#42

I am on your camp 100%! I will only add that conserving fast twitch muscle dont need huge amounts of protein but specific exercises. And the data in humans that we have is that leg power output and grip strength are the biggest predictors.

My only problem is: how do you preserve arteries without doing 5 times a week of cardio and hence consuming a lot of protein? Maybe NO production just to preserve elasticity?

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#43

The Finnish twins study in question somehow found over 20,000 identical twins with different levels of activity. Another recent twins study from Finland reviewed in Outside magazine found only 17 pairs of identical twins out of thousands with diverging activity levels. Which make complete sense. Activity level is genetic.

The premise of the research is that all things being equal in terms of genetics, moderate exercise is better than intense exercise for longevity. But, if another study from Finland found only 17 pairs of twins out of thousands had notable differences in activity level than they are a complete anomaly and should not be considered as typical genetic identical twins, nullifying the premise of the previous research article.

Finland is a small country that I had the pleasure of visiting this past summer. We backpacked a 65 mile loop in Urho Kekkosen National Park, 250 km north of the article circle. It was beautiful and included a carpet of blueberries everywhere we hiked. We also visited relatives in Helsinki and chatted about the exercise habits of North American and Fins. It seemed fairly equivalent when similar demographic groups were compared. Although, we did not discuss exercise habits of identical twins :slightly_smiling_face:

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#44

Have you investigated the potential major downsides for longevity with CR and protein restriction and how if possible to mitigate them?

I don’t know, but for example low BMD and osteoporosis. It would be awfully pointless to do CR+PR for 20-30 yrs but then have brittle bones and fall and then break a hip and 50% expected to die. I don’t know if this is a side effect and how it can be mitigated (BJ is in the top percentile for BMD e.g).

#45

This is part of the reason why I’m only on the mild side of CR and protein restriction

I do resistance training 3x a week (with extra legs and back focus), with good emphasis and prioritization of sleep and take creatine to enhance muscle synthesis, etc and am doing somewhat ok on muscle/lean mass and think it’s helping me with bones and try to ruck regulatory and do some of my zone 2 running instead of cycling.

I also do DEXA to monitor (and less often MRI).

I’ve looked into and cycled in and off calcium and K vitamin supplements, but need to dial in that protocol more (while taking into account CVD).

I also do a lot of things that keep my balance excellent and intent to keep “training it” throughout my life.

I do think what you mention is a real risk for people who have become frail today - and might also be in 25-40 years when I’m at the age when those things would based on current medicine start getting exponentially riskier for me.

At the same time, I also think a lot will likely happen over the next three decades to offset the risks of (a) ending up with sarcopenia and osteoporosis and (b) avoiding the risks from it and intervening if falls leads to injuries, etc.

So again, just trying to balance different types of risks and optimize a path of trade-offs

And will keep updating approaches and protocols as we learn more each year and decade.

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#46

And he is vegan and on mild CR.

Also think Michael Lustgarten is an example that transistor muscle retention is possible with limited calories and protein?

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#47

Ridiculous. There are plenty of studies that show the huge benefits of exercise. Check the VO2 Max studies.

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#48

Cool beans.
Can you think of any other negative effect that CR+PR people need to consider other than hip fractures downstream from low BMD and balance? Immune system?

It feels like the problems from CR+PR is basically unaware of historical issues people have had from the lifestyle. Knock on wood, they’ve been trailblazers in this regard, so all the respect to them.

Measuring BMD, taking supplements and specific exercise, maybe drugs one day, all are good ideas.

Magnitude of longevity boost effect will probably be even greater if balance (neurodegeneration + muscle) and BMD are taken care of. Low BMD and hip fracture risk is a drag on max and median lifespan for sure. Wondering what else. :thinking:

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#49

Think this one is real.

Also think that for some people it could impact mental health in a negative direction.

Certain parts of the body where cell renewal may be more important than on average should perhaps be monitored extra well, like pancreas function? (As one probably should if on rapamycin too…)

(Of course fewer calories means nutrient density matters more - so CRON and not just CR to avoid any deficiencies. And extra valuable with biomarkers and data collection).

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#50

100% with you that high V02 max is good for health, healthspan and probably for longevity too

But do you have any studies or data that can help separate out whether that correlation is because expertise => longevity and not:

genetics and good health => high V02 max

and/or

people who are sick/less healthy (and either had some genetic lottery issues or just cannot exercise as much) => lower V02 Max?

Ie we know that :open_umbrella: is correlated with :cloud_with_rain:

But it’s not :open_umbrella: => :cloud_with_rain:

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#51

The results from the VO2 Max association study wasn’t that impressive, and it was measuring in 50 year olds over 5 yrs, saying nothing about maximum lifespan → centenarian, etc.

Measuring VO2 max effect on overall relative mortality over a few years in 50 year olds is so flawed. Besides, most of the “benefit”, was at a normal level.

VO2Maxxing rests on a non-geroscience approach to avoid age-related decline in VO2 max by having a high one to begin with. It is accepting decline and compensating. Is age-related decline in VO2 max driven by few people who are hospitalized, sick, or is the trend in decline steady for the average person?

No one’s fact checking Peter Attia on this?

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#52

I believe he’s also on exogenous testosterone, which has massive effects on BMD.

He’s also not entirely forthcoming with all of his results. I.e. the perfect results he puts out were not all taken at the same time. For example, calorie restriction would lower testosterone, yet his is claimed to be 800+.

#53

Not anymore, as a result of decreasing his amount of CR.

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#54

@Steve_Spencer what are your thoughts on this post and then one I wrote in reply to your post?

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#55

Are there any studies that correlate Rapamycin with Max VO2? I’m not sure if it is fair to use RBC, hematocrit, and hemoglobin to indicate the state of ones VO2 max. But, there definitely a scientific correlation between VO2 max and these blood tests. When EPO is injected the resulting increase in hemoglobin, etc. correlates with a higher VO2 max. This increase in VO2 max is not accompanied by any increase in activity. It is strictly because of the EPO. It seems like if Rapamycin positively effected longevity through an increase in VO2 max that it would be visible in the hemoglobin and associated blood markers. This would be true across all activity levels.

I have seen no movement in my RBC’s, hematocrit, or hemoglobin after 6 months on Rapa. But, my training intensity has increased along with hours logged. My joints, flexibility, and recovery are allowing the bump. This raises the question, is it the autophagy aspect of Rapa that gives the bump that allows the maintenance of VO2 max while aging? And could that be what has allowed mice to remain active thus increasing their longevity?

Humans are sentient and quality of life in terms of mobility and ambulation are way more impactful for us later in life than for simple mice. Whether a low activity person or highly active person this aspect of Rapa could be way more impactful on healthspan and sense of well being correlating with increased longevity in humans.

I have my doubts about the validity of the Finnish twins longevity study. But, an interesting thought experiment would be hypothesizing the effect of Rapa on the more active twin

#56

Honestly, no thoughts yet. I have to take it all in. I need to read the various studies, but it’s hard to find the time. Nonetheless, I appreciate your contribution.

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#57

Also, I remember reading some articles and listening to podcasts about general health and longevity in colder climes. I’m sure Helsinki never gets as hot as Mandalay and the air is probably clean, which it’s generally not in the triangle of China, Myanmar, Thailand with winds from Bangladesh in the mix.
So, many unaccounted variables could have significantly impacted the study etc.

#58

If I’m understanding correctly, I’m not sure that this is correct. Benefits of Rapa may be at the organ or tissue level. For example, less fibrosis allowing better lung expansion, better perfusion of muscles, better handling of oxidative stress, better mitochondria, more efficient glycolysis etc. I don’t think they would reflect in RBC, HCT etc. (And also, those things are benefits of exercise, so if you’re regularly exercising, most people will see them improve without Rapamycin).

Thanks for the information. He must be a real outlier to have total T of ~800 (I believe that’s a result he’s often shared?) while maintaining year-round low body fat and a CR diet. I can appreciate that lowering stress, improving sleep, micronutrients etc would help, but that’s still upper percentile.

#59

I think you might be right with the people on large 25-30% or larger CR deficit level, but are you sure that is the case for people like Michael Lustgarten and Bryan Johnson on a more mild CR regime?

The recent gold standard, randomized, controlled trial does suggest that milder CR (at least for 2 years) would NOT lower people’s testosterone:

Effect of Calorie Restriction on Mood, Quality of Life, Sleep, and Sexual Function in Healthy Nonobese Adults

The CALERIE 2 Randomized Clinical Trial

Changes in luteinizing hormone, total testosterone, and follicle-stimulating hormone levels did not differ significantly between the groups

(Free testosterone dipped a bit at 12month, but was not different from controls after 24 months of CR)

The CALERIE (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy) trial was the first randomized controlled trial (RCT) of long-term calorie restriction in non-obese humans, funded by the National Institutes of Health (NIH)

The study was designed and conducted by top research institutions, including Duke University, Pennington Biomedical Research Center, and Tufts University, ensuring high scientific credibility and methodological rigor.

https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2517920

#60

Recent video from Lustgarten show that lower BMI is associated with higher testosterone

People with ripped physiques not from diet and gym, e.g sand divers in cameroon have high levels of muscle mass at the same time. Low bodyfat and high muscle mass has probably been a common phenotype. If I’ll guess I don’t think CR decrease testosterone as long as it’s not high enough or as long as it’s somewhat intermittent.

edit: There might be a tradeoff where adding TRT+GLP-1 on top of more CR might be beneficial but most wouldn’t do that probably.

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#61

No TRT or gym, and looks like some CR, but it’s probably possible to have hypogonadism or similar at high muscle mass (after all, it’s supraphysiological amounts of T that steroid users use).

(I might be repeating something I’ve said before as I get deja vu).

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