in humans," says Simard. "But first, more research must be done. That's why Idunn Technologies is collaborating with four other universities for six research programs, to go beyond yeast, and work with an animal model of aging, as well as two cancer models."

Discovery of plant extracts that greatly delay yeast chronological aging and have different effects on longevity-defining cellular processes | Lutchman | Oncotarget
"...We found that each of the six lifespan-extending PEs stimulates coupled mitochondrial respiration, which was monitored by measuring the rate of oxygen consumption by yeast cells. PE4, PE8 and PE12 decreased the extent to which such respiration declined in ST-phase cultures (Figure 5A, 5D and 5E), whereas PE5, PE6 and PE21 considerably increased the rate of mitochondrial respiration in yeast during PD and ST growth phases (Figure 5B, 5C and 5F)."

"...In this study, we performed a screen for PEs capable of extending longevity of the chronologically aging yeast S. cerevisiae. Our screen revealed six PEs (which we call PE4, PE5, PE6, PE8, PE12 and PE21) that can significantly increase yeast CLS. We demonstrated that each of these PEs is a geroprotector which delays the onset and slows the progression of yeast chronological aging by eliciting a hormetic stress response. We provided evidence that each of these geroprotective PEs has different effects on cellular processes known to define longevity in organisms across phyla. Such effects include the following: 1) amplified mitochondrial respiration and membrane potential; 2) increased or decreased concentrations of ROS; 3) reduced oxidative damage to cellular proteins, membrane lipids, and mitochondrial and nuclear genomes; 4) enhanced cell resistance to oxidative and thermal stresses; and 5) accelerated degradation of neutral lipids deposited in LDs (Figure 13). These findings provide important new insights into mechanisms through which some chemical compounds of plant origin can slow biological aging."

"...Specifically, both these pharmacological interventions were demonstrated to increase the RLS and/or CLS of yeast and human peripheral blood mononuclear cells by 83%–200%; the corresponding rows in Table S1 are highlighted in green. Of note, PE21 appears to be the most potent longevity-extending pharmacological intervention presently known. It increases the mean and maximum CLS of yeast by 475% and 369%, respectively (Figure 3A and 3B; Table S1)."
 
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haidut

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i wonder if it induces uncoupling...

I would depend on the dose. If there is no conversion factor and HED is really 1-2 tablets of aspirin then uncoupling is probably not involved. But one of the proposed mechanisms is the increased generation of ROS, and that usually happens during uncoupling.
 

tara

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So ... aspirin extends the life of yeasts and also helps kill off candida?
 

haidut

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So ... aspirin extends the life of yeasts and also helps kill off candida?

Lol, weird right? It may depend on the dose. The salicylic acid dose that kills Candida is 1mM+, which is achievable by ingesting 3g+ aspirin. I don't think the yeast got that much salicin, it was probably much less but I am waiting on confirmation from the study authors.
 

haidut

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Haidut, why not advice to use Willow Bark powder instead of Aspirin?

Sure, if that's what people prefer. The study hints that it is actually salicin that is responsible for these effects and it is important to know what is the active ingredient since not everybody has access to willow bark extract. If it is indeed salicin to "blame" than it would also add further weight to the studies on aspirin for Alzheimer and reversing aging by reversing inflammation.
 

Parsifal

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Lol, weird right? It may depend on the dose. The salicylic acid dose that kills Candida is 1mM+, which is achievable by ingesting 3g+ aspirin. I don't think the yeast got that much salicin, it was probably much less but I am waiting on confirmation from the study authors.

So if one is not taking 3g+ of aspirin it will make their yeast grow?
 

haidut

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I updated the original post with human dose estimates that I got from the paper author. Basically, the two doses that they found effective were equivalent to a human dose of 41mg/kg and 82mg/kg of the willow bark extract, which was standardized to 30% salicin. So, this means 12.5mg/kg or 25mg/kg salicin for a human daily. Now, salicin is a prodrug for salicylic acid just like aspirin, but the good news is that you need less aspirin to get the same levels of salicylic acid than by ingesting salicin. The coefficient is about 0.63 for aspirin, so the above doses of salicin would equate to about 7.9mg/kg and 15.75mg/kg aspirin daily. This corresponds pretty well to the optimal therapeutic aspirin doses seen clinically - i.e. 500mg - 1,500mg daily.
http://www.epsce.com/userfiles/A Novel More Potent Salicin Content.pdf
"...A typical 500 mg dose of aspirin is equivalent to 794 mg of salicin [7]. To round off these numbers, 800 mg of Salicin is equivalent to 500 mg of Aspirin; it will take approximately 38 drops of White Willow buds to equal the 500 mg of aspirin and 19 drops as an alternative to 250 mg of aspirin. All of this is just an approximation and not an exact certification but helps us how to gauge therapeutic levels."
Rational Phytotherapy: A Physicians' Guide to Herbal Medicine | Annals of Internal Medicine
 

Literally

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I use Willow Bark - not the extract but the actual bark, in my tea regularly. I love it, but wanted to pass on a word of caution. A few times I used too much of it and got black and red spots in my eyes -- like a hallucination sort of but more likely caused by circulation issues. The stuff is potent... I only put a small amount in my herbal teas now and don't have that problem. But I am a big dude and it still didn't take much. I would start with no more than half a teaspoon of the bark and then work up to maybe a few teaspoons max.

The Willow Bark is very easy to find here locally, not only on the trees but my health food store carries it from Frontier Organic in a big jar.
 

Cameron

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Seems grandmas using daily aspirin I know are living well into there 80s and 90s. My grandma is a high carb dieter baking soda and many years of aspirin and dairy. She is single lives a lone travels with friends and is and 86 year old that looks and acts 50! Also grew up eating liver but now a lot more PUFA but still butter eggs and sugar and she’s in better shape then my mom.
 

Sativa

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Wow, thanks for that juicy bit of info!

"...aspirin can also activate AMPK (91).
AMPK inhibits mTORC1 activity through two independent mechanisms"


What is AMPK, why is it SO relevant to Peat domain?
AMPK is the major energy status sensor that promotes catabolic pathways that generate ATP and inhibits anabolic pathways that consume ATP. A low ATP/ADP ratio activates AMPK resulting in its phosphorylation, leads to decreased activities of pathways that consume energy (anabolic pathways) and increased activities of pathways that produce energy (catabolic pathways)

IIRC, Curcumin activates AMPK, as well as 5-HT1A that dampens/reduces the activity of all other serotonin receptors.

The well-known drug ketamine also works via AMPK & mTOR...

Title: The activation of AMPK in rat hippocampus contributes to the rapid antidepressant effect of ketamine.
...In conclusion, our results suggest that the activation of AMPK in rat hippocampus is involved in the procedure of ketamine exerting rapid antidepressant effect through the up-regulation of BDNF.
From another paper...
...we next wanted to investigate whether AMPK is affected by ketamine treatment.
-
...our observation of an increased AMPK activation following ketamine treatment.
-
We propose that ketamine treatment causes a cellular energy deficit by first promoting anabolic processes (that consume ATP) through the activation of mTORC1. This is counterbalanced in a second phase by the activation of AMPK that promotes catabolic pathways (to generate ATP).

Ketamine is currently a top favorite as a pharmaceutical anti-depressant... and is widely self-administered by members of the public for it's pro-metabolic & anti-cortisol properties.
Haidut mentioned one aspect here... Aspirin Is An Anti-depressant As Effective As Pharma Drugs
 
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