Neither does Rapamycin in humans. Both very hard RCT studies to conduct. Doesn’t mean we cannot take a leap of faith on the science available, even if in other species, for possible human benefit. I think all of us here are longevity hackers, each an n=1, motivated enough knowing there is no do over.
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Rapa shows a strong and consistent benefit in animal models. Keto… not so much.
What do you define as a high VO2 max?
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I am listening to the Rhonda Patrick podcast with Eric verdin… Lifespan improvement with Keto, but even better memory and cognitive benefits in their studies. Not sure how large the sample size was.
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I have large database of Ketogenic, CR and Fasting Regime papers in various animal models.
Here are a few papers in mice to show that many of these studies show longevity benefits similar to Rapamycin (15% +/-). The fundamental mechanisms underpinning healthspan and lifespan improvement in ketogenic/fasting regimes is similar to Rapamycin, namely blunting mTOR, but also extend further to other beneficial pathways: protein acetylation, HDAC, tumour suppressor proteins, Foxo3a, etc. Rapamycin is akin to a CR mimetic (mTOR depression), and ketone/fasting is pseudo-hybrid regime of a quasi CR mimetic. Doing full on CR, although many studies have shown even SUPERIOR to Rapamycin lifespan extension, I’m not willing to lower my BMI and fragility risk to that extreme.
So I am currently combining Rapamycin, Ketogenic, and Fasting (One Meal a Day) as one holistic lifespan intervention. Hoping for some synergistic amplitude effects.
I’ve looked at extended fasting, water fasts, FMD (Fast Mimicking Diets), but too afraid to eat into precious skeletal muscle reserve, only to have to do mega gorging re-feeds and resistance exercise to build weight and muscle back up to set point. This yo yo modality I haven’t bought into. If I had cancer though, I would entertain.
A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice
https://www.cell.com/cell-metabolism/fulltext/S1550-4131(17)30490-4
Fasting drives the metabolic, molecular and geroprotective effects of a calorie-restricted diet in mice
Daily Fasting Improves Health and Survival in Male Mice Independent of Diet Composition and Calories
Daily caloric restriction limits tumor growth more effectively than caloric cycling regardless of dietary composition
The effect of a ketogenic diet and synergy with Rapamycin in a mouse model of breast cancer
Beta-hydroxybutyrate as an Anti-Aging Metabolite (General Background Paper)
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Ah yes, I see the mistake you’re making. When calorie intake is matched, Keto fails to yield consistent longevity results. Matt discusses the experimental design flaws around the 25 minute mark and talks specifically about Keto at 36 minutes:
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I haven’t researched this in depth - but irrespective of the longevity benefits - it seems that the brain / memory / cognition benefits of a keto diet are pretty compelling in the studies I’ve seen. Do you have data contradicting that?
I tried Keto but found it hard without increasing protein (and fats of course) consumption considerably… which didn’t help my already high cholesterol levels…
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Yes, indeed, there is significant research in mice AND humans of the cognitive benefits of ketones.
Ketogenic diet reduces mid-life mortality and improves memory in aging mice
A ketogenic drink improves cognition in mild cognitive impairment: Results of a 6-month RCT
Modified Ketogenic Diet Is Associated With Improved Cerebrospinal Fluid Biomarker Profile, Cerebral Perfusion, And Cerebral Ketone Body Uptake In Older Adults At-Risk For Alzheimer’s Disease: A Pilot Study
I initially adopted the diet and fasting overlay for cognitive protection, but have since learned of their mutually independent systemic, cellular wide benefits to all cause mortality. Keto and fasting triggers pathways that impact EVERY cell in the body, encompassing mTOR reduction and beyond. I’ve referenced earlier.
Keto can be hard, but I found one meal a day MUCH harder. The Ghrelin hunger signal begins first thing in the morning and roars throughout the day until my single meal, dinner. It takes great fortitude to ignore the signal (it’s been 5 yrs for me, I have adapted, but takes massive self discipline). It can be very anti-social.
As for keto and protein, it’s really VERY easy if you stick to the macro targets and very selective food groups. First of all, no diet is ketogenic unless you ACTUALLY measure your blood BHB levels (you can buy sticks and meter just like glucose). So low carb does NOT mean ketogenic! Because typically people will overload protein macros, and this kills ketosis (ie Atkins). High fat, low protein, little to no carbs is the achievable keto recipe reference point.
The basic macros are 75% fat, 20% protein, and << 5% carbs. Now there is “dirty” keto, which most people associate keto with…animal fats to achieve the fat macros. But this regime is highly atherogenic. I practice “clean keto”, so my fats are all plant fat based. I only eat very lean animal proteins, whether red meat, chicken, or seafood. These are not hard to find. My typical meal is a whole avocado, handful of nuts (macadamia, walnut, pistacchio, pecan, pumpkin), EVOO, and a few squares of 100% dark chocolate (a super food unto itself). That is the fat bolus. Then max 50-75g net animal protein (of course one cannot have plant protein since it’s very carby). If you’re worried about “protein” targets to muscle maintenance, I put no real stock in that because I use resistance exercise as my muscle builder, not relying on amino acids. As Blagosklonny told me once, “amino acids do not make muscles stronger, exercise does. And Rapamycin potentiates strength”. I eat max daily 50-75g protein (70 kg) and have hugely increased my muscle build over the years. And finally, as much above ground leafy green, low carb veggies as one can eat to satiation. No fruits, other than sometimes low glycemic such as blueberries/blackberries. One can get all the nutritional benefits in fruit from vegetables, so you’d not be missing out. That’s it. If you find you tend to want more protein, its because you’re not getting satiated with the fats and low carb veggies…that is the fine balance. So it takes some iteration, tweaking macros, checking blood BHB, until you find your “keto window”, and then you have your guardrails, don’t need to continuously measure your blood ketones. It took me a few months to settle into the food groups.
I track my lipids regularly. I only look at TG/HDL, and remnant cholesterol (TC-LDL-HDL) as CVD proxies. All excellent (people may wonder about the CVD risk having all that “fat”, but as stated, pursue the plant fat based route).
Many people do keto just for weight loss…I can confirm amazing efficacy. I lost 50 lbs in 6 months, and have been weight stable since, tweaking increasing muscle mass with lowering body fat %. I went from high BMI (approx 30), high body fat, low muscle to a current BMI around 22-23, very muscular, very lean.
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My approach is very similar, though I need more fat to maintain my weight with 22 BMI (about 3000 kcal). I have done regular FMD 5-day fasts for the past 5 years, mostly monthly and now every 6 weeks. Muscle loss is not a problem.
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That’s amazing. I may explore extended fasts in the future.
Does your weight change much in the most extreme fasting regiments?
For sure you’d be in a state of ketosis during the extended fasts.
Yes, I generally get to 2-3.5 mmol ketones by the end of the fast, and my usual on a keto diet is 1-2 mmol. I usually lose about 5 pounds, about half of which is water or intestinal contents (which I gain back within a day or so). Almost all the rest of the weight loss is fat, which makes sense since my total calorie deficit is about 10,000 kcal over the 5 days. If there is any muscle loss (which I’ve never noticed), I quickly regain it.
What’s your motivation, anything in particular, or general longevity signalling?
The science in humans of course is not settled on many (any?) of the interventions practiced on this forum.
My n=1 keto/fasting is biased to daily bathing in ketones/hormetic stress vs longer gap periodic. So I’m turning down mTOR daily (CR burst mimetic), but then overlaying a longer intermittent signal with Rapamycin.
It also indirectly forces me to be highly disciplined in my daily regiment vs “cheating” in between.
I read a lot of Valter Longos fasting work, it’s amazing. The anti-cancer, immune resets, autophagy, improved metabolic health, from simply nutritional signalling.
Are you tracking any biomarkers to give you any insight into your interventions?
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With the FMD, I’ll looking for immunomodulation for type 1 diabetes. Over the last 5 years of its late onset, the disease has not progressed and possibly slightly improved, so I’ll continue what I’m doing. BTW, doctors consider progression of type 1 (continued destruction of beta cells) inevitable after about the first 6 months.
Fibromuscular dysplasia? Or?
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FMD is fast-mimicking diet
Wow, is there some clinical precedence for FMD and/or other nutritional signalling protocols to ameliorate T1D symptoms/beta cell destruction?
Kudos to fasting hormesis!
There is much research on successful management of T2D with a ketogenic diet, but as you know, much riskier with T1D. Is this something you’ve ever considered?
Wishing you much success.
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Thanks, I’ll read this carefully. I’ve heard that SGLT-2 inhibitors can cause euglycemic ketoacidosis in type 1 diabetics, so I’m definitely avoiding them. I do monitor my blood glucose closely, and my ketones occasionally, and the latter are never a problem.
Often doctors don’t take into account the presence of ketones when thinking that diabetics are hypoglycemic: one can function perfectly well at a lower blood glucose when ketones are present. For me, 60 mg/dL glucose is where I start to feel bad; without ketones, I’d start to feel bad at 75.
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Saw this today - another inspiring story:
You can have your Shaun White, your Lindsey Jacobellis, your Chloe Kim. Sure, they’re Olympic gold medalists and, in White’s case, a snowboarding legend.
But they’re kids — even the 35-year-old White — compared with Dick Schulze who, at age 76, defies both age and gravity.
He is the country’s oldest competitive snowboarder, a relative late bloomer who didn’t take up the sport until his 50s and plans, despite a titanium knee and a fall that crumpled his helmet and blacked him out, to keep going until he hits at least 100.
…
Americans are living longer and generally leading healthier and more active lives. …
There are several reasons for the rise of autumnal athleticism, said Jennifer Ailshire, an associate professor of gerontology at USC. Better diet. Better training and physical conditioning. Less exposure to disease. (Notwithstanding the current pandemic.)
“Our conditions of living have improved,” said Ailshire. “We’re less likely to have accidents and injuries than in the past. Our world is a healthier, safer world than it used to be.
“In terms of the world of athletics,” she went on, “exercise science and the science behind competition have also improved over time, so that athletes just have more longevity than they’ve ever had before.”
Maybe Schulze snowboarding to the century mark isn’t that farfetched. The home page of the National Senior Games Assn., which organizes events for athletes 50 and older, recently featured a 97-year-old swimmer, a 96-year-old track and field competitor, a 95-year-old cyclist and a triathlete who, at age 55, is a mere sprout.
…
Another important reason for the growing ranks of senior athletes is a shift in the mindset of older Americans, who no longer see aging as a sadly inevitable slide into decline and decrepitude.
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A 75 year old marathon runner:
How about this 86 yr old on the resistance exercise side.
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Mick Jagger… at 78 seems to be aging reasonably well. Of course, dancing on a stage in front of 50,000 people might increase the adrenaline a bit… but I must say he does move like a person much younger than him. I know people 20 years younger than him (mostly people a lot heavier than he is) that don’t move as well as he does.
A future poster child for rapamycin 
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