Exercise not effective?

[Mikhail V. Blagosklonny has just tweeted the following

Can this be correct? I thought the positive effects of exercise on life extension were proven.


Nothing has been proven in humans to extend “maximal lifespan.”

I believe he’s referring to the biological limit. I’m guessing he’s postulating about whether a human intervention exists akin to what Rapamycin does to mice.

Here’s a study on exercise in mice:

Here’s a paper comparing exercise to DR in rats:

But generally, studies in mice do not show significant maximal lifespan extension with exercise. Nothing like CR or Rapamycin.

In humans:

Endurance exercise, VO2max, is proven in multitude of studies to reduce all cause mortality and extend lifespan in humans. And muscle strength is also associated with increased lifespan.

Generally yes, exercise is going to increase human healthspan and modest gains in lifespan…5-10%. But not been shown to produce consistent large lifespan extension like Rapamycin in mice.

We humans are still searching for the holy grail intervention(s) that increase maximal lifespan.


Don’t care. Exercise extends healthspan, and reduces frailty and all-cause mortality. You don’t want to live to be 100 having been pushed around in a wheelchair for the last decades of your life.


When comparing:

  1. mild CR
  2. exercise
  3. mild CR+exercise
  4. moderate CR

moderate CR is best on measures of stress-related proteins:

Animals on moderate calorie restriction […] most closely resembled young animals for measures of stress-related proteins.

but they did not go one step further and measure data moderate CR + exercise.

Since we know muscle and aerobic fitness is important for healthspan, and Attia’s podcast makes a strong argument for maximizing your fitness, it seems that a balance of CR and fitness is best for maximizing lifespan and healthspan.

However, since we have a CR mimetic in rapamycin, why not eat at maintenance levels on rapa and maximize fitness? If you restrict calories continually (fasting is a different issue), you will miss important nutrients (see Ames triage theory), leading to reduced healthspan.


We know CR and Rapamycin work on different beneficial pathways, so in some way, I want to harness both (hedging, stack and hack). Not a huge fan of full on CR for major reset weight/muscle mass setpoint; would much rather leverage fasting (Lamming). Specifically, fasting with complete nutritional and muscle maintenance with minor weight loss (trade my residual body fat for muscle on the setpoint deviation), plus exercise, and rapamycin is the trifecta needle I am trying to thread…harness all and sneak through. Actually, I have a DEXA tomorrow.

In phase 1, objective met with loss of 50 lbs on keto/OMAD whilst daily aerobic/resistance exercise, with huge gain in muscle mass/strength and VO2 aerobic expansion, at expense of body fat. Been weight stable for last few years. Excellent biomarkers and overall healthspan status, phase 1 complete (57 yo).

In phase 2, overlay rapamycin, slight calorie reduction and slight increase in fasting (quasi moderate CR?), increase resistance loading and trade residual fat for muscle to a lower weight setpoint. Maintain biomarkers and healthspan status. 12-24 month project.


Maximal lifespan past a biological limit (possibly 120-125 with current bandaid-type medical advances) is true.

But it’s low-hanging fruit for sedentary vs exercise when the limit is in play.

CDC has done a long review of exercise and multi-disease prevention. It’s a no-brainer for increasing disability-adjusted life years.


The optimal dose of exercise remains unknown and probably differs among individuals. Current studies suggest that 2.5 to 5 hours/week of moderate or vigorous physical activity will confer maximal benefits; >10 hours/week may reduce these health benefits.

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Yep, I mean there are actually a decent amount of female Chinese centenarians with osteoporosis and foot binding. But they don’t die because they literally don’t fall down.

They practice calorie restriction inadvertently and don’t die from hip fractures because they are literally disabled. But disability-adjusted life years are near zero. They also are much more likely to have dementia.

Exercise is a proven brain chemical bath full of nootropics that work.

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Personally, I aim for 300 minutes per week (I do 150 of HIIT or high intensity most of the time to sub) of moderate aerobic plus 2-3x a week of muscle building (can be concurrent with circuit training, I focus on strength at near 95% 1RM to trigger a strong signal to the muscle, not hypertrophy - my neurons are the most important to me personally), and balance/coordination exercise (can be combined with aerobic) is where the marginal utility of more exercise is probably not particularly significant.

Now if you are risk adverse, you may not want to do risky sports or near 100% 1RM like I do. Injuries are the worst and I have perfect form using algorithms, gait analysis, and consulted PhDs in biomechanics so I keep injury prevention at the top with the best technology and experts can offer by arming myself with knowledge (so I don’t get scammed by those looking for money) and money. Don’t lift with ego.

It’s pretty hard to overtrain but if you are a pro athlete or semi pro athlete who can’t take at least a day of the week for rest, you might be overtraining.

Here’s my background - I can show extensive proof privately to rapadmin I used to be ~200 lbs at ~6% body fat before, so I know how to gain mass for pure aesthetics without anabolic steroids - I also formerly had a NASM certification - for CPT with specialization - and exercise physiology research experience - so I consider myself an “exercise expert” at a graduate level but not the super in-depth PhD stuff so I’ll stay in my line regarding in-depth PhD level exercise research. I also have proof of applying it in practice by literally gaining 50 lbs of muscle over several years with DEXA scans - although muscle mass is not my current goal.

1000%…“proven”. My primary focus is cognitive preservation…no use having a great shell without the brain that is the soul of my “life”.


I’ve been doing intense daily aerobic, approx 4-5 hrs/week for years, don’t plan on stopping. I don’t put my resistance exercise in same cardio bucket, although certain sets can definitely get heart elevated for a brief period of time, but nowhere near aerobic.

Chronic high aerobic exercisers (marathoners, etc) are prone to higher AFIB rates and myocardial fibrosis/scarring, although without a doubt, they live much longer than average. A triathlete friend of mine (recreational, not a pro) has been a chronic volume exerciser (75 miles/week +/- just running, 10+hrs/week total cardio for certain) most of his life (57 yo). He started having AFIB recently. Cardiologist said it “wasn’t associated” with his exercise, no reason to stop. I have my doubts re risk, told him to get a CAC to check under the hood (cardiologist didn’t suggest to him). He’s in a current re-assessment period.


I would also note master athletes can get atherosclerosis too. The incidence of subclinical atherosclerosis is actually very high in master athletes but they are still less likely to die barring genetic disorders like HOCM.

Let me repeat this - you can still die in your 30s as a master athlete from heart attack with no HOCM. Heart attack is a top 5 killer in your 30s even if you are a master athlete. Period.


Endurance sport athletes are prone to afib. However, they also tend to take supplements and illicit drugs that are banned. I can tell you from a short sports med experience - most of the athletes were taking something - not just creatine or whey - they admit it to their doctors as long as it’s private. They also feel more comfortable with a NASM guy who has research experience and a huge biochem/pharma geek to disclose because I can actually monitor it and make suggestions for consults instead of the routine checklist algorithm medicine. I also had a private $850/hr consult with a B-list celebrity on steroids once from an athlete referral. I ended up finding a lot of problems that nobody thought of looking for because they are “healthy”.

There are also chronic autonomic activation and chronic electrolyte abnormalities along with fibrosis from overtraining that may be factors.

The cardiologist is wrong but note cardiologists especially heart failure/EP folks tend to deal with unhealthy people. I found every single cardiologist I rotated with is not familiar with deep-in-the-weeds prevention medicine because of very low priority reading. If you know a humble cardiologist personally who is self-aware of limitations - they’ll readily admit it privately. Feel free to check and verify yourself - I don’t claim to be the arbiter of truth.

I also found as a med student (way back) I was better at reading EKGs than the residents (including upper level) because I went through every single “Life in the Fast Line” EKGs and Dubin’s which no one bothers to read fully because they rely on the machine (can be wrong sometimes), but not as good as the cardiologists (probably just from lack of experience). But I did better than the fellows (not enough experience with attendings to say for sure) on “healthy people” EKGs because I read a lot more of those - I once thought of making it algorithmically from former ML experience, clinical gestalt, and EKG experience into a startup to read EKGs for “healthy people”, but turns out its unlikely insurance will pay for it enough to raise VC money even if it gets FDA approved.

I don’t rely on machines and algorithms because I literally have experience in machine vision and deep learning for medical imaging. I also don’t trust the experts on certain things where I know they have limitations. This ends up catching the last 5-10% of things specialist experts and primary care folks often miss in “healthy people”. You won’t find many physicians that practice this type of medicine because it doesn’t pay.

This has further been confirmed by my experience of physicians not reading EKGs or imaging and relying too much on the specialist “experts” who do not seem to read on prevention for “healthy people”.

And my friends cardiologist is a “sports cardiologist”! I’ve read way too much exercise/CVD literature to keep quiet, and strongly advised him to pause and do full workup, go much deeper.

A little before your time, but Jim Fixx inspired me to take up jogging as a health and fitness sport. It was a total shock at the time when he died of a heart attack while running.

James Fuller Fixx (April 23, 1932 – July 20, 1984) was an American who wrote the 1977 best-selling book The Complete Book of Running. He is credited with helping start America’s fitness revolution by popularizing the sport of running and demonstrating the health benefits of regular jogging. He died of a heart attack while jogging at 52 years of age; his genetic predisposition for heart problems and other previous lifestyle factors may have caused his heart attack.Jim Fixx - Wikipedia
“Jim Fixx - Wikipedia”

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It’s okay if he’s truly humble to ask the cardiologist. But in my experience, some cardiologists get really sensitive about their limitations (despite objective evidence and constructive criticism in a respectful manner) and I don’t blame them - you sort of have a big ego to deal with dying patients all the time and become a cardiologist with such crazy competition for a cardiology fellowship and chase a prestigious position in cardiology.

It’s even more so with patients partly because of reputation issues, but at least the patients usually don’t know enough medicine. A simple way a nonphysician can check is to ask a heart failure cardiologist (make sure they are trustworthy and humble about their limitations) about how apoB or low estrogen (ER-alpha receptor) in men works for subclinical atherosclerosis or CVD risk instead of LDL. A lot of them (not all) put it in low priority reading statistically.

When it’s another physician with objective evidence in cardio-related experience they lack - it can become sensitive even when done in private when I’m trying to preserve any negative rep from embarrassment.

My healthcare professional team includes a cardiologist, but even doctors aren’t gods…they don’t have all the answers. I see them as coaches/counsellors to help guide the journey. The only person responsible for my successful longevity is ME…I need to own it and search for deeper insights/interventions/risk stratification.


How tall are you? 5’10 Layne Norton was ~200 lbs at a dehydrated stage weight which is near elite for a natural body builder.

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I have five nephews way younger than me. They all have heart stents.
Color me cynical, but I have never seen a cardiologist that didn’t say “You know angiograms are the “gold standard”, you should probably have one”. " And we can also put in stents at the same time if you need them". Every one of my nephews who thought they would just get an angiogram got one or more stents at the same time. Stents do not prevent heart attacks or extend life span. I am not sure they even provide any health benefits. This is sad because as an engineer I thought stents would be miracle workers when they were first introduced.


What is it about us engineers…most of us (myself included) are highly cynical! Unless we see the cold hard data, we just don’t accept anything at face value.