Healthspan Without Lifespan?

[TomBAvoider]

Nice overview [of CR and Exercise], MR! With time, I've grown ever more skeptical about extrapolating almost anything from rodents to humans. It's gotten so bad, that when I see a paper that says "in mice" or rats, I don't even bother to read it. To me, studies done in mice or rats apply to mice or rats, and that's that - and only to a given strain of rodent. 

 

I am curious about the tension between lifespan and healthspan. It was always assumed commonsensically, that you lived longer, because you are healthier - it seems so obvious, it's almost a tautology. I remember, back in the day, you yourself, MR, have said things to that effect. But I think there's more and more evidence that this just ain't so. Starting with the observation that people reach the extreme old age status along different paths - there are the disease avoiders, the survivors and the copers, the postponers. If they all reach roughly the same age, then it clearly mitigates against the idea of healthspan being the only determinant of lifespan. That of course is complicated by genetic potential, in the same way that f.ex. a short lived species individual may be healthy but still have a short life span. So ideally there is only one way of ascertaining that, and it would be in the same individual - does health status irrevocably determine lifespan? Or perhaps, it might also be true that you could be a fairly sickly individual and live about as long as you'd live as a healthy one, with the only difference being QOL. It might be along a spectrum - if you are sick to a large enough degree it would affect your lifespan, but anything outside of some treshold is irrelevant - you're just a healthier or less healthy corpse having live a given amout of time.

 

The squaring of the curve question wrt. exercise therefore is another way of addressing the question of how close the relationship between lifespan and healthspan is. 

[Mechanism]

Edited

[TomBAvoider]

Al P. just posted this study: PMID: 29020626 "Uncoupling of Metabolic Health from Longevity through Genetic Alteration of Adipose Tissue Lipid-Binding Proteins." 

 

Quote:

 

"Abstract

Deterioration of metabolic health is a hallmark of aging and generally assumed to be detrimental to longevity. Exposure to a high-calorie diet impairs metabolism and accelerates aging; conversely, calorie restriction (CR) prevents age-related metabolic diseases and extends lifespan. However, it is unclear whether preservation of metabolic health is sufficient to extend lifespan. We utilized a genetic mouse model lacking Fabp4/5 that confers protection against metabolic diseases and shares molecular and lipidomic features with CR to address this question. Fabp-deficient mice exhibit extended metabolic healthspan, with protection against insulin resistance and glucose intolerance, inflammation, deterioration of adipose tissue integrity, and fatty liver disease. Surprisingly, however, Fabp-deficient mice did not exhibit any extension of lifespan. These data indicate that extension of metabolic healthspan in the absence of CR can be uncoupled from lifespan, indicating the potential for independent drivers of these pathways, at least in laboratory mice."

 

This is another entry in the question of the relationship between healthspan and lifespan. Previously, we've seen it addressed with the variable of exercise. Here we have it addressed with metabolism. If neither exercise, nor optimal metabolic health address longevity, then perhaps it's an argument against Dean's thesis that CR does nothing to extend lifespan and his claim that if you merely adhere to healthy living principles, you will get as much lifespan out of it as if you underwent CR. Of course, major - MAJOR - caveat, this is in mice. 

 

Many of us here (myself included) have claimed that we engage in CR not so much because we believe we'll live any longer, but simply because we want to maitain health. In other words, I'd rather live to X (X being whatever my genes determine - 80, 90, 100, etc.) being HEALTHY than to live to X being sick/disabled. We'll live just as long. The only question is - well, or not. Healthspan and lifespan are decoupled. Ultimately, it's another way of saying - healthy living will not be longer living, and it does not retard aging. To conquer aging we need some other intervention (other than just healthy living).

[mccoy]

Pls allow a few ruminations, which should be treated as such (no hard evidence or proof and corrections are welcome).

 

In the blue zones, exercise is one of the common factors which are believed to cause to increase longevity (to increase the ratio of centenarians in a population). This seems not to be true in lab animals but cannot be ruled out in free humans, as you rightly repeat. Other common factors include moderation in food intake (not necessarily CR) and high intake of phytochemicals, plus some motivational factors like a purpose in life and some stress relieving factors in a quasi tribe-like social structure. 

 

The above may just be what allows the expression of the longevity genes in those specific populations. If so, extreme longevity and good health would be uncorrelated (decoupled).

 

However we put it though, whatever slows down the wear and tear of organs and the senescence of cells should increase longevity, according to one's own genetic potential.

 

Of course if we speak of extreme longevity, beyond the 105 benchmark, then it may be reasonable to believe that genetic governs (but those genes must be usually expressed by a proper lifestyle). Below some other benchmark, it might be the dominion of environment. And in the middle both may govern.

 

Humans like Jeanne Calment are obviously, at least in the present time, sheer statistical outliers. They do not fit into the general conceptual framework, they are the product of genetic flukes, a random and extremely rare combination of genes. Probably some cellular repair mechanisms are highly expressed (mechanisms which Aubrey De Grey would like to mimick by artificial interventions, as far as I understood).

[Saul]

CR with AN extends healthspan and maximal lifespan in many mammalian species -- we already have enough data

to imply taht CRAN extends healthspan in humans.

 

Hopefully also maximal lifespan.

 

Rather than fatalistically assuming that "my lifespan is (almost) completely controlled by my genetic makeup --

so there's little that I can do about it" --

 

IMO, our best bet is to practice CRON, and perform some aerobic exersize, plus a small amount of selective strenghthening

exercizes.

 

-- Saul

[TomBAvoider]

Here's another cautionary note about exercise - at least for white men:

 

https://www.sciencedaily.com/releases/2017/10/171016144846.htm

 

"Physically active white men at high risk for plaque buildup in arteries"

 

"White men who exercise at high levels are 86 percent more likely than people who exercise at low levels to experience a buildup of plaque in the heart arteries by middle age, a new study suggests."

 

This applies to men who exercise 450 minutes a week or more (Dean P. territory - possibly Saul, though I'm not sure). This is not the first time we've seen results which seem to implicate frequent or intense exercise in deleterious lifespan contexts.

[mccoy]

I didn't read the original paper, it must be seen if and how they normalized for dietary regimen, usually active persons take the freedom to eat lots of junk food, believing that they easily burn the excess of calories and neglecting the qualitative side of the food they eat.

[Todd Allen]

In addition to junk food many engaging in rigorous exercise carb load with things sometimes promoted as healthy such as pasta, bread and fruit juices or things promoted as performance enhancing such as energy drinks and power gel, etc.  All of these can lead to spiking blood sugar, hyperinsulinemia and insulin resistance, dyslipidemia, inflammation and a whole cascade of problems which contribute to cardiovascular disease.

[TomBAvoider]

Except that this effect was only observed in white men - equivalent women exercisers and black men exercisers did not experience that effect. I highly doubt that women, or black men refrain from junk food  or carb loading. Nope. I don't think this is the explanation at all. 

[mccoy]

right, but...Did they provide a mechanistic hypothesis to why prolonged exercise appears to be detrimental to white males?

[TomBAvoider]

The speculation is along the lines of increased stress on the arteries, but from the point of view of those who are interested in how much to exercise in one's own life, it doesn't really matter what the explanation is, does it? I mean, if you are a white male, you don't care if it is because the devil is involved. All that we care is that the effect is real. Which is my whole point. If this were some isolated study, one could perhaps file it under "interesting, but outlier". As is however, there's a steady drumbeat, an undercurrent if you will, of suggestions in multiple studies of a U shaped effect - this is even mentioned in the link above:

 

"According to Laddu and study co-author Dr. Jamal Rana, similar population-based cohort studies on cumulate exercise dose have caused some controversy by showing U-shaped trends of association between physical activity and disease risk."

 

There are many such studies, including the Copenhagen jogger study. The trouble with many of these are that often the numbers for the extreme exercisers are not large enough to make make definitive statements, and we are left with suggestions. But if you have "suggestions" that keep happening study after study, you start to worry that there is some fire behind all that smoke. No proof as yet, mind you, but an awful lot of smoke - too much for my taste.

 

As so often, perhaps moderation wins again, even in exercise. What shocked me in many of these studies - certainly the Copenhagen one - is how relatively low the exercise amount was before it became detrimental... shockingly so, IMHO. Truly shocking. For example, joggin above a fairly slow pace was already a negative. Jogging more than 3 times a week was a negative. Jogging more than 140 minutes a week or so was a negative, and the benefits diminished after about 15 miles a week and went into reverse by the time you hit 20. Too often, too intensely, too long. By that measure, I exercise too much - I jog 4 times a week. I jog anywhere from 160-200 minutes a week. And I jog at a fairly brisk pace. Now, I never thought my exercise was particulary strenuous (judging by how I feel subjectively the effort is), but there you go - the numbers say otherwise. And the reverse is also shocking - apparently you derive almost all the health benefits of jogging or aerobic exercise with shockingly low numbers - once a week or twice a week and less than an  hour a week, and you got well over 80% of the benefits. You could say almost the reverse. It's not that exercise is healthy, but rather that being sedentary is unhealthy - that's an important nuance. Again - exercise is NOT healthy, being sedentary IS unhealthy. It just so happens that the best remedy to being sedentary is exercise - but just a bit, and after that you start losing again, to the point where some of the more extreme exercisers have almost no advantage over the couch potato.

 

Again, this is not settled science, but something to keep in mind. I certainly have dialed back a bit on my exercising. I am quite busy these days, and often cannot jog my usual 4 times a week (and only do it 3 times), but nowadays I don't fret over it, and allow that maybe that is actually to my benefit. YMMV. As usual, more studies will come out and hopefully shed more light... though judging by the mess nutritional science is, I don't get my hope up too high. I suspect there will be a ton of back and forth, and no 100% proof either way. That said, I am happy to spend a bit less time exercising and more time living

[mccoy]

Tomb, I fully understand all your perplexities, but by now I give secondary importance to scientific literature (unless it's about mere chemical analyses of foods).

I let my subjective belief govern, in a semi-automatic Bayiesian assessment of the issue(s). I decide, in a way which may sound arrogant, which weight to give to every single piece of scientific literature according to various factors. I don't need to convince anyone. I am the master of my own assessments and decisions.

 

By now my Bayiesian belief on the exercise issue is this:

• extreme exercise is very likely detrimental
• sedentary habits are very likely detrimental 
• light exercise is beneficial
• harder exercise can be very beneficial
• harder exercise can cause wear and tear of connective tissues and joints
• harder exercise can be detrimental in the presence of adverse CVD factors
• harder exercise can constitute a very beneficial hormetic stressor
• harder exercise is less beneficial or even detrimental in mature and old age

The above assessments may change when presented new evidence, and that's a part of the Bayiesian process. I introduced the evidence you cited within the likelyhood function, but the posterior (final) probabilistic function is sensitive to all evidence and most evidence indicates that a moderately hard exercise is good.

[TomBAvoider]

I understand, but the drawback to your methodology from an outsider's perspective is that it's hard to access for anyone other than you. You know what goes into your conclusions, nobody else does. That makes it hard to exchange info and arguments. From your perspective internally, I would assume that you'd be interested in the validity of your conclusions and methods of reaching them. From what I can gather of your approach and likely outcome, is that it's the entire reason why metastudies exist - and at least those are done with a great deal more rigor than is likely with a subjective "Baysian" approach. In other words, metastudies already attempt to do that - nihil novi sub sole. YMMV.

[mccoy]

TomB, metastudies actually pool together a set as large as possible of previous screened studies and analyze the whole superset of data so obtained. In a way yes, we can say they pool together the evidence so far accumulated.

Yet we know that even metastudies can suffer some biases inherent to previous studies or the pooled analysis itself.

 

Yet, teh conclusions drawn from the metastudy you cited are not so far away to our previous knowledge. In that, a golden balance seems to exist, which consitutes the bottom of the U-shaped hazard function. Now, where the flat part begins and ends, that is probably ruled by subjective factors, mainly individual, sometimes collective.

 

I may receive benefit from pretty strenuos, but not extreme exercise, whereas that might be detrimental to you. Rather than blindly following the results of the metanalysis, I would use it as a general indication to find my own location in the U curve, or rather to avoid the deleterious domains at the extremes.

 

Unfortunately I have not the time to go back and criticize all studies and the metastudy, and to criticize Dr. Greger's conclusions that we must exercise at least 90 minutes a day (although not necessarily strenuosly) and try to find out who's right.

 

the only thing which still is baffling me, is why male whites should be so sensitive to lots of exercise. Any physical metabolic, hormonal, constitutional reasons? In absence of reasonable theoretical hypothesis I might rightly believe that some concealed bias may be present in the study. At least, until a feasible explanation is offered, the probability that there is some bias is not smaller than the probability that white females and people of African descent really do not suffer strenuos exercise.

[TomBAvoider]

And here comes Al P. with another valuable paper. Can I just say how much I appreciate everything Al is doing? I am forever grateful for all his tireless efforts. THANK YOU AL!

 

So this one is yet another entry in the field of exercise as a predictor of health/lifespan.  It's hard to disentangle the chicken and eggness of it all. PMID: 29055404 (thanks to Al P.):

 

Chasing the top quartile of cross-sectional data: Is it possible with resistance training?
Buckner SL, Dankel SJ, Mouser JG, Mattocks KT, Jessee MB, Loenneke JP.
Med Hypotheses. 2017 Oct;108:63-68. doi: 10.1016/j.mehy.2017.08.009. Epub 2017 Aug 7.
PMID: 29055404
http://sci-hub.cc/10.1016/j.mehy.2017.08.009
Abstract
Resistance exercise is believed to be important for improving several biomarkers of health and contributing to decreased all-cause mortality. However, a careful examination of the literature reveals a growing body of cross-sectional studies finding stronger associations between strength independent of physical activity on these various outcomes and biomarkers (i.e., C - reactive protein, homocysteine, total cholesterol) of health. Considering that engagement in resistance type exercise is associated with an increase in strength, such cross-sectional data is often used to promote engagement in resistance training. When one examines the cross-sectional studies together with the experimental work, however, this relationship becomes less clear. For example, being in a higher tertile or quartile for grip strength may be associated with more favorable biomarkers or health outcomes, yet, experimental work shows that grip strength does not change with traditional resistance exercise. This seems to suggest that our interpretation and application of this literature may be incorrect. It is our opinion that much of the cross-sectional work may more accurately illustrate inherent differences between individuals who are "weak" and individuals who are "strong". In addition, there is conflicting experimental evidence and a lack of longitudinal support that resistance exercise may have a meaningful effect on long-term health outcomes. Using this evidence, we present our "human baseline hypothesis", which proposes that the baseline value of strength that a person possesses prior to training may be a more appropriate indicator regarding long-term health outcomes than the act of training itself.
 

So the conclusion here is that when we show that grip strength is a marker of health status, exercise can be a confounding element at best. Because what matters is what you grip strength is naturally, without exercise. If you have a weak grip, exercising to the point where you have a strong grip will not help you achieve the same benefit that naturally strong gripped people have without exercise. In other words, exercise does nothing for you in this respect. Which makes one question, yet again, the value of exercise to health/lifespan as opposed to what your genes have already determined about your health/lifespan.

 

The same for the other biomarkers mentioned (i.e., C - reactive protein, homocysteine, total cholesterol) - perhaps affecting those biomarkers through an intervention like exercise is merely affecting the biomarkers and distorting their predictive value vs health/lifespan? Perhaps in that case your biomarkers improve, but your health/lifespan does not. It's like going in with an eraser and pen on your test result - you can change an F to an A, but your knowledge will not improve even if your grade does. If you leave the grade where it is, without intervening with the eraser and pen, the grade will be an accurate predictor of your knowledge. Same here - if you exercise, it acts like exercise=eraser+pen, you will improve your biomarkers (grades), but your health/lifespan=knowledge will not improve. Or as some studies indicate, excessive exercise may actually harm your health/lifespan. Avoid being sedentary, but no more - perhaps.

[mikeccolella]

Nutrition/exercise research is junky to say the least. There are so many variables, confounders that unless you have very powerful stats like smokers have 20 times the lung cancer then non smokers its a guessing game. I see the merry go round and it just keeps on keeping on. Remember the fat is bad nutrition science? That caught on and people still beleive it. And who knows if it is or not?? The consensus now after all these years is that its great stuff so eat it. Most people will improve their lipids quite dramatically from eating more of it. I know mine improve with higher fat.

 

****** Keep in mind that if Blacks and woman are not having this effect then that is a red flag IMO because it dont make any sense physiologically and I would bet theres an association involved. White guys who run are different somehow in their behaviors.

[TomBAvoider]

Women are easy - there are many physiological differences between men and women, so that's not much of a stretch to say they *might* respond differently to strenuous exercise. With blacks vs whites, it is a bit more tricky, but not impossible - there are quite a few conditions which have drastically different risk profiles, some obvious and on the surface understandable, such as prevalence of skin cancer, and some not obvious. So white guys might have different behaviors, or it may be a real difference. Who knows. 

 

But what is interesting is what I brought up in another context, and that is marginal vs pronounced effect. There are very few studies that show any benefits to smoking tobacco (excepting things like Parkinson's). They're all in one direction. The effect is very clear and very pronounced: it's bad for you. Why don't we have the same findings on the effects of exercise? Why should there be so many studies showing ambivalent effects, a U curve, null or outright negative effects? Plainly exercise effects are not as clear-cut as smoking tobacco. If the effects are so weak (either way) should we spend so much time fussing over exercise either way? Or is it better to just do enough not to be sedentary (wheather that invovles some exercise or not). In other word, avoid sedentary behavior, but don't sweat exercise either way, and don't overdo it, as it ain't buying you anything except possibly trouble.

[mikeccolella]

I agree with your summary point Tom. We generally sweat over these things and if as you say the effects are marginal either way than simply be reasonable about including activity. Personally I totally enjoy incorporating purposeful activity into my daily routines. Last night for example I spent several hours organizing my garage while listening to music. A heck of a lot more satisfying/enjoyable than going to the gym and running on a treadmill. And best of all I accomplished 2 things at the same time!

[mccoy]

 

 

For example, being in a higher tertile or quartile for grip strength may be associated with more favorable biomarkers or health outcomes, yet, experimental work shows that grip strength does not change with traditional resistance exercise. 

 

To my knowledge, Deadlifts, pullups, curls, especially with today's large diameter applied grips, do contribute to grip strenght. Everything which implies a grip on handles or dumbbels or barbells would contribute. Doesn't that constitute traditional resistance exercise? What's traditional resistance exercise? Free-body squats? 

[mccoy]

The top strongman Eddie hall recently deadlifted 500 kg. Aside from the fact that the feat nearly killed him, I'm inclined to believe his grip strength has improved a tad by such resistance exercise. That's one of the most traditional among the resistance exercises. 

 

[Todd Allen]

A day of dining with Eddie Hall...

https://www.youtube.com/watch?v=YQEJyjKTH9g

[mccoy]

He's Brian Shaw actually, another renowned strongman pro and I enjoyed the vid!!

Eddie hall apparently has the 2017 strongest man title and still own the deadlift record undert strongman rules.

 

Those guys are simply immense, Brian shaw is 2.03 m, 192 kg that is 6'8", 423 lbs. He, Robert Oberst (2.03 m, 180 kg), and Hafbor Bjornsson (2.06 m, 180 kg) are the hugest among the huge ones. Eddie Hall is 1.91 m, 186 kg, the small brother in the family. 

 

What I liked best in Shaw's video is when he calls eating 'a necessary evil'.

 

Apparently those guys must be eating all the time to repair the damages the muscle tissues incur during their incredibly grueling workouts. Also, they all take steroids and the rules we know change. The Upper digestibility limit for proteins shifts upward by a significant value. Quantities higher than 2 g/kg/day are not excreted. Those guys easily eat one pound of protein per day.

[Todd Allen]

Oops, my bad.  The vid says up front it is Brian Shaw, but I was bouncing through a bunch of strongman vids and still had Eddie Hall on the brain.

 

Hopefully these guys are donating their bodies to medical science when they die.  It would be fascinating to know how their various organs:  liver, heart, kidneys, etc. cope with the strains.

[mccoy]

Todd, i too am fascinated by those monsters and when a young man tried to emulate them, not having the necessary strength though. I was more aestetically gifted, without the brute force.

 

I couldn't but buy Eddie hall's autbiography after watching his 500 kg lift. As a teen he was a competitive swimmer, then switched to bodybuilding and ecentually strongman competitions.

 

He describes his preparation to the 500 kg record and it's something really impressive to understate it. These guys apparently need bodyweight to increse their lifts, they need to continuosly indulge with food and max up their muscle and body mass, the only compromise being the necessary mobility to carry out some of the strongman tasks. Also, these guys are aware of the mental part of the job: focus, visualization and so on.

 

Bottom line, coming from the monster guys, strength is partly genetic but is acquired as well by strenuos practice. To return in topic with teh posted article, does the acquired (grip)strength contribute to longevity or only the genetic, no-training strength contributes as the article contends. The latter seems very illogical to me, whereas the former might be true until a certain point, the point where to max up grip strength metabolic and physical abuse becomes a necessity.