I am finishing a four-day fast today. In the hope of synergizing senolytic modalities, I took 2.5 g of quercetin last night and another 2.5 g this morning. I don’t take quercetin regularly, because studies in mice show that daily administration doesn’t lengthen lifespan, and may shorten it. But for the present, quercetin is the most readily-available senolytic agent we have.
It’s my speculation that fasting might prime senescent cells for elimination, in the same way that fasting has been shown to prime cancer cells for elimination by chemotherapy or radiation. Valter Longo has been at the center of the latter research, and he tells me that he is testing the senolytic hypothesis now, with no results yet.
Quercetin is a flavonol found in many vegetables and fruits, especially capers, radishes, cilantro and onions.
Quercetin by itself has been found to be only a weak senolytic in mice, and it has not yet been tested in humans. It is somewhat better when combined with dasatinib, but dasatinib is highly toxic and not something I would experiment with based on current knowledge.
People have asked about my fasting discipline. I answer that different people have vastly different experiences, and you won’t know until you try for yourself. I fast regularly one day a week, and when I take on a longer fast there is often a hump to get over on the second day, sometimes headaches and malaise. I use enema to clear the colon on the second day, and often this seems to help. I take caffeine daily while fasting, which is more than in my regular life.
The chief complaint I have after the second day is that I am too mellow, content to lie in bed. No restlessness during sitting meditation. Time slips by, and I feel no urgency about accomplishing anything. I read things I might not otherwise find time for. I go for long walks and entertain wide-ranging thoughts.
I have been doing intermittent fasting – skipping breakfast every day – for several months now and have noticed good effects on body composition.
I find the opposite. I have tons of energy. My HGH levels and Noradrenaline levels go way up with my metabolism. Once I’m burning fat for fuel, say second day of 4 day fast onward – I’m energized. I lift weights throughout .
this study states that fisetin (available otc) is a better senolytic https://www.ncbi.nlm.nih.gov/pubmed/28273655
Also, piperlongumine (not available otc, so long pepper on your food is another way, inefficient probably because of low dosage, but anyway, could not hurt).
And recently, I found that another flavonoid, apigenin reduces SASP, like rapamycin.
By reading this paper on Rapamycin targeting not only nrf2 pathway (which is probably not related to its senolytic capability), but also reducing SASP, I found the apigenin study above.
So now my senolytic stack is fisetin + apigenin, and long pepper on food.
Thanks Angus, good information. Seems to me that some people may have accidentally created senolytic diets in pre-tech times… you can get a lot of quercetin from capers, now if that were synergistic with flavanoids like fisetin…
Hi I was wondering what was your protocol for the Fisetin + Apigenin combo? What doses are you taking for senolytic effect? Thanks so much!
4 days is my next goal. My first and only fast was a full 3 days and my experience was similar to yours – a complete change in operating harmonic – like a full octave lower. Time seems to slow down for me and I find attempted efforts at maintaining operating in the present world challenging; driving at highway speeds seemed insanely fast and pure madness. Conversations with co-workers can also be challenging due to my slowed tempo….I listen better and truly contemplate their words as my usual tendency of formulating responses in near real-time is absent however I can sense their impatience (tech breeds impatience). I find interaction with computers (the base of my work) to be unpleasant. Despite being mildly obsessed with extracting the perfect espresso shot my body rejects caffeine during fasting. Indeed breaking of my fast wasn’t a good experience as I was of course ignorant of a more healthy approach to what I label “caloric re-entry”.
Every body different I suppose….
Curious if you are pushing for 5 days as Dr. Longo’s research seems to indicate maximum benefit at 5?
Thank you for sharing.
Josh, many thanks for this and all your other posts a. does not caffeine inhibit autophagy? b. it seems to me I read that quercetin, when taken orally, breaks down very quickly to compounds that are either not effective or may be even slightly countereffective?
Here’s an article that says caffeine inhibits autophagy:
Here’s an article that says caffeine enhances autophagy:
Wow, I love biology… I mean, how can I not, since it agrees with every possible belief I could have (as long as I ignore the countering papers) 😉
“up-to-date findings on how autophagy is executed and regulated at the molecular level and how its disruption can lead to disease.” is it worth trying with this risc?
I find myself feeling a bit tired and washed out on the third day of my five day fasts, but after that I’m fine. I’ve been snowboarding on day four, and felt fine.
Has anyone considered the pros/cons of taking Enzymatically Modified Isoquercetin (EMIQ) instead of plain quercetin?
It’s supposed to be considerably more bio-available, but I think every study I have seen that studied quercetin as a senolytic just used plain old quercetin, so we don’t have any data per se on it.
Isoquercetin is exactly the same mechanistically it only differs slightly in chemical structure and is signficantly better bioavailability. See here:
Rapamycin lowers production of SASP factors and decreases production of senescent cells.
Last July on Rapamycin Redox I first reported extraordinary success with rapamycin formula and said would open medical office to provide such treatment if success continued for 1 year.
Now have opened such medical office. Visit website: rapamycintherapy.com.
Alan Green, M.D.
I am interested but the address is not working.
What do you think about rutin? I suppose that it more bio-available and more preferable, than quercetin. I take 500 mg of rutin 5 days in a row and before that I take apple pectin during 5-7 days in a row (1400 mg twice a day) to make bio-available of rutin more better. But I didn’t never take rutin during my fasting (I also practice 5 days of fasting every month.) Maybe it will be more preferable to take 2.5 g of rutin in the penultimate and last days of fasting, and therefore intake of apple pectin do not necessary / unnecessary.
Is rutin a senolytic? Perhaps it is but I haven’t seen that conclusion anywhere.
It is related to Quercetin being a close chemical cousin. It is also one step more distant in the NAD scavenging chain.
HI there just check out the chemical structure and rutin actuaklly contains a molecule of quercetin attached to a sugar back bone (rutinoside)
in fact rutin has another name I think
How hard would it be to study if fasting does clear Senescent Cells? If it does as you and many suspect, it’s a problem for Big Pharma….There’s tons of free info online, and it’s true that each person should experiment to see their individual response to fasting. But what’s to sell? I love it, and do it and am here to say that once you learn what to expect, it can be cathartic, healthy and something that can easily be incorporated in to anyone’s lifestyle. Lets have more on this please, isn’t the idea of people healing themselves, and maybe extending healthspans “delicious”?
Josh, how about interviewing one of these centenarians about their fasting (and other) habits ?
Oops, I wanted to provide links but was not able to. Just search for 105 year old doctor in UK. He is in great shape and still practices medicine ! His name is Bill Frankland. Another one is a 105 year old Robert Marchand, a frenchman who recently broke record in cycling.
I’ve only met one person with 103, she was my wife’s grandmother. At eighty she was traveling a lot and with great shape. My wife remenbers her always fat, never fasting and of course no sport. As well, her grand-mother lived up to 105. So, looks like, at least in this case, genes are more important than lifestyle for this type of longevity.
I’d like to add as well, that other younger people (about 80’s) that I’ve met with outstanding looks/health/activity don’t do any kind of fasting, sport and eat what they like.
Yes – after age 90, genes are more important than life style, and after age 100, it’s genes all the way.
There was some research done a while back on the enhanced longevity of active Seventh Day Adventists and LDS (Mormon) high priests. These two groups’ were thought to live longer due to adherence to their religious health codes – e.g. not smoking, little or no alcohol , reduced meat consumption, regular exercise, etc. One of the common elements of their health code that is often overlooked is fasting. Seventh Day Adventists are encouraged to fast four times a year, and the first Sunday of each month LDS congregations observe a 24-hour fast from both food and water. I wonder if fasting might play an unrecognized, yet prominent, role in their enhanced longevity? Could the stress of periodic fasting clear some types of senescent cells?
Hey don i know its been a while since you made this comment but can you expand at all on the Seventh Day Adventist’s fasting 4 times a year. How long do they fast for at these tines?
Do you have any references for this? It would be really great if you did
It’s the opposite, Josh. : (
At least with the mechanism used by current senolytics.
“MM on April 8, 2017 at 12:28 am
It’s the opposite, Josh. : (
At least with the mechanism used by current senolytics.”
Any references for why human fasting (short or prolonged, water-only or whatever FMD) would not be synergistic with senescent cell clearance experimentation (like D+Q)?
Is this a routine that you plan to repeat periodically?
There is a study in mice that shows that 1 per month dosing of quercetin + dasatinib improved cardiovascular markers in mice.
Isn’t there scientific proof that fasting triggers apoptosis and autophagy? If so, isn’t that senolytic?
Intermittent fasting may be the best thing that I have ever done, paired perhaps with ketogenic diet.
Some related info
there was a study I remeber reading about done sometime in the 1940’s where they fed rodents every other day , They lived almost as long as calorically restricted mice and were larger than the controls
I saw the study in Roy Walfords book ttiled How to live to 120 or something like that if you want to track it down
I jsut got done with an 11 day fast, lost 12 pounds actually to reduce taste boredom make big feasts of almost 0 calorie food my favorite is microwaved vegetables with very low calories like broccoli cauliflower mushrooms ginger celery onion kale tiny tomoatoes tmumeric sliced etc mixed in a broth made form vegetable bullion you can make a huge meal with almost 100 calories
other snacks microwaved mushrooms and mustard
occasional plan popcorn cooked in a microwave in a bowl with a paper plate covering the top wuith rubber bands
and diet chocolate fudge soda rom time to time!!! I fyou maek fasting fun it is easier to do
The first 3 days I just plan on being sick by day 5 everything was fine by day 7 no hunger at all plenty of energy! Stays the same thrpough day 11!
Oh I forgot to add my biggest fasting secret of all>>>
Eati g canned hearts of palm whenever you are hungry or stomach growls
it seems like it is real food but has almost no calories
But then there are the bad effects of fasting… oops, not so much. Darn you guys and your snack-stealing “evidence”!
Hi Josh, do you think part of the contradiction with respect to effects of quercetin could be related to the presence of Vitamin C?
The effect of quercetin supplementation on selected markers of inflammation and oxidative stress, 2012
This article suggests that without the presence of glutathion (GSH) or ascorbate, toxic products are created from quinone.
Also I mean to add…
The idea that fasting or caloric restriction would enhance senolytic modalities is interesting.
In this study they found that the organ weight significantly declined due to a fasting mimicking diet. There was a commentary piece done on that study somewhere which raised the possibility that it could be that the immune system was activated to increase the rate at which it could eliminate senescent cells by the fasting. I can’t recall where that was though.
I would like to know why you selected 2.5 grams x 2 of quercetin, and what brand and form of quercetin did you use?
We’re flying blind. There is no data for humans. We don’t even know if quercetin works without dasatinib. I just picked what seemed a jumbo dose for one-time goosing. I used the name brand of my local food coop.
Just wondering how often you repeat the 2.5 X 2 grams of quercetin? Once a week, once a month?
once or twice a year
Thanks for your reply. Does that mean you only fast once or twice a year also?
was there any noticeable outcome of your Quercetin intake? Did you repeat the routine?
Just trying to do the same after fasting.
Hey all I was taking 2.5 grams quercetin and 2.5 grams rutin in the morning and at night for a cojuple of weeks
one ting I noticed is that I started feeling like I was just recovering from the flu
loss of endurance in my muscles like when walking up stairs loss of energy
also I noticed my luings felt a little raw and I was coughing a bit
I am wondering if this is the result of various cells being killed off and not yet replaced??
I noticed fisiten is very closely related to rutin and quercetin and has been found to be effective at killing off cacner cells in combo wigth melatonin
Any thoughts about the results of the study “Investigation of quercetin and hyperoside as senolytics in adult human endothelial cells” published in PLOS One?
From the abstract: “… Thus, in primary adult human endothelial cells, quercetin and Q3G are not senolytics. Earlier work reporting positive results was done with HUVECs, and given their origin and the disparate findings from the current study, these may not be the best cells for evaluating potential senolytics in clinically relevant endothelial cells.”
Note that there is another study indicating that some senolytics work on some types of cells but not others:
“New agents that target senescent cells: the flavone, fisetin, and the BCL-XL inhibitors, A1331852 and A1155463” .
Considering Quercetin, the problem is that it is very often used in combination with dasatinib, and there is rarely a control with just Quercetin.
I still found this study that used Quercetin by itself and showed an effect on age dependent markers in presence of hyperglycemia (Kidney cells):
“Short-term High Dose of Quercetin and Resveratrol Alters Aging Markers in Human Kidney Cells”
If you know of other studies with Quercetin alone on various type of cells, please share !
Into the 88th hour of my water/electrolyte only fast and wondering about this myself. The only thing I’ve been taking otherwise is EGCG, very minute amounts of cocoa in my coffee and ALCAR. All these are known to enhance or induce autophagy and the last helps with lipid transport as well (ketosis).
Any news on fasting as a synolitic since this was posted?
I also heard high dose Rutin and quercetinc are ….senolytic…and lef.org for some reason thinks tocotrienols (a form of vit e they sell) is also senolytic
As to the question regarding – Should I take supplements during fasting, I think the answer may be – not if they are encased in a gelatin capsule.
Even a very small amount of amino acid, especially Lysine, turns off Autophagy.
Gelatin contains the amino acids lysine, alanine, and arginine.
Can you point to any research paper confirming that amino acid turns of autophagy?
When fasting for a week I supplement with creatine and BCAA (L-Leucine, L-Valine, L-Isoleucine) to minimize loss of muscles.
I take both supplements when going to the gym 5 times a week.
Leucine intake works against the effectiveness of fasting. Lowing Leucine intake alone is believed to be as effect as fasting calorie restriction. I believe this is why Longo’s fasting mimicking diet plans are vegan. Leucine is mainly found in meats, eggs, dairy, and apparently your muscle supplement. Better to skip the protein supplements and stick to cardio and avoid muscle breakdown workouts during fasting. https://nutritionfacts.org/2015/06/16/living-longer-by-reducing-leucine-intake/
It’s now October 20, 2018. Last week a strong study came out showing that Fisetin is the most potent senolytic discovered yet. Even Fight Aging was impressed. I’m going to pose the same questions here
FA says “. Consider a combination of fisetin, dasatinib, quercetin, piperlongumine, and FOXO4-DRI – multiple different mechanisms to provoke apoptosis that are all hitting senescent cells at the same time” The study being conducted on humans will use 20mg/kg of Fisetin for two days.
Opinions needed! for a two-day zombie cell clearing:
Would this 2 day cleaning be more effective if taken while fasting?
How long to fast before taking?
Should fisetin be consumed on an empty stomach or with food.
Take all 1200 mg at once or in divided doses each day?
Should capsules be taken whole or dumped out and mixed with some type of oil? I’m guessing dumped if fasting due to gelatin.
Should piperlongumine be taken at same time or later in day?
How much piperlongumine to go with 1200 mg of Fisetin?
How much Quercetin to take at same time or later as well?
Stop all other supplements those two days?
Should we try to get FOXO4-DRI as well (hard to do)?
My wife and I take 100mg of Fisetin & 1000mg of Curcumin with Bioperine twice a day while doing our 5 day vegan fasting mimics which is basically a lower carb and lower calorie version of Longo’s FMD. I feel till there is more information about the safety of high fisetin dosages low balling it seems wise.
Fasting makes more sense to me immediately after senescent cells clearance as a means to increase the efficiency of the treatment.
I regularly fast for 3 days. Now, based on the latest scientific findings I’m going to do a self experiment on senescent clearance in the next fasting cycle, as follows:
Day 1 – 1.5g Fisetin + 500mg Trans-ferulic acid
Day 2 – 1.5g Fisetin + 500mg Trans-ferulic acid
Day 3 – 1g Azithromycin
Day 4 – 1g Azithromycin, Fasting day I
Day 5 – Fasting day II
Day 6 – Fasting day III