Is fasting senolytic?

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.

30 thoughts on “Is fasting senolytic?

  1. I have been doing intermittent fasting – skipping breakfast every day – for several months now and have noticed good effects on body composition.

  2. 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 .

  3. Hi,

    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.
    https://www.ncbi.nlm.nih.gov/pubmed/28378188

    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.
    cf. http://oregonstate.edu/ua/ncs/archives/2017/apr/new-function-discovered-compound-may-help-slow-aging

    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…

  4. 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.

  5. 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?

  6. 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.

  7. 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.

  8. 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.

  9. Hello, Josh
    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.

  10. 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”?

  11. 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.

      Best.

  12. 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?

  13. Quoting:

    “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)?

  14. 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.

  15. Hello All

    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!

  16. 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

Leave a Reply

Your email address will not be published. Required fields are marked *