LONGECITY

One of my goals is to live beyond the years of 200. I feel this goal is quite realistic even with our currently available methods. Aging is certainly very multifactorial and has to be targeted from multiple angles.

 

Here I want to share with you my personal fasting regimen for longevity.

 

I think longer fasts are incredibly healthy (and they might even be the next health revolution). The temporary uncomfortableness is nothing compared to the metabolic, health, and longevity benefits it gives us. Firstly, longer fasts (36h +) are a powerful driver of fat adaptation and thus promote metabolic flexibility. Secondly, next to being great for metabolic health (e.g. fat-adaptation, autophagy, stem cell activation) fasting also has powerful psychological benefits (e.g. developing self-discipline, opting for the hard things which makes me proud of myself).

 

Therefore I do a 5-day fasting-mimicking diet (FMD) four times per year. I do this to foster self-discipline, activate autophagy, tune-up my metabolic flexibility by having gene expression induced towards a more fat-adapted state, to cycle IGF-1 levels, and to clean out senescent cells.

• For fostering self-discipline I simply do not eat.

• For “boosting” autophagy I take an additional 8mg of rapamycin 1 day before starting the fast. For more info on why I take rapamycin, how I take it, and its benefits, see the article linked below.

• For why I cycle my IGF-1 levels, how that activates stem cell proliferation, and how that gives me the best of both worlds, read the respective Section here: How To Replace Growth Hormone.

• For cleaning out senescent cells: After day 3, nutrients and growth factors (e.g. insulin, IGF-1) are low, autophagy is ramped up, and mTOR is mostly inhibited (both from the fasting + the rapamycin). At this point, cells are highly sensitive. Therefore, I take a cocktail of senolytic drugs on days 3, 4, 5, and 6 -hoping to induce a body-wide clearance of senescent cells (which is much more effective in an mTOR-inhibited state). My senolytic regimen is comprised of the tyrosine kinase inhibitor dasatinib (2x 70mg/d) + the flavonoid quercetin (500mg 3x/d) + the antibiotic azithromycin (125mg/d). The most potent of these senolytics is certainly dasatinib. My guess is that over 90% of the senolytic effects are coming from dasatinib, while perhaps 10% or less are coming from the combined use of quercetin + azithromycin. I am aware that dasatinib does target certain cell types more than others (e.g. adipocytes > fibroblasts) while leaving some tissues quite untouched, but, unfortunately, no other senolytic agent is clinically tested and most of them are only available in a research setting (e.g. MDM2-inhibitors, Bcl2-inhibitors).

• In addition, I also take 1800mg/d of extended-release potassium tablets, 600mg elemental magnesium, 200mg calcium, and salt.

• I also take some supplements. For my exact supplement protocol, see here: Supplements Everyone Should Take.

While all this might sound extreme, I have performed this protocol quite a few times - without any (significant) adverse effects other than transient thrombocytopenia and a few mouth ulcers.

 

I do not fast for longer than 5 days because with the use of rapamycin and in my already fat-adapted state, my metabolic state is likely already at a “day-3-level” on day 1. Furthermore, I do not compromise my peripheral thyroid sensitivity too much. I opt to do a fasting-mimicking “fast” instead of a complete fast because I am already quite low in body-fat, and the fatty acids my cells need to use for energy have to come from somewhere.

 

I usually consume around 800kcal/d of nut butters (coconut, peanut, hazelnut). Nut butters have negligible glycemic and insulin indices, essentially keeping my insulin levels unchanged. The main benefits of fasting (perhaps 80% or so) come from having insulin levels reduced to very low levels anyway, so in my opinion, a complete fast is unnecessary and/or the difficulty vs. benefit ratio is not worth it. Furthermore, fasting-mimicking makes the fast a lot easier and allows me to keep up with my normal level of productivity (in fact, productivity is much higher during these five days).

 

For more info on my general approach to diet, and the diet-mimicking drugs (metformin, SGLT2-inhibitors, rapamycin, acarbose) I use or have experimented with, how I take them, etc. see Note #3 in the appendix of A Diet That Works Well For Everyone

 

What do you guys think of this protocol? Feedback appreciated.

In addition, I also take 1800mg/d of extended-release potassium tablets,

 

Potassium in supplements is limited to 99 mg per cap, because to much of it sitting in one place can damage the stomach walls. Prescription Potassium is higher dose but even riskier because of that. The safe way to supplement high doses of Potassium is using bulk-powders (Potassium citrate, -bicarbonate, or/and -chloride) well disolved in a glass of water, taken throughout the day.

 

Personally did a water-only fast for 21 days at young age, more for spiritual reasons, and not monitoring blood-markers. Find complete fasting easier, since any hunger ceases after 3 days. With chronic diseases 20 years later (PAD, prediabetes..) I again tried a 1 week fast. To my surprise this now even worsened my insulin resistance (now monitoring) for the next year. But maybe only a coincidental association, and insulin resistance anyway worsening despite.

 

 

Edited by pamojja, 24 March 2021 - 11:05 AM.

Potassium in supplements is limited to 99 mg per cap, because to much of it sitting in one place can damage the stomach walls. Prescription Potassium is higher dose but even riskier because of that. The safe way to supplement high doses of Potassium is using bulk-powders (Potassium citrate, -bicarbonate, or/and -chloride) well disolved in a glass of water, taken throughout the day.

 

Personally did a water-only fast for 21 days at young age, more for spiritual reasons, and not monitoring blood-markers. Find complete fasting easier, since any hunger ceases after 3 days. With chronic diseases 20 years later (PAD, prediabetes..) I again tried a 1 week fast. To my surprise this now even worsened my insulin resistance (now monitoring) for the next year. But maybe only a coincidental association, and insulin resistance anyway worsening despite.

 

Extended-release potassium (prescription) does not damage the intestinal lining. Furthermore, with the extended release there is no "risk" as the risk pertains mostly to cardiac conductivitiy issues occurring whenever potassium levels change too fasat.

 

Fasting does worsen insulin resistance in the short term (fatty acids in the plasma), however it should improve it over the long term

I plan on doing my next 5d FMD in 1 week from now. 

This time I might change the peanut butter to 99% dark chocolate. Furthermore, I will also add in the azithromycin for the first time.

We will see how things go

I was considering something like this as well - fasting, but with essential nutrients. Something like CRON but more extreme for 3 to 5 days. Consuming some beneficial supplements, maybe fiber and collagen, a tiny amount of beneficial fat, etc...

I was considering something like this as well - fasting, but with essential nutrients. Something like CRON but more extreme for 3 to 5 days. Consuming some beneficial supplements, maybe fiber and collagen, a tiny amount of beneficial fat, etc...

So a very similar approach to what I have. I am currently on my day 4 of my quarterly FMD. Dasatinib does make you feel like shit though lol for a few hours after taking it

In regards to gut bacteria, can fasting induce autophagy in it and make it more healthy? How long would a fasting need to be for that? On another hand would it be good to kill all gut bacteria by doing a long fast and rebuild the microbiome after? Also what happens to the gut wall? Does fasting make it more porous or the reverse?

 

I've heard several really bad stories with long fasts, personaly I wouldn't do it. I wonder if initially in the first days, the body is not capable of getting enough energy from fat, and catabolizing enough muscle does not make the body continue to function, but after some time, there's not enough FFAs from lipolysis since BF is decreasing quickly, and enough amino acids made available from muscle catabolism, but then some tissues begin to encounter significant problems. There is something called malnutrition and dying from hunger.

In regards to gut bacteria, can fasting induce autophagy in it and make it more healthy? How long would a fasting need to be for that? On another hand would it be good to kill all gut bacteria by doing a long fast and rebuild the microbiome after? Also what happens to the gut wall? Does fasting make it more porous or the reverse?

 

I've heard several really bad stories with long fasts, personaly I wouldn't do it. I wonder if initially in the first days, the body is not capable of getting enough energy from fat, and catabolizing enough muscle does not make the body continue to function, but after some time, there's not enough FFAs from lipolysis since BF is decreasing quickly, and enough amino acids made available from muscle catabolism, but then some tissues begin to encounter significant problems. There is something called malnutrition and dying from hunger.

I´ll take roxithromycin during my fast so I´ll kill all my gut bacteria anyway.

Fasting does induce some autophagy, however at least a 7day water only fast for that to significantly happen (without rapamycin as a cruth).

Depends on how bad your gut health is. Personally, dasatinib certainly makes the gut wall more porous for a few days.

 

This only happens if you have zero body fat or extremely insulin insensitive.

Update: 

Please guys do not use niacin (or dark chocolate) and rapamycin together. Both of these are CYP3A4-inhibitors, and bioavailability and plasma half life might change unpredictably approaching dangerous territory.

Update: 

Please guys do not use niacin (or dark chocolate) and rapamycin together. Both of these are CYP3A4-inhibitors, and bioavailability and plasma half life might change unpredictably approaching dangerous territory.

Also, with the rapamycin it might be wise to check plasma levels. Bioavailability might vary 5-fold between individuals (and if one can afford the rapamycin, one can/should also afford to have plasma levels checked by a private lab).

I suppose you can add IP6 to your protocol as it operates on the P53 and BCL-2:

 

https://pubmed.ncbi....h.gov/18652568/

 

Important note! Since IP6 is a chelating molecule, it can excrete various minerals (Ca, Zn, etc.) from the body. After taking this supplement, you will need to drink a complex of minerals to restore the balance of minerals in the body.

I suppose you can add IP6 to your protocol as it operates on the P53 and BCL-2:

 

https://pubmed.ncbi....h.gov/18652568/

 

Important note! Since IP6 is a chelating molecule, it can excrete various minerals (Ca, Zn, etc.) from the body. After taking this supplement, you will need to drink a complex of minerals to restore the balance of minerals in the body.

If we only had more data (and a trustworthy source...)

Will be starting another round of dasatinib today. 140mg per day (split into 2 daily doses) for 3 days along with Quercetin.

 

Thank you but I (partially) disagree.

By killing senescent cells, new cells from stem cell niches can repopulate the now vacant spots and they will help in producing (at least some) new ECM

Autophagy starts around 24 hours after last meal, unless you are grossly overweight and have huge glycogen reserves.

In people who regularly fast, autophagy can begin as early as 16 hours after last meal.

Fasting past 24 hours induces profound autophagy, even in the brain.

Autophagy starts around 24 hours after last meal, unless you are grossly overweight and have huge glycogen reserves.

In people who regularly fast, autophagy can begin as early as 16 hours after last meal.

Fasting past 24 hours induces profound autophagy, even in the brain.

 

True, however, fasting too often (in humans) can be quite detrimental to hormonal health, wellbeing, energy levels, etc., which might translate in making poorer lifestyle choices (e.g. less exercise) and getting more infections, which in the end might make the tradeoff far from worth it. Furthermore, we do not know how long the world will still exist and in the last years I have left (e.g. 20-40 y) I do not want to live with crappy energy levels, cold, hungry, etc.

 

There certainly are tradeoffs between vitality and longevity.

True, however, fasting too often (in humans) can be quite detrimental to hormonal health, wellbeing, energy levels, etc., which might translate in making poorer lifestyle choices (e.g. less exercise) and getting more infections, which in the end might make the tradeoff far from worth it. Furthermore, we do not know how long the world will still exist and in the last years I have left (e.g. 20-40 y) I do not want to live with crappy energy levels, cold, hungry, etc.

 

There certainly are tradeoffs between vitality and longevity.

 

Interesting, Fasting for 7-20 days has given me a new lease on life. I repeat it every couple of years, and I find my cognition, energy levels, etc... are all markedly improved for some time. Acid reflux - gone! And other aches & pains.

 

Update: Ok, I believe you are talking about daily fasting & calorie restriction. I'd totally agree with that.

Edited by SearchingForAnswers, 01 August 2022 - 06:39 PM.

Interesting, Fasting for 7-20 days has given me a new lease on life. I repeat it every couple of years, and I find my cognition, energy levels, etc... are all markedly improved for some time. Acid reflux - gone! And other aches & pains.

 

Update: Ok, I believe you are talking about daily fasting & calorie restriction. I'd totally agree with that.

 

I have heard the same thing from many others who fast. In fact, I am unsure I have seen any robust data about negative outcomes after fasting, either short-term or multi-day fasting.

With patience, fasting becomes natural. You get better at it. We evolved seasonal food scarcity strategies, like it or not. Fasting is as necessary to human health as sleep, exercise, and diet, but it's on a different timescale.

More challenging (to me) than the occasional food deprivation is how a fast is ended. Eating lightly and slowly ramping out are hard parts. Yet those are key components.

With patience, fasting becomes natural. You get better at it. We evolved seasonal food scarcity strategies, like it or not. Fasting is as necessary to human health as sleep, exercise, and diet, but it's on a different timescale.

More challenging (to me) than the occasional food deprivation is how a fast is ended. Eating lightly and slowly ramping out are hard parts. Yet those are key components.

 

Is that advice about ramping out based upon any studies, or just personal experience?

Both. Refeeding Syndrome is pretty widely studied and not so controversial. The idea is if you fast for too long, and then reintroduce too much food too soon, you'll shock the system, and in extreme cases, people die.

But in my own experience slow is better on the exit, and I'm less likely to binge. Not gorging or bingeing are real challenges, and one reason why supervised fasting in a clinic is recommended. I just can't afford it.

More controversial is the question why bother? No science has affirmed or denied if fasting's short term benefits carry over to longterm. Does fasting of any length increase lifespan? Shrug. Human lifespan fasting studies don't seem likely to occur anytime soon.

Peter Attia MD used to do quarterly seven days fasts until he realized that despite high strength exercising (he is an exercise freak) he had lost several pounds of muscle mass over the years and decided to stop. Now he fasts but not as aggresively, twenty four to fourty eight hours fasts. 

 

Saludos. 

Peter Attia MD used to do quarterly seven days fasts until he realized that despite high strength exercising (he is an exercise freak) he had lost several pounds of muscle mass over the years and decided to stop. Now he fasts but not as aggresively, twenty four to fourty eight hours fasts. 

 

Saludos. 

 

The Fasting mimicking diet is supposed to avoid this problem:

 

https://www.cell.com...4131(15)00224-7

24h is enough for fasting, if it's a dryfast. More effective also if you're already in a ketogenic state to begin with. 1 to 2x/week only, and you'll get all the benefits (stem cell proliferation/autophagy), without loosing any muscle.

Edited by yucca06, 27 June 2023 - 11:57 AM.

Hi,

 

Two of the links in the original post are now dead:

• How To Replace Growth Hormone.

• Supplements Everyone Should Take.

Does anyone have an update for these?

 

Thanks!

 

 

Edited by bob7123, 03 August 2023 - 09:21 AM.

interesting protocol, i've been on a glp-1 for a while and longer fasts hit totally different when appetite is basically gone — makes the mental side easier but i still drag by day 3 without extra electrolytes. with all that potassium you're taking do you notice it helps with the lightheadedness much? also curious if the rapa affects your hunger at all or if that's mostly a non-issue during the fast