The Most Potent Life Extension Substance Ever


Plant extracts more potent than metformin and rapamycin

Recently, a research group screened a number (37 to be exact) of plant extracts to see what effect they might have on slowing aging and extending life. They say they’ve found the most potent life extension substance ever.

The screening was done by adding these substances to the growth medium of the yeast Saccharomyces cerevisiae, which is the same yeast used to make wine and beer, and which is often used in aging studies. Yeast cells have biochemistry similar to mammalian cells, they age and die similarly to mammalian cells, their lifespans can be increased by calorie restriction, they are cheap experimental animals, and their lifespans are short, all of which make them ideal for aging experiments and especially, screening of a large number of compounds. The paper is “Discovery of plant extracts that greatly delay yeast chronological aging and have different effects on longevity-defining cellular processes”, published in Oncotarget.(1)

An news write-up in Science Alert (2) stated:

“In total, we found six new groups of molecules that decelerate the chronological ageing of yeast,” said biologist Vladimir Titorenko from Concordia University.

As the authors report in Oncotarget, one of these compounds – a specific extract of willow bark (Salix alba) – is the most potent longevity-extending pharmacological intervention ever described in scientific literature. In testing, the willow bark extract increased the average chronological lifespan of yeast by 475 percent and the maximum chronological lifespan by 369 percent.

If these findings can be replicated in something other than yeast, it’s a major discovery, outperforming the anti-ageing effects of both rapamycin and metformin. And in addition to slowing ageing, the compounds may also have beneficial effects on cellular processes when it comes to preventing related diseases, such as cancer, the researchers say. The other extracts come fromCimicifuga racemosa, Valeriana officinalis L., Passiflora incarnata L., Ginkgo biloba,and Apium graveolens L.. [My emphases.]

These compounds may be much more potent than the two most widely touted anti-aging drugs, rapamycin and metformin.

Willow bark was the most potent extract, extending lifespan 5-fold

What really caught my eye was that the most potent substance they found was an extract of willow bark. This the same source from which aspirin was derived.

Willow bark contains salicin, which when metabolized in the body becomes salicylate, an anti-inflammatory and pain-killing chemical. In the new paper, the potent life-extending willow bark extract contained “>25% salicin”.

The technical name for aspirin is acetyl salicylic acid (ASA). When metabolized, the acetyl group is split off, and the active pain-killing substance, salicylate, is generated. (Aspirin has two modes of action: the anti-platelet (“blood-thinning”) action comes from the acetylation of platelets; the pain-killing mode from salicylate.)

So, we see that there’s a huge point of similarity between aspirin and the willow bark extract that extended lifespan. Of course, there may be other compounds in willow bark besides salicin that are important – we just don’t know at this point. There’s even a possibility that salicin is irrelevant to the extract’s effects, though that seems very unlikely, as I’ll explain.

How much did this extract with >25% salicin extend yeast lifespan? See the following chart.


plant extract

In the chart, the willow bark extract is PE21, at the bottom. The top, black bar is the control yeast, with no plant extract added to the medium. Willow bark extract extended yeast lifespan by almost 5-fold, making it the most potent life-extending substance yet found, eclipsing metformin and rapamycin.

Importantly, as the chart shows, the yeast were grown in 2% glucose, i.e. were not food restricted. When cells were grown in calorie-restricted conditions — 0.5% glucose — all the extracts were much less or even not at all effective. This shows that a major mode of action of these substances is by mimicking calorie restriction, presumably by activating the same biochemical pathways.

Aspirin extends lifespan

If salicin in willow bark is wholly or partially responsible for its life-extending power, then aspirin could also be one of the most potent life-extending drugs known.

We already know that aspirin extends lifespan in mammals (mice) and in C. elegans (a worm). So the fact that salicin was involved in the present study is unlikely to be a fluke.

Aspirin also extends lifespan in another experimental animal, the cricket.(3) Not only did it extend lifespan, but it was much more potent than metformin in doing so, and showed very few life history trade-offs in life extension. In other words, metformin, while it extends lifespan, also significantly impairs growth and rate of maturity, while aspirin does not.

Unlike the reigning dietary restriction paradigm, low aspirin conformed to a paradigm of “eat more, live longer.” In contrast, metformin-treated females were only ~67 % of the mass of controls. Our results suggest that hormetic agents like metformin may derive significant trade-offs with life extension, whereas health and longevity benefits may be obtained with less cost by agents like aspirin that regulate geroprotective pathways.

How does aspirin increase lifespan? It’s anti-inflammatory, but that just moves the question a step further back. It turns out that aspirin chelates iron, which could account for its anti-inflammatory property.(4)

These results may help to explain the interaction of nonsteroidal anti-inflammatory drugs with free radicals and the anti-inflammatory properties of these agents, inasmuch as accumulating evidence indicates that much of the injury observed during inflammatory disorders may be mediated by oxidative stress frequently induced by iron-dependent reactions.


It follows from this that control of iron may be the proximate mechanism of action of salicin, aspirin, and calorie restriction, or that control of iron operates through the same biochemical pathways to extend life. I discussed this at length in my new book, Dumping Iron.

Aspirin could be one of the most potent anti-aging drugs. We might see more research on it except for the fact that pharmaceutical companies can’t make big profits from it, as it’s dirt cheap and over-the-counter.

PS: See my book, Dumping Iron.

PS: Check out our Supplements Buying Guide for Men.

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  1. Tuba says:

    Metformin is a plant extract. Not for me, but neither is aspirin. I do chew willow twigs once a week because I teach about them.

  2. Asf says:

    So do you take it daily? If so, how much?

  3. kuih says:

    I am a 30 year old with persistently high platelets and c-reactive protein counts for years that no doctor has been able to find a cause for, and lately high ferritin too. I have no obvious symptoms besides chronic fatigue. There seems to be some sort of mysterious inflammatory process going on in my body, and I worry about what damage it’s doing to me over the long term. Now, I have read here and elsewhere that daily aspirin is normally contraindicated for people under 50. For someone in my situation, do you think starting a daily baby aspirin might outweigh the risk of bleeding?

    • P. D. Mangan says:

      Of course I can’t give medical advice. From what you’re telling me, a better line of attack might be to find out the cause of your symptoms and lab values. High platelets and high ferritin seem like things that a doctor could work on to find causes.

  4. J. says:

    I think the benefits of aspirin are mostly from salicylic acid. Aspirin has cox-2 inhibitory action and salicylic acid doesnt. The body rapidly metabolized aspirin-> salicylic acid.

    salicylic acid has it all

    – direct agonism of ampk means
    Mtor1 down so less protein synthesis
    Mtor1 down so more autophagy
    nfkb down less inflammation
    ampk mediated nfr2 upregulation, more endogenous anti-oxidants

    -iron chelation

    – hopefully ros mediated autophagy and nfr2 upregulation

  5. Ash says:

    Thousands of users have created longevity stacks by using metformin and aspirin, see their dosage and supplements here

  6. Rob H says:

    It’s also good to note from the study extract that the Passiflora tablets that help me sleep well at night can also extend longevity (at least in yeast). And also Apium graveolens = celery. So will try to add more of that to my diet. Good tips!!

    • P. D. Mangan says:

      I noticed that – I looked up most of the Latin names listed, figured it was grape seed or something, but, no – celery seed! BTW, also noteworthy was that extracts of tea (Camellia sinensis) and chocolate (Theobroma cacao) did not extend yeast lifespan.

  7. Rob H says:

    That’s interesting that those other two polyphenol-rich nutrients (cacao and tea extract) did not help extend yeast lifespan, but undoubtedly they have other health benefits..

    Re: aspirin, as well as reducing iron, there is definitely something to the salicylic acid too. You may remember I recommended those glycine posts to you recently, well in the 3rd one (see link below) Dr Brind talks about the benefits of salicylic acid:

    Talking of glycine, in another unrelated article I was reading on ways to improve sleep, it mentioned that the herbal teas that help improve sleep (ie chamonile, passiflora and valerian – ie the herbs mentioned in the above extract) do so via the mildly sedative effects of glycine. Not sure if that’s true or not, but glycine sure seems to be cropping up quite a lot in health studies recently!

    In terms of aspirin tablets, personally, I am still a little reticent to take them regularly (I guess when I get over 50 I may reconsider). I still have memories of visiting my Dad in hospital when I was a kid, when he had unwittingly caused internal bleeding from using a few too many aspirins! But, if you want to increase your intake of salicylic acid from food sources,
    then I came across this website which lists out foods in each category:

    Funnily enough, there is quite a high correlation with high polyphenol/ flavanoid containing foods (ie the top 100 polyphenol containing foods listed on the link which Joe O included in his recent guest post).

  8. I’m reading Dumping Iron. Pretty good. I’ve got to get my ferritin measured.

  9. Jim says:

    Any thoughts on taking children’s aspirin instead of adult aspirin? Any difference?

    • P. D. Mangan says:

      Jim, the only difference in children’s aspirin is the dose. Most studies on low-dose aspirin look at a daily 80 mg dose, which is the same as a children’s (baby) aspirin.

  10. Tom says:

    Pterostilbene should be also used against inflammation:

    It decrease tnf alpha a lot

  11. jt says:

    Any thoughts about avoiding the hearing loss side effect of long term salicylic acid use?

  12. Johnny says:


    Would it be a good advice to take 80mg aspirin 3 times a week as a fit 30 year old?



    • P. D. Mangan says:

      Hi Johnny, due to the potential of adverse side effects with aspirin, I always tell people they should check with their doctor before long-term aspirin use. The consensus of opinion in the medical world is that there’s a much better ratio of benefits to risks above the age of about 50.

  13. Christian E says:

    Hello Dennis. I purchased Dumping Iron. Thank you for leading me straight to the blood bank! Such compelling evidence of the benefits of blood donation. Could the reduction in blood viscosity via blood donation be additional variable – other than iron reduction – in contributing to positive health outcomes? see, for example this interesting research:

    For example, Ginkgo Biloba – as a longevity extender – is known as very effective in reducing blood viscosity.

    • P. D. Mangan says:

      Hi Christian, I can’t say I know a lot about blood viscosity. It seems to me that any changes in viscosity should be quite temporary, but I could be wrong on that.

      One thing that does interest me a lot, which is kind of similar, is fibrinogen, a blood clotting protein. Increases in fibrinogen increase risk for heart attack.

  14. Christian E says:

    and just came across this research showing Statin drugs reduce blood viscosity.
    I know there is also research out there showing that Statin uses reduces iron…

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