Why Stress and Recovery Are Essential for Long Life

Stress and recovery are essential for long life and good health. While we usually think of “stress” as something bad, that really only applies to chronic stress. Certain acute stresses lead to better health and life extension.

No stress and too much comfort shorten life.

The rhythm of stress and recovery

The graph below (which I made) shows a natural daily rhythm that the body cycles through.

 

This rhythm is largely driven by food and by fasting.

When we eat, insulin increases, which leads to mTOR activation and anabolism.

A feature of muscle that most don’t realize is that it constantly builds up and breaks down, and this is normal and desirable.

Eat protein and other nutrients, and muscle protein synthesis increases. When fasting, muscle breaks down to supply necessary amino acids to the rest of the body. Leucine, a BCAA, is the master regulator of synthesis.

mTOR is a nutrient-sensing cellular mechanism that promotes both growth and aging.

A prominent theory of aging (that of Mikhail Blagosklonny) holds that over-activation of mTOR is the primary driver of aging.

Yet mTOR is also necessary for good health. What seems to be happening in aging is chronic over-activation, not sporadic activation. Although it is certainly possible that any activation of mTOR promotes aging in some manner.

When fasting, the absence of nutrients decreases insulin, de-activates mTOR, and promotes autophagy, the cellular self-cleansing process that rids our cells of junk and keeps them youthful. A build-up of cellular junk occurs in aging due to decreased autophagy as well as the accumulation of non-degradable lipofuscin, leading to the “garbage catastrophe of aging”.

Aging flattens the wave

Besides eating and fasting, longer term processes affect the shape of the sine wave above.

Aging is perhaps the most important.

As we get older, the daily rhythm starts to look like the one below, flatter than when youthful.

 

The peaks are lower, so muscle protein synthesis doesn’t happen at the same rate as previously, when young.

That leads to the muscle loss seen in aging.

The valleys are higher, so autophagy is not induced at as high a rate as when young. That leads to accumulation of cellular junk, which in turn leads to poor cell function and the susceptibility to illness and breakdown that virtually defines the process of aging.

Insulin becomes chronically higher in aging, which in turn activates mTOR and promotes even more aging in a vicious cycle.

The graph below (source) shows how these factors interrelate. Insulin activates mTOR, which inhibits autophagy. (This makes perfect sense, since when you take in nutrients, you want to build, not break down.)

The importance of stress and recovery

Interventions that stress the body generally lead to deactivation of mTOR, lower insulin, catabolism, and increased autophagy.

Interventions that allow recovery generally lead to activation of mTOR, increased insulin, anabolism, and decreased autophagy.

Both are necessary.

But in the modern world, recovery and comfort dominate.

If we are always eating and resting, we never apply the necessary stress to our bodies.

Consequently, without stress, it deteriorates.

Obesity soundly represses autophagy and therefore activates mTOR and promotes aging. Or as I like to say, obesity is an archetype of aging.

It’s an open question how much of aging is just people letting themselves go. Certainly, animals age, and while aging is intrinsic to almost every organism, a decline in physical function leads to more aging in a cycle of reinforcement.

For example, mainstream thinking has it that insulin resistance increases with age, and that it’s closely connected to aging. Yet when abdominal fat is controlled for, aging explains only a small fraction of the variance in insulin sensitivity.

These results suggest that insulin resistance is more closely associated with abdominal adiposity than with age.

Therefore, you can fight aging by maintaining good insulin sensitivity. (Article coming soon on this.)

To our point here, how much of aging is due to too much comfort and not enough stress?

It seems to be a given that as people age, they feel they “deserve” their comfort and lack of exertion. (Not to mention lack of ambition.) Psychological feelings of entitlement (for lack of a better word) could accelerate aging in this manner.

If we stress ourselves often, allowing for full recovery, we have a means of counteracting aging.

How to stress and recover

The means of stress are many and have been discussed on this site many times.

  • Exercise. Resistance training and HIIT are the most effective for both activating stress response mechanisms as well as ramping up muscle anabolism.
  • Intermittent fasting. By going without food, we decrease insulin and mTOR activation, and increase autophagy. This stress helps keep cells in fine tune and facilitates the proper working of our physiology.
  • Other stresses include cold showers, sauna bathing, solar radiation, AMPK activators like metformin and resveratrol, other phytochemicals such as in tea and coffee. Even occasional loss of sleep can cause a beneficial stress, relieving depression.

The means of recovery:

  • Food. Eating puts us into recovery and anabolic mode. Quality of food is important, such as adequate protein.
  • Sleep and rest.

In our modern world, the emphasis is on recovery. We eat constantly and never get into a properly fasted state, then we sit on our backsides watching Netflix.

Too much stress is harmful of course, since the principle of hormesis requires a low-dose of a stress or toxin. Too much exercise, too much cold exposure, etc, can be harmful. However, those limits are reached by few.

Some form of stress should be practiced daily, in my opinion.


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Leave a Comment:

25 comments
Stefan Sladeček says August 21, 2018

Great article, as always.

Allow me to sharpen just one single point: It’s not so much the flattening of the sine wave per se which leads to muscle loss in the elderly (since the flattening also means less catabolism, not only less anabolism).

It’s more the negative effects of lower ambition, lower exercise, lower T, lower insulin sensitivity which cause that the troughs are lower than the peaks are high.

Reply
    P. D. Mangan says August 21, 2018

    Thanks, Stefan, that’s true. More oxidative stress and inflammation seems to be a factor in muscle loss too.

    Reply
Herman Rutner says August 21, 2018

Hi PD,
I read a recent report on medical monitoring studies done on several Irish prisoners who fasted to death in about 80 days. These prisoners had lost all of their body fat but only about 6% of their muscle tissue contrary to your claim of muscle catabolism in brief fasts. Their inactivity may been a factor in low loss of muscle mass.

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Dave says August 22, 2018

Thanks for the article PD.
On the mTOR portion of article, I wanted to share these 2 recent podcasts with other folks that may find the latest research into mTOR interesting. They are technical, but I found them interesting and support the overall thesis of PD’s article.
https://peterattiamd.com/mattkaeberlein/
https://peterattiamd.com/davidsabatini/

Reply
    P. D. Mangan says August 22, 2018

    Thanks, Dave.

    Reply
    Paul rivas says August 24, 2018

    Thanks Dave

    Those podcasts were very informative

    Reply
paul rivas md says August 23, 2018

Well done!

I thought that I would update everyone on the status of my associate Eli who has now been on a rib eye steak only diet for the past several months. A very detailed and comprehensive lab test revealed the following:

T chol 531 LDL 383 TRiglycerides 46 HDL 103
CRP hs 0.8 ( <1.0)
Insulin 1.0

On first glance this may look pretty good especially since the Tri/HDL ratio is outstanding as is the insulin level and CRP ( low inflammation). But other tests showed:

sdLDL 38 (<21)
LDL-P 3500 ( <1000)
small ldl particle 922 ( <500)
Apo B 298 ( <80)
Lpa 114 (<75)
Lp PLA 268 ( <196)
myeloperoxidase 314

What all of that means is that he has a very high percentage of small density ldl particles, high APO-b and Lpa ( both of which are highly atherogenic), and while his CRP is good, the more specific markers of vascular inflammation , Lp-PLA and myeloperoxidase are both elevated.

On another note his omega 3 index is excellent but ferritin is high at 141 as is albumin at 5.1.

There are obviously very good numbers here but others that are quite concerning and are only apparent with detailed testing. It will be interesting to see how this evolves.

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    Rob H. says August 23, 2018

    Hi Paul, many thanks for the update – very interesting indeed! Quite a polarised result – and quite difficult to conclude whether it is ‘good’ or ‘bad’ overall. I know that both Dr Shawn Baker and Dave Feldman (‘The cholesterol code’) are collecting test data from people so why don’t you get in touch with these guys to add to the their ‘n=many’ studies?

    Reply
      Rob H. says August 23, 2018

      Although , just for what it’s worth- in my (very humble) opinion I think if Eli were to tweak his approach and add in a load of non-starchy veg and even some fruit (particularly before and after resistance training), plenty of dairy, eggs and fatty fish/ seafood he could significantly improve his atherogenic risk factors. Maybe with some 16/8 IF fasting thrown in too. At least I hope so – because that’s the approach I’m following!

      Reply
      Paul rivas says August 23, 2018

      One thing that I found very interesting was vascular inflammation in the presence of a good CRP. I also think that it’s amazing how dramatically an entire lipid profile can change after only a few months.

      Reply
        Diarmuid says August 24, 2018

        Hi Paul
        It would be interesting to know his GGT level (gamma glutamyl transferase) as a marker of oxidative stress / glutathione levels. Spectra cell run an intra cellular glutathione test which would give the most accurate assessment as to GSH status. GSH is a standalone marker for coronary heart disease and is further upstream than the blood markers you have listed (IMHO)

        Reply
          Paul rivas says August 24, 2018

          I know that his GGT is normal range

          Reply
          Ole says August 24, 2018

          Also his baseline numbers (before starting the rib-eye only diet) would be of great interest.

          Reply
          paul rivas md says August 25, 2018

          Hi Ole
          Prior to this his numbers were quite different. His T cholesterol was 180 and LDL < 100. Hdl was 80 as were his triglycerides. That was on a strict fasting diet with low sugar and starch.
          His values have markedly changed in just a few months

          Reply
          paul rivas md says August 25, 2018

          Also important to note that only 10 to 20 % of people will react to high saturated fats with hyper production of LDL particles, and this not from studies but via anecdotal observations. This group should switch over to monosaturated fats.

          Reply
Jer says August 24, 2018

Hi PD
Have you seen the latest?… any booze is dangerous.
.looking forward to you spotting how they have been “fooled by randomness”. It is getting big coverage as you’d expect

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)31310-2/fulltext

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    P. D. Mangan says August 24, 2018

    Thanks, Jer, it’s the talk of the day on twitter, and of course I’m not buying it. I will try to write something about it.

    Reply
    Paul Rivas says August 24, 2018

    They identified 23 “ health problems” and found that over the course of a year 914 non drinkers developed one of these problems, whereas 918 of those who consumed one drink per day did so. And this was out of 100,000 people! So 4 more people out of a 100,000 per year at risk of “ health problems “. And this is what all of the fuss is about. The authors stated that this is an issue that must be addressed urgently . Prohibition?

    Reply
Joe Y says August 24, 2018

I hate to be morbid, but I recently read “Unbroken” — terrific read by the way — about Louis Zamperini, who was starved almost to death (among other things) by the Japanese, but lived to be over 97. I wonder if there are any studies about people who have gone long-term near-starvation, and how it affected their longevity. Again, my apologies.

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    P. D. Mangan says August 24, 2018

    I recently read about the Minnesota Starvation Experiment, the volunteers of which were conscientious objectors in WW2. Apparently many more of them lived past age 80 than would be expected by chance, some 50%.

    Reply
      Paul Rivas says August 24, 2018

      It is also well known that male concentration camp survivors who were subjected to severe periods of starvation in their twenties have almost universally experienced rather extreme longevity.

      Reply
Montgomery says August 28, 2018

(Off-topic)

Resting heart rate vs. BMI, biggest ever dataset;
indicates optimal BMI is indeed lower than widely thought.

https://twitter.com/Pogue/status/1034097546145222656

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James says August 29, 2018

Great article. But in order to draw practical applications in terms of health and longevity, more info is needed. How long goes it take to ‘switch off’ mTOR? Hours? Days?

Indeed, is mTOR like an on/off switch (either its on or its off) or is mTOR activity more like a continuum (from, say, high activity to low/zero activity)?

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    P. D. Mangan says August 29, 2018

    Hi James – mTOR is more of a continuum than an on/off switch. As for how long it takes to deactivate, probably not long, just as for insulin. Fasting, for instance, should deactivate mTOR quickly. And, like insulin, the problem with mTOR and aging is not activation but chronic overactivation. That’s how I see it.

    Reply
James says August 29, 2018

Thanks for your reply. Your parallel between insulin sensitivity and mTOR sensitivity is illuminating (and, indeed, suggestive; some people (i.e. diabetics) have impaired insulin sensitivity; might some people also have impaired mTOR sensitivity?). If mTOR is as sensitive as insulin, then IF should have significant autophagy effects (I’ve often wondered whether a daily intermittent fast of 16 hours is sufficient to trigger autophagy; if mTOR is as sensitive as insulin, it should).

More broadly, loving your work. Been following since the end of 2015, when I started donating blood to reduce body iron stores. Visibility takes time, but your work is graining traction, as evidenced by Taleb’s recent retweets.

Reply
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