#165

It is a bit more nuanced than this though. I am 1Million % anti Covid vax for healthy people (especially young people) whereas I am 100% pro other vaccines.

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#166

Is this the data? Im not sure its showing what you seem to think it is. Can you explain what it’ssupposed to be showing?

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It could be showing the standard deviations for output (hazard ratio) or possibly sdevs for inputs (fitness performance), its not clear, and it’s added in the supplementary data so isn’t really explained.

For example it could be showing the standard deviations for HR for the high/elite groups.
Or it could be showing the sdevs for the fitness performance. That would be an odd result though - because it would be showing that being in the fittest 1% of the elite group has a massive benefit compared to be “averagely elite”. Whereas being in fittest 1% of the High group doesn’t have much benefit compared to being “averagely high”.

#167

Anti-covid vax is not the same as anti-vaxers.
I still get annual flu shots, etc. So I am not anti-vax. But since the only time I have been very sick in the past many decades was after taking the Pfizer vaccine, yes, I am anti-covid shots for me. I have never told or recommended to anyone else not to get the vaccine.

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#168

I agree. Having reservations about a vaccine administration under EUA does not make one an anti-vaxxer. Sorry for using this analogy, I didn’t realize it’s going to strike nerve with members here. It just applies so well in this tread, due to the amount of cognitive biases used by these people, they cannot be ever convinced.

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#169

A. As mentioned, there is not good clinical trial or MR studies that have been provided on this topic

B. So we have to triangulate as best we can and make decision under uncertainty

  1. The human correlations studies are one source

  2. The rich geroscience literature is another

It seems that you either do not agree with A and B or do not think 2 is relevant.

Below are some think you might want to consider / leads to look more into things:

Exercise has been shown to protect from many age-related diseases but fails to extend maximum life span in rodents (16, 17, 21).

Although the evidence clearly shows a greater benefit from calorie restriction compared with exercise on longevity, there remains a significant gap in the literature explaining this disparate effect. The effects of calorie restriction (40) and exercise (6) on age-related diseases and markers of aging have been exhaustively studied independently, while only a limited number have examined calorie restriction and exercise in tandem (26, 36).

Rodent (17) and human studies (32) suggest that increasing energy expenditure via exercise fails to mimic the life-prolonging benefit of consuming fewer calories.

These results showed that mild and moderate calorie restriction were more effective at lowering fasting IGF-1 and insulin levels than exercise, and animals on moderate calorie restriction most closely resembled young animals for measures of hormones and stress-related proteins. In contrast, exercised animals were leaner than calorie-restricted mice and exhibited greater tissue levels of HSPs and oxidative phophorylation complex content in skeletal muscle mitochondria.

The results show that compared with fully-fed controls, ad libitum-fed runners had significantly lower serum IGF-1 levels and less DNA damage, but no improvement in fasting insulin. Animals that were weight matched with ad libitum-fed runners using only mild calorie restriction had similar IGF-1 levels, but significantly lower insulin levels and stress-related proteins. Serum insulin levels were further reduced in mice on mild calorie restriction plus exercise, but stress-related proteins in liver and skeletal muscle from this group tended to be elevated compared with sedentary animals. Animals on moderate calorie restriction that were weight matched to calorie-restricted runners exhibited the greatest reduction in insulin levels, and most closely resembled young animals for measures of stress-related proteins.

Thus, it is possible that some harmful byproduct(s) or consequence(s) associated with exercise “interferes” with the beneficial effects of being lean. Alternatively, calorie restriction may extend life span by a mechanism(s) independent of leanness, and exercise may fail to activate these critical pathways to the same scope or magnitude.

To test the hypothesis that exercise is associated with greater levels of stress-related proteins and oxidative damage than calorie restriction, we measured HSPs, protein carbonyls, and 8-OHdG. Runners (AL/EX and PF4/EX) had elevated HSP25 and HSP70i in skeletal muscle, and HSP25 was elevated in PF4/EX mice in liver compared with sedentary animals. The robust increase in HSPs might suggest greater oxidative stress, need for cellular protection, and/or damage with exercise training, and hence a greater need for protein turnover compared with mild and moderate calorie-restricted animals.

When comparing weight-matched animals, calorie restriction tended to result in more favorable changes to the insulin/IGF-1 axis than exercise.

Recently, Fontana and colleagues (10–12) have examined systemic biomarkers in individuals on a selfimposed low-calorie or low calorie-low protein diet vs. individuals engaged in high-volume exercise for several years. Despite a similar body mass index (10, 12) or fat content (11), long-term calorie restriction and exercise resulted in disparate effects on various parameters related to aging, including thyroid function, systemic inflammation, and growth factors. For instance, individuals engaged in voluntary calorie restriction were found to have lower levels of serum T3 and TNF-α levels than exercisers or a control group consuming a typical Western diet (11). In another study, individuals consuming a low calorie-low protein diet were shown to have a more favorable cancer risk profile than endurance runners or controls, including lower serum IGF-1 and greater levels of dehydroepiandrosterone sulfate and sex-hormone-binding globulin (10). Furthermore, a low-calorie vegan diet resulted in lower blood pressure than exercisers (12). Taken together, the present investigation, coupled with these related studies in humans suggest that at the same relative energy deficit, exercise fails to completely mimic the beneficial changes associated with calorie restriction.

Additional studies are needed to determine whether the failure of exercise to mimic the benefits of calorie restriction and extend life span is due to exercise itself or if a reduction in food intake per se is distinct from an increase in energy expenditure. Along these lines, we found that under clamped food intake conditions, increasing energy expenditure via thermoregulation, rather than exercise, resulted in smaller, leaner mice that had less cancer incidence and progression (22). Similarly, it was shown that compared with controls, rats exposed to cool water for 4 h/day, 5 days/wk consumed 44% more food, but weighed ~20–25% less, and had less sarcoma formation (20). However, the relative energy deficit imposed on these animals did not increase mean or maximum life span compared with controls (20).

Therefore, the available evidence demonstrates that an increase in energy expenditure can attenuate disease risk (20, 22) but does not presently support the notion that an energy expenditure-induced energy deficit slows the rate of biological aging (20).

Along these lines, the CALERIE study (7, 15) has recently reported that 6 mo of calorie restriction or calorie restriction plus exercise resulted in ~10% weight loss were equally effective at reducing fasting insulin, core body temperature, and DNA damage and stimulating skeletal muscle mitochondrial biogenesis.

This one goes in your direction:

Furthermore, an important distinction to be made is that unlike rats and mice, humans often die of cardiovascular complications, including heart disease and stroke, while this is a rare cause of death in rodents (38).

But we know how to control CVD risks via Apo B and inflammation and just a reasonable amount of excercise

https://journals.physiology.org/doi/full/10.1152/ajpregu.00890.2007

  • Rats that exercise regularly will, on average, live longer compared to a group that eats the same amount but does not exercise. This is because exercise prevents some diseases, which allows more individual animals to live out their expected life span.
  • However, when comparing the rats in these two groups that eat the same amount, the longest-lived animals in the exercise group don’t live any longer than the longest-lived rats in the non-exercise group. Taken together, these findings indicate that exercise can prevent an early death from disease in some rats, but does not extend the maximal lifespan of any of the rats.
  • When comparing rats that exercise to those that don’t exercise but eat much less, the longest-lived rats are from the group that ate less.

See also

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

A wealth of scientific literature backs the unique therapeutic benefits of exercise for quality of life, cardiovascular (CV) health, and longevity. Consequently, many have assumed that more exercise is always better. However, chronic excessive endurance exercise might adversely impact CV health. Ultra-endurance races can inflict acute myocardial damage, as evidenced by elevations in troponin and brain natriuretic peptide. Moreover, sudden cardiac arrest occurs more often in marathons and triathlons than in shorter races. Veteran endurance athletes often show abnormal cardiac remodeling with increased risk for myocardial fibrosis and coronary calcification. Chronic excessive exercise has been consistently associated with increased risks of atrial fibrillation (AF), and along with some attenuation of longevity benefits. 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.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431070/

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

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2 years of mild caloric restriction significantly reduces biological age
#170

Calorie restriction extends lifespan. Exercise extends healthspan.
That’s why I do both.

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2 years of mild caloric restriction significantly reduces biological age
#171

Me too!

I actually think that exercise up to a certain extent is an important pillar of extending an individual’s (including my own) max lifespan (but not at the species wide max longevity level - even if CR, Rapa, etc are very good candidates for that).

My issue is with the blind black and white “there is no limit of exercise benefits” beliefs, especially in in the context longevity optimization.

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#172

I posted 3 large human studies that linked exercise directly with healthspan and longevity.

That was not enough to convince you.

Yet somehow you are convinced by a random mix of twitter posts, opinions and animal studies.

That Sir is a textbook definition of cognitive dissonance.

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#173

I never said, look thru the thread, I said the opposite. What I said was based on the evidence the limit seems to be a lot higher than most people realize.

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#174

Yes, but not when begun at mid-life, if I remember correctly from the time when I was completely into CR.

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#175

I think this is probably a true statement, but the more important thing is that the limit is likely much, much higher than 99% of the population ever achieves (or will achieve), so for all intents and purposes I suspect the “limit” doesn’t exist. (although this may be just an expression of my frustration at not increasing my fitness level to what I would like).

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#176

The only evidence for the limit is the existence of the Over Training Syndrome. It’s pretty debilitating although there no studies that I know of that link it to reduced longevity.

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#177

99% of the population are not longevity optimizers though. 99% are not considering taking rapa, and not seeking to in a comprehensive way measure and track their biomarkers.

While what 99% do and do not do is highly relevant for public health policies, etc, they are generally not good benchmarks when when one want to do achieve something extraordinary and world class.

Their health status don’t mean a lot for those of us truly trying to max individual longevity by pulling as many levers in an as optimally way as possible.

My personal intuition is that I and others who are trying to truly maximize longevity might approach and surpass optimal exercise “limits” even if “99%” may not. For example, both Bryan Johnson and Michael Lustgarden are clearly budgeting their amounts of exercise and while doing so in a very thoughtful and disciplined ways they are not doing crazy amounts of exercise. It’s seems to me that both of them would happily add more exercise if they (and Bryan’s case his bench of medical/longevity advisors) thought it would help their longevity further - or do you have a different read on that?

Even the exercise amounts that Peter Attia has been reporting on for himself in recent years is below the elite athlete levels DrBart is pointing to.

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#178

Well, I should be in good shape then.
As a child, I never ate breakfast when I could avoid it. At age 7, I became a latchkey kid (except we never locked doors where I lived) and never ate breakfast again until I joined the Navy at age 18. My BMI when I joined the Navy was ~ 18.6 based on weight/height. My BMI never reached 20 until I was in my 30’s.

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#179

And i think the people you’re vexed with people who are saying the limit might not be as extremely high as you think. And they’re pointing out a few limitations in the studies you quote.

I’m not sure why accusations of trolling and anti-vaxxer are required. It’s just science. The limitations either exist or they don’t.

we reason under circumstances of uncertainty. But its wrong to pretend you’re reasoning with certainty when you’re not. And switching to ad hominen attacks is always a bad look.

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#180

In many ways much that I am sympathetic with @Dr.Bart 's thesis it does not matter that much. Exercise looks to be something which initially has major returns and then diminishing returns, but still positive returns. Then at an endurance point it can have negative returns. However, most people won’t put the effort in to get there.

I think there is a lot that be done with biochemistry as well as diet, sleep and exercise. I am not heavy on the exercise front although I walk quickly and do some calisthenics with additional weight every day.

I walk perhaps 10,000-15,000 steps most day mainly taking my son to school and walking back with him at the end of the day. Also walking with my wife and the dog and to my office and back (which is 8 mins walk from my home). Once all of this has been done I am normally in the 10-15,000 range.

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#181

I continue to wonder about the shape of the benefit curve for various “interventions”. And I think I’m starting to change my mind about VO2Max.

It’s clear that additional X is beneficial when reducing a shortage. This applies to many interventions: sleep, calories, EAA, vitamins, many minerals, sunshine, water, etc. Determining what is too little can be hard but watching for symptoms of shortages can help identify areas for attention. Shortages can be hard to locate because the body adapts and it compensates very well especially when it’s healthy. It’s also hard because I am biased and can get a positive feeling from doing things that I like and believe are beneficial even when they are not.

The tricky part is comes from two places:
(1) can more of the thing have even more but diminishing benefit or does more eventually cause a detriment? Too many calories for too long is a negative. Too much oxygen for too long is a negative. I think but am not certain that everything follows the inverted U shape.

(2) can the body’s ability to adapt be used to change the thresholds of optimal? Can I train my body to be more like it was when I was younger in terms of metabolic flexibility, resilience to stress, immune system efficiency, energy level? Did my body become “old” because I trained it (taught it) to become that way through my diet, exercise, lifestyle?

Based on intuition alone I think exercise is the key to training the body to be more like it was in youth. A gradual increase in training load over time is the key. But keep pushing gradually harder in upward cycles of progress with just enough recovery baked in as the most critical element. Feeling tired and beat down all the time is no way to live (and wouldn’t work anyway). The increased stress on the body may help to identify shortages that the body can no longer compensate for.

I don’t think I can eat or sleep or deep breathe my way to success. Of course I need to support my body as I train it but more is not better…enough is my target. Enough of what I need. Eliminating shortages is the goal. Eliminating unnecessary obstacles to the body to let the body do what it knows how to do.

I’ve decided that accepting a slow decline into oblivion seems like more of what got me here.

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#182

I agree. My plan/hope is to maintain steady fitness rather than accept any decline. Knowing I’ll have to work harder to stand still.

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#183

I’m sure you’re right, i feel 90%+ of people don’t put in the effort. But personally I’m trying to decide whether to do more and I cant quite find the evidence to support it. I’m top 2% for vo2 max, for my age, mostly due to luck and genetics, and I’m not totally convinced more exercise wont be negative. I know quite a few extreme exercisers and they all seem to carry injuries.

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#184

I would argue the additional effort does not produce adequate benefit, but i argue from a position of a greater dependence on chemistry.

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