OTC Supplement Quercetin Kills Senescent Cells

 

SENS

Aubrey de Grey, the theorist of anti-aging science, came up with so-called Strategies for Engineered Negligible Senescence (SENS), which would have the ability to repair physiological damage and therefore allow for a “negligible” rate of aging. Most of the seven items on the list of aging problems we are nowhere near to solving. Right now, the enhancement of autophagy through fasting, exercise, and various chemical means looks like the best anti-aging method going, in my opinion, but that still doesn’t really halt cellular and tissue damage.

One of the items on the SENS list is dealing with senescent cells, which are cells that have passed their “sell by” date. They have ceased to grow and divide, but they still produce inflammatory cytokines, and are considered to be a major cause of age-related disease and dysfunction.

Senolytics

Now, a group of scientists has discovered a successful way to deal with senescent cells: The Achilles’ Heel of Senescent Cells: From Transcriptome to Senolytic Drugs. From the abstract:

The healthspan of mice is enhanced by killing senescent cells using a transgenic suicide gene. Achieving the same using small molecules would have a tremendous impact on quality of life and burden of age-related chronic diseases. Here, we describe the rationale for identification and validation of a new class of drugs termed senolytics, which selectively kill senescent cells. By transcript analysis, we discovered increased expression of pro-survival networks in senescent cells… Drugs targeting these factors selectively killed senescent cells. Dasatinib eliminated senescent human fat cell progenitors, while quercetin was more effective against senescent human endothelial cells and mouse BM-MSCs. The combination of dasatinib and quercetin was effective in eliminating senescent MEFs… In old mice, cardiac function and carotid vascular reactivity were improved 5 days after a single dose. Following irradiation of one limb in mice, a single dose led to improved exercise capacity for at least 7 months following drug treatment. … These results demonstrate the feasibility of selectively ablating senescent cells and the efficacy of senolytics for alleviating symptoms of frailty and extending healthspan.

The two compounds used were dasatinib, an anti-cancer drug, and quercetin, a phytochemical that is available as an over-the-counter supplement. While the combination of both dasatinib and quercetin was the most effective, quercetin alone was more effective than dasatinib alone against senescent epithelial cells. The dose of quercetin used was 50mg/kg body weight. (From the full paper in PDF.)  Dose needs to be divided by 12 for mouse/human interconversion, so more like 300 mg for a 70 kg man.

One dose of the combined treatment improved cardiac function in old mice after 5 days.

Dasatinib is a prescription drug, but quercetin is readily available and inexpensive. A recent review paper on quercetin states that “a regular diet provides amounts of quercetin (10 μM) by supplementation with quercetin-enriched foods or supplements.”

The first paper states that in the in vitro part of the experiment, the concentration of quercetin used was in fact 10 μM. So we’re in luck: supplementation will get us into that range.

The authors also state that getting rid of as few as 30% of senescent cells will result in a huge improvement in health. The authors of the study are quite enthusiastic about it, referring to their compounds as “senolytics”:

“We view this study as a big, first step toward developing treatments that can be given safely to patients to extend healthspan or to treat age-related diseases and disorders,” said TSRI Professor Paul Robbins, PhD, who with Associate Professor Laura Niedernhofer, MD, PhD, led the research efforts for the paper at Scripps Florida. “When senolytic agents, like the combination we identified, are used clinically, the results could be transformative.”

“The prototypes of these senolytic agents have more than proven their ability to alleviate multiple characteristics associated with aging,” said Mayo Clinic Professor James Kirkland, MD, PhD, senior author of the new study. “It may eventually become feasible to delay, prevent, alleviate or even reverse multiple chronic diseases and disabilities as a group, instead of just one at a time.”

I’m tempted to try some quercetin, a supplement I’ve never taken.

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35 comments
Allan Folz says March 12, 2015

I’m tempted for you to try some quercetin too. 🙂

The problem I have with so many of these supplements though, is 1) how do you know its working 2) how do you know its not creating any new and worse problems.

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Stephen Werner says March 12, 2015

At ~240 lbs, I would need over 7 grams/dose.

I had previously tried Quercetin due to it’s claimed ability to enhance endurance, both as FRS brand energy drinks (about 1 gram quercetin ea., if I recall correctly) and in capsule form. The FRS drinks tasted terrible to my palate, so I switched to Solray 500 mg capsules to test. I could perceive no difference with/without, so I have a half bottle on a shelf.

I was reluctant to take 14 capsules, so I tried 3 (1500 mg) this evening. Now, I have an upset stomach (I don’t recall ever having this with the FRS drinks nor single 500 capsule doses).

I don’t have a cast-iron stomach, by any means, so my experience may not be typical. Still, it might be wise to start at a reduced dosage to start.

Given the indicated dosage, I checked Powder City for bulk powder – they are currently sold out. You other Rogue readers must have beaten me to their stock.

Yet, if I’m correct that it was the quercetin that gave FRS a strong bitter after-taste, I’m not sure what I could add to help choke down 7 grams at a shot. Any ideas?

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    Sam says March 13, 2015

    You can buy gelatin capsules and fillers reasonably cheap.

    Reply
      Stephen Werner says March 13, 2015

      I actually have one of those THE Capsule Machine capsule filling devices, which I could well use, as you suggest.

      It would still be a lot of caspsule – even if I cannot read correctly (for some reason, I got the idea in my head that Mangan had written “3.5 grams for a 50 kg man”. Apparently I could use info on supplement s for my eye site, or short-term memory…)

      Actually, 5.4 grams would be my target – so only 11 500mg capsules; which given my initial response to 3, I’d break out into sub-doses throughout the day.

      I guess what I should really do is read the whole study to see if lower doses were tried, and 50 mg/kg was found to be optimal; or, if it was just a dosage chosen aimed at being sure a response would be seen in the rats.

      Perhaps benefits could be had at only a couple of grams/day?

      Reply
    Stephen Werner says March 13, 2015

    Well, that was quick. Last night, they were out. Today, I get notification that they have it back in stock:

    Product is back in stock!
    You subscribed to this product:

    Product image
    Quercetin Dihydrate Powder
    100 Grams

    In Stock: 500.

    Current product price: 24.26.

    Subscription was created: Today, 01:20.

    Hello!

    Earlier you have subscribed to the product, because it was out of stock. We are glad to inform you that it is back in stock now. So you can buy it.

    Wish you good purchases!

    Powder City administration

    —————————

    If anyone else is interested, http://www.powdercity.com/products/quercetin-dihydrate-powder

    Reply
Sam says March 13, 2015

If this works out to be true it would seem to be a huge breakthrough. I have some 500mg quercetin. I bought it for inflammation. I’m unfortunately bad about buying stuff and not trying it for long periods. I’ll try two 500mg capsules and then up it.

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Sam says March 13, 2015

I went and looked at a file I saved about quercetin. In Wikipedia there was an entry. “…A study in the British Journal of Cancer showed that when treated with a combination of quercetin and ultrasound at 20 KHz for 1 minute duration, skin and prostate cancers show a 90% mortality within 48 hours with no visible mortality of normal cells…”

It’s not in the present quercetin wiki article online. The paper was,

“(2005) “Induction of cancer-specific cytotoxicity towards human prostate and skin cells using quercetin and ultrasound”. British Journal of Cancer 92″

Now I’m going to get a little off track. I read a vast amount of stuff and sometimes make connections. Sometimes these may be like seeing elephants in clouds. Sometimes not. The above paper says”ultrasound”. Ultrasound what’s that about? I think I know. There’s a Prof. Gerald H. Pollack, , PhD that has found a fourth state of water. Yes the Prof. knows about polywater so he was real careful with his studies and has been at this for a number of years to verify them. It seems that some Hydrophilic materials order water molecules in a crystalline manner for extremely long distances. In some cases as much as a half a millimeter. Cell material, certain plastics, gelatin gels, etc. He found that a “Exclusion Zone” was created. A negative charged area that became crystalline ordered and pushed out contaminants. Like ice crystals push out dirt. This also explains the negative charge around cells. So how does this tie in? Maybe the ultrasound is vibrating the “exclusion Zone” so that it breaks up the crystalline area and the quercetin can reach the cell. Here’s a video of his research. I think this will become important stuff as it’s researched further. I also bet it will take a while as the whole subject is contaminated with pseudo (or maybe not) trap, magnetic, energized, etc. water stuff. He also has a TED talk video.

https://www.youtube.com/watch?v=XVBEwn6iWOo

This whole electrical potential of cells I believe is super important. Normal cells are a little negative. Cancer cells are strongly negative. There’s a doctor who cured some cancers by introducing an electrode into cancer tumors and reversing the strong electrostatic field of the cancer cell. He says cancer interrupts the electromagnetic??? flow??? in the body.

Dr. Bjorn Nordenstrom – Biology, Electricity, and Cancer

http://www.rexresearch.com/nordenstrom/nordenstrom.htm

It could be that the whole qi (氣), “energy force” in Chinese culture has a scientific basis we just don’t know how to activate, control or recognize when it’s out of balance.

Reply
Stephen Werner says March 16, 2015

http://www.sciencedirect.com/science/article/pii/S0531556510002196

Anti-ageing and rejuvenating effects of quercetin
Niki Chondrogiannia, Suzanne Kapetaa, Ioanna Chinoub, Katerina Vassilatouc, Issidora Papassiderid, Efstathios S. Gonosa
Experimental Gerontology
Volume 45, Issue 10, October 2010

Extract from abstract:

“Several natural compounds possess anti-ageing/anti-oxidant properties. In this study, we have identified quercetin (QUER) and its derivative, namely quercetin caprylate (QU-CAP) as a proteasome activator with anti-oxidant properties that consequently influence cellular lifespan, survival and viability of HFL-1 primary human fibroblasts. Moreover, when these compounds are supplemented to already senescent fibroblasts, a rejuvenating effect is observed. “

Reply
ProudDaddy says April 3, 2015

Shouldn’t you be calculating the human equivalent dosage which would be about 1/12th of the dosage you used?

Reply
    P. D. Mangan says April 3, 2015

    Possibly. The dose that the review states is effective is 10 micromolar, and this is the dose used in killing senescent cells. I think that in humans this same level will be achieved, but probably the half-life will be longer. There’s actually some controversy about whether human equivalent doses should be used.

    Reply
Sam says April 4, 2015

I tried this and it didn’t kill me. Started 1 gram. Next day 2 grams. Next day 4 grams. 4 capsules in morning empty stomach. 4 capsules after eating. It made me a little anxious but that means nothing I have anxiety problems so it could be just me. I felt better when doing this. Seemed a little more clear headed. Possible vision improvement. Could all be in my head though.

dose

180 lbs = 82 kg

50mg/kg

50mg/kg * 82 kg = 4100 mg

4100 mg/500mg per capsules = 8.2 capsules

Supposedly last 7 months???? I’m not seeing it maybe I read something wrong. Maybe it would take more over a longer period of time for a human being larger. I’ll try it again but I don’t want to over do it.

Reply
Martin says April 8, 2015

To convert from animal dosages to human dosages you must adjust for the size. Given the difference in metabolism rates and the surface area of a human vs. a mouse, you only need 3/37 of the dosage per kg. So 50 mg/kg in a mouse is equal to 400 mg for a 100kg (220 pound) person.

http://suppversity.blogspot.com/2011/06/ask-dr-andro-what-are-human-equivalen.html

Reply
    ProudDaddy says April 8, 2015

    Per my previous comment, we are using the same reference (Suppversity). I’ve checked medical journal articles, and they have the same numbers. Even published studies often make the mistake of using a straight mg/kg conversion. It is extremely important in this case because the human dosage becomes both affordable and a common single pill dose.

    Reply
Herman Rutner says August 20, 2015

As a chemist, I have worked with liposomes or microemulsions as efficient delivery systems for insoluble drugs like turmeric with low bioavailability due to low solubility. Many liposomal supplement formulations are sold commercially, possibly even quercetin. You could easily make a microemulsion of quercetin powder mixed with some water, olive oil and a few drops of liquid lecithin to solubilize quercitin by blending in a coffee mill grinder. Or you could add quercetin as a water paste to a commercial microemulsion, mayonaise and mix well. Liposomal delivery may increase uptake by as much as 10 fold and you could use as little as 100 mg quercetin instead of 1000mg.

Reply
    P. D. Mangan says August 20, 2015

    Mr. Rutner, fascinating comment. I wonder if you could elaborate. How is making an emulsion like you describe different from a liposome, or are they the same? My understanding was that a liposome somehow contained the substance to be delivered *inside* a fat globule, whereas what you describe merely involves mixing, as far as I can see. But maybe I’m wrong about the liposome.

    Reply
Eugene D. Weinberg on Iron Toxicity - Rogue Health and Fitness says November 12, 2015

[…] study showed that quercetin, which is a strong iron chelator, kills some senescent cells. (See my post on quercetin and how it kills senescent cells.) Might there be an iron […]

Reply
Peter Morgans says January 3, 2016

All these comments lol but not one post stating experienced benefits.

Can anyone say it works?

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    P. D. Mangan says January 4, 2016

    I personally have never taken quercetin, though I should probably get off my backside and try it. In the study they used quercetin + dasanatib, a cancer drug.

    Reply
Allan Silliphant says January 26, 2016

Hi, P.D., As yo may know by now, I’m a huge fan of your work, site, & insight. I may
have mentioned this before, but I have been using metformin for over 18 years as
a VA patient in the system. I had nasty G.I. issues & about 6 years ago got my VA
(PC) internist , to switch me over the EXTENDED RELEASE VERSION. I was able to go from 500mg twice a day up to 1500mg & recently a full 2000mg. When I went up on the dosage of metformin, I got permission to reduce the dangerous & nasty pancreas stimulant, GLIPIZIDE down to 5mg taken only 5 times per week. I have given an account on your site that, I’m an activist for better, safer, more effective medical care, for my fellow vets. So, since we are all on metformin
anyway, being T2 diabetes patients, we resolved, within our informal circle to
cut back on the stuff like GLIPIZIDE, with consultation & consent of our docs.
Over the last year this has evolved into an informal research effort, trying various
non prescription substances, to improve the results. As I’ve stated recently on
your forum, My changes for the better over the last 130 days have been trans-formative . We take fasting finger-stick samplings. All of us are doing way better,
but in my case, I have been continuing to fast for up to 4 hours more…after a
finger-stick, & try to lose weight by staying on a 1500 – 1600 calorie daily diet.
I use a super accurate digital scale. My starting weight was 219 lbs. 130 days
ago, today I hit a pre-breakfast low of just 180. I do a reasonable amount of
light hand weight work, take a mile walk, and do 300 reps of high knee lifts,
as my coronary arteries , need some help from healthy legs. In April, this year
the surgical team at VA/UCLA Geffen is supposed to clear my left pair of occluded carotid arteries, like they did in 2013 on the right size. Our group just
started on testing quercetin, but we have hopes it will work with our senescent
cell build up. The reseveratrol we take is supposedly helped in terms of better
bio-availability by quercetin, the synthetic stilbene Ptero-pure, has worked
to drop down the HbA1C values to normal, from 7.9 in my case. Frankly, these
are far, far better results than the routine diabetes results, that keep patients
obese, & uninformed about the progress being made by non-pharma effective
agents. Your heart goes out to these vets with the swollen ankles, amputations,
blindness, predictable terminal diabetic illness. I just wish, your site, with the
options of physical workout, fasting & CR, & interest in the emerging body of
effective complementary natural agents were reaching them or their doctors.
I can’t speak yet about quercetin, but all the rest, including everything you favor,
seem to help, when compared to obsolete ” pharma only” treatment.

Reply
charles grashow says February 7, 2016

Have you seen this for Life Extension

http://www.lifeextension.com/magazine/2015/ss/sweep-away-senile-cells/page-01

A true life-extending supplement regimen should include regular quercetin doses of 150 to over 500 mg per day. A dose of 150 mg may be sufficient for most people. One strategy might involve taking the higher dose range of quercetin (over 500 mg per day) for several months and then dropping back to a maintenance dose of 150 mg each day.

Reply
    P. D. Mangan says February 7, 2016

    Thanks for that, Charles. I read a long thread recently at Longecity about people trying to figure out the best way to use quercetin for targeting senescent cells. Some were even trying to get a hold of dasatinib.

    PS: I read the full article, quite good. I’ve much to learn from that writing style too, great for the intelligent general reader to explain science.

    I don’t know why some polyphenols may be better than others. Those in black tea seem to have the strongest effect. But for instance taking curcumin, quercetin, EGCG, resveratrol at the same time may be overkill. What I’d like to know is which one is best.

    Reply
P. D. Mangan says April 16, 2016

“Crispy B” was unable to leave a comment, so he mailed it to me.

“Some more data, in the past when I was bothered by hay fever symptoms, sneezing, itchy eyes etc I would take Quercetin (from the health food store owners advice) to lower the symptoms and it worked. Both for me and a friend who also used it. The next year it worked again, and the next, now I don’t even have hay fever symptoms. Doubt it is because of Quercetin, but who knows.”

Reply
Iron Shortens Telomeres and Damages DNA - Rogue Health and Fitness says April 17, 2016

[…] P. D. Mangan on The Common Supplement Quercetin Kills Senescent Cells […]

Reply
How to make cheap anti-aging supplements - Rogue Health and Fitness says June 23, 2016

[…] blend of resveratrol (at 100 mg per capsule), unknown quantities of inositol hexaphosphate (IP6), quercetin, chlorogenic acid, green tea extract, and […]

Reply
Allan Silliphant ( VA medical patient/reseach activist) says December 17, 2016

An update, with some encouraging first person news. My general health improved so much in the last 18 months that the VA doctors have allowed to to have (20 days ago) the left side carotid-edarterectomy
surgery. The right side had been cleared in 2013, & remains clear. So to now is the left carotid pair. In order
to control 19 years of type2 diabetes, I had to lose 49 lbs. I did that in only 5 months, then kept it off for
more than a year, once I beat the excess weight. My body mass index is now about 18.4. I owe it to taking
extended release metformin, along with some very promising nutritional sups. They are: Ptero-pure, which
was developed by the USDA scientists, & human tested at U.of MS. pharma lab, at their Oxford MS campus.
It was found both safe & provided a benign reduction in blood pressure values. It is similar to resveratrol but
much longer( 4 times longer half-life in the blood stream). NR (niagen) precursor to NAD+, which seems to
improve the gene expression in the pathways between mitochondria & nuclear DNA. The issue of senescent
non-reproducing cells, to be eliminated by the bio process of apoptosis, influenced by quercetin & tocotrienols (one of the E vitamin sub groups). By the body eliminating these toxic, place-holding, morimund
cells, healthy new ones are grown. (much like culling a herd of grazing animals). My little group of Vet
activists have been beating down our diabetes, losing wieght, & getting healthier. I is a big deal to clear
nearly blocked carotids…Amazingly…I ca even see better with the 15 fold increase in left side blood flow to my eyes, face, and left brain hemisphere. I’ve been curling a 9 lb. weight 800 reps daily, and today begun to
restart on the right arm. Next week I’ll start the curls on the left arm, and work up to my prior activity. This
is real world endothelial repair, along with gene expression improvement , some fasting, & the great value
of regular workouts! We hope to get our VA doctors, & the Congressional oversight sub-committee to
take note, & consider this for our VA brothers losing sight, limbs & life in the existing program’s limited scope.

Reply
Mike Pietrich says January 11, 2017

I think the quercetin study in mice might be a bit optimistic to assume the same senolytic effect will happen in humans.

Mice have a lower BER than humans. BER correlates positively with lifespan.
Since the mice have a lower BER capacity it should be easier to achieve apoptosis than in humans.

The senolytic effect that happened in mice will be blunted by BER in human senescent cells.

Reply
    P. D. Mangan says January 11, 2017

    What’s BER?

    Reply
Paul Einar Sandvik says October 17, 2017

I wonder about if I can take the quercetin powder out of the gelatin capsules – directly in the mouth.I really do not like to swallow gelatin.
Thanks Paul Einar Sandvik

Reply
    P. D. Mangan says October 18, 2017

    Paul – I don’t see why not.

    Reply
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