I’d say that TOR 2 is the issue with everolimus. In theory , it’s the inhibition of TOR 2 from daily rapamycin usage that leads to immunosuppression in renal transplant patients. However, weekly use of everolimus at 5 mg quite clearly improved immune response by 20%.
Once again, the key is dosing and dosing intervals. You can argue that the longevity studies are done with rapamycin, but it can also be argued that the most significant study in humans and immune response was done with everolimus.
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I think that’s a strong argument tong, and not just Okinawan’s but all long lived cultures are high carb, but of course not high refined carb.
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It may be a more accurate statement is “medium carb” - right now I follow mostly fresh vegetables (e.g. spinach salads), nuts, fish (mostly salmon and sardines) and some fruit (mostly berries with yogurt, etc.), Keto granola, and minimize simple carbs, breads, pastas, etc. Reasoning is easy to keep a moderate calorie intake, fewer blood glucose spikes, more nutrient rich foods…
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In a way yes.
Of note, a curiosity is the staple purple sweet potato has a lot of simple sugars in it namely sucrose (1/2 fructose and 1/2 glucose). Although it’s “natural sugar”, if we counted “natural sugar” similar to “added sugar”, it’s actually more than what the AHA recommends as maximum amount of added sugars for adults - if you calculate how much sugar is in just the sweet potatoes alone that they eat per day.
Re: @RapAdmin basically this is jam packed with simple carbs actually!
I believe this can be explained by compounds that act similarly to acarbose in the staple - based on the processes that Okinawans use that alter the chemistry in it.
The purple sweet potato is a nutrient giant and loaded with anthocyanins.
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Yes it is.
Yep yep. Might I add the anthocyanins in purple sweet potato are much more cost effective than supplements and blueberries 
Is that actually purple yam? Not familiar with that one - but beware of confusion. Also, processing may change a lot - leading to possibly different results.
The package states organic purple sweet potato powder, the ad copy states pure natural premium purple yam powder.
Yep unfortunately the industry uses yam and sweet potatoes interchangeably.
I posted briefly here.
Basically, as we age, all of us will have a decline cerebral metabolic rate of glucose use, which is symptomatic with neurodegeneration. Being diabetic massively accelerates this curve.
As a way to ameliorate this loss, generating ketones via diet offer mitochondria an alternate fuel source to promote optimal function. Neurons, Astrocytes and Oligodendrocytes all metabolise ketone bodies
Ketones have all sorts of other pro-longevity signalling pathways.
The diet combined with fasting, of course, blunts glucose spike/AUC, already shown to promote longevity in mice, so that’s an additional freebie.
A ketogenic diet extends longevity and healthspan in adult mice
And by default, a ketogenic diet imposes protein restrictions, and we know quite conclusively in plethora of rodent studies, that protein restriction, most especially BCAA, and furthermore, leucine restriction promotes longevity.
Lifelong restriction of dietary branched-chain amino acids has sex-specific benefits for frailty and lifespan in mice
Metabolomics Study of Isocaloric Different Dietary Patterns on the Life Span in Healthy Population
Promoting Health and Longevity through Diet: From Model Organisms to Humans
https://www.cell.com/action/showPdf?pii=S0092-8674(15)00186-5
Decreased Consumption of Branched-Chain Amino Acids Improves Metabolic Health
“We have determined that reduced dietary BCAAs improves metabolic health even in the absence of significant alterations in the dietary carbohydrate:protein ratio”
Daily caloric restriction limits tumor growth more effectively than caloric cycling regardless of dietary composition
Caloric Restriction vs. Animal-Protein Restriction
“The lifespan extension associated with dietary restriction may be due less to a reduction in calories, and more to a reduction in animal protein (particularly the amino acid leucine, which may accelerate aging via the enzyme TOR).”
As for Okinawans/Sardinans, the long lived “islander” cohorts (yet vastly different diets), from all the literature I’ve read, their longevity signal is majority genetic (enriched lineages), but on the specific dietary side, what they do share in common and is pro longevity is…LOW animal protein and mild CR. This would be very consistent with all the rodent longevity literature.
New Horizons: Dietary protein, ageing and the Okinawan ratio
“Such studies in insects and mice indicate that animals with ad libitum access to low-protein, high-carbohydrate diets have longest lifespans. Remarkably, the optimum content and ratio of dietary protein to carbohydrates for ageing in experimental animals are almost identical to those in the traditional diets of the long-lived people on the island of Okinawa. The energy from their diets was derived from 9% protein and 85% carbohydrates”
Healthy aging diets other than the Mediterranean: A Focus on the Okinawan Diet
So being low carb/ketogenic and overlaying OMAD fasting, I get a combination of benefits and hedges, all associated with longevity:
- Low glucose spikes/AUC.
- Low animal protein (classic ket macros 20% protein, 75% plant fats, < 5% net carbs)
- Ketone bodies generation as alternate compensatory brain fuel for aging, lowers inflammation (NLRP3 inflammasome), HDAC inhibitor, lowers body fat, preserves muscle loss.
- Fasting and all the metabolic benefits, lowering fT3 and metabolic rate. Ghrelin spurs brain neurogenesis.
I feel amazing after 6 yrs on the switch, much leaner, no impediments to muscle build, excellent biomarkers. I have super high energy level. My wife tells me my memory and cognitive is amazing.
But a long way to go to a 100…the hill will only get steeper.
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I’ll add Okinawans + Westernization = about average Japanese life expectancy, thus not sure much is genetics
They already naturally blocked glucose spikes and relatively low protein.
I’ll also add traditionally Okinawans tend to skip dinner. That’s very close to TRF/Ketones when it adds up to 16 hours - especially for lean folks. 
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The Okinawan diet is amazing, super nutrient dense!
I am simply trying to translate the known longevity literature into a human protocol. I do eat a ton of nutrient dense whole foods ONLY, whether wild animal protein, plant fats, or above ground vegetables.
I tell anyone to just start with dumping sugar, simple carbs, and fasting…they confer huge metabolic benefits without doing a full diet reboot.
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Oh and btw I’d be careful with Greger at “NutritionFacts” he can get misleading. The previous name of “NutritionFacts” was “Vegan Research Institute” and he used to promote veganism as a cure for death.
He almost certainly reads “animal meat = bad” with cherry picking. Not saying all the cherries he picks are bad - but I would simply be wary of bias. If one is a pragmatic vegetarian - I don’t have any issues. But he is almost certainly of the ideological type.
Leucine I don’t think is particularly “bad” if you are already doing CR and rapa. There’s also mTOR tissue-specificity in liver, fat, and muscle for leucine while barely staying long enough in your system with an ultra-short half-life. I’m not eating tons of animal meat or taking BCAA supplements to sip Leucine all day (maybe will in very specific situations in the future), but I’ll happily eat some salmon roe and an egg after a workout.
“Preventing hyperphagia by calorie restriction or pair-feeding averts the health costs of a high-BCAA diet.”
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I have zero use for him, don’t subscribe. He just happened to have a page on MTOR and proteins with a great list of references. It was a lazy page grab.
Yes leucine on CR/fasting/rapa is certainly not bad…I eat a good bolus of leucine daily! But it’s a very muted amount. I have never taken a BCAA supplement…my muscle build has exploded on 50g/day animal protein and chronic daily resistance exercise.
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Association is not causation.
Isn’t it equally plausible (my opinion more than plausible but causative), especially if you look at the mountain of research literature on protein, that the underlying longevity signal is LOW protein AUC? That would tie in a diversity of longevity diet cohorts…the central regulator is the protein signal, of course, intimately linked to mTOR?
Hard to tease it out. Could be low protein or perhaps the benefits conferred by fruits, vegetables, nuts, and beans.
Could also have nothing to do with diet but rather low stress, physically active, and good sleep. Who knows.
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Yep, it isn’t. I’m not implying that it must be causative, but we have some evidence - we have plausible mechanisms - mTOR inhibition from calorie restriction and low protein + alpha glucosidase/amylase inhibitors - despite a high carb diet with significant amounts of simple sugars. (Note I also have a wide array of other sub explanations) We also have subgroups that underwent the forces of Westernization after WWII that pushed those subgroups back to about average Japanese life expectancy, which is some evidence for primarily environmental factors and geographical based data.
Could there be some other confounder? Absolutely! And we should look for them (the Japanese researchers have been trying for quite a few decades as they deal with their aging population - I’ve taken enough time to go through research - as well as reviewing commercial claims to sell “Okinawan” based health products which haven’t seem to directly pan out). But in the absence of a better explanation, I think there’s enough to explore further empirically, despite the retrospective nature of the data
Let me understand your logic here.
You will blindly accept that rapmycin will translate to humans, on mice data: NO human data. Yet you won’t accept the thousands of papers on rodents and humans (directly associating with mTOR/IGF-1), showing high protein and reduced longevity, regardless of other dietary macros?
What ties rapamcyin to longevity…mTOR. What drives mTOR in mammals…protein.
Sounds like cherry picking confirmation bias.
I am agnostic a singular longevity pathway in humans.
I too don’t know the answer of course! So why not stack THE best science that is “easily human doable” together and hedge at min 2 interventions, low protein and Rapamycin?
The effects of CR (best longevity in mice) are partly theorized as low protein AUC.
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I see your point but I’m not sure that it’s all that conclusive. There’s evidence that low protein is better under the age of 65 , but higher protein may be better over 65. We’re on rapamycin so we don’t need the extra TOR inhibition.
That being said, all of my protein is from nuts, legumes and salmon. Some chicken thrown in occasionally. Fairly low.
But I don’t think the evidence is conclusive.
As far as my faith in rapamycin is concerned, I’m not married to it, but as of now it’s the best , and most studied, that we’ve got. If sometimes better comes along, I’ll jump on it.
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