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.
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For fostering self-discipline I simply do not eat.
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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.
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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.
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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).
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In addition, I also take 1800mg/d of extended-release potassium tablets, 600mg elemental magnesium, 200mg calcium, and salt.
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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.
140mg per day (split into 2 daily doses) for 3 days along with Quercetin.
