Resolving the Resistance Training Paradox

anti-aging program

resolving the resistance training paradox

The Resistance Training Paradox: Growth vs Longevity

A few weeks ago I wrote about what I called The Resistance Training Paradox, the paradox consisting of the fact that resistance training (weightlifting) promotes growth, and a necessary trade-off exists between growth and longevity. Exercise, however, is health- and longevity promoting. So how could resistance training both promote growth and aging and be a health-promoting exercise? One or the other must give. This post is about resolving the resistance training paradox.

I believe the answer is that resistance training does not in fact promote aging, and is health- and longevity-promoting. The explanation follows.

The hormone that is mainly responsible for growth, including growth of muscle tissue, is insulin-like growth factor 1, or IGF-1. Growth hormone itself (GH) appears to act by increasing the amount of IGF-1 in circulation.

IGF-1 promotes aging

IGF-1 definitely promotes aging. For example, humans who are genetically deficient in growth hormone receptors have “severe GHR and IGF-1 (insulin-like growth factor–1) deficiencies”, and the title of the article from which this quote comes is instructive: Growth Hormone Receptor Deficiency Is Associated with a Major Reduction in Pro-Aging Signaling, Cancer, and Diabetes in Humans. In mice, genetic deficiency of IGF-1 means longer life. A recent review by two stalwarts in anti-aging research, The key role of growth hormone–insulin–IGF-1 signaling in aging and cancer, states, “The life-prolonging effects of caloric restriction are likely related to decreasing IGF-1 levels.” And by the way, there are many, many studies linking IGF-1 to aging and its diseases; no cherry-picking of studies here, I’m not making this up.

So, calorie restriction, a known life-extender, appears to work by decreasing IGF-1 levels. IGF-1 in turn modulates autophagy, i.e. the more IGF-1, the less autophagic activity. We saw in a recent post here that autophagy is critical for the optimal anti-aging strategy.

IGF-1 promotes growth. So does resistance training. However, resistance training does not result in higher IGF-1 levels. In Hormonal Responses and Adaptations to Resistance Exercise and Training, the authors, again experts in this field, state that the IGF-1 response to resistance training is an acute one, and that resting concentrations remain normal. Another paper, Resistance training alters plasma myostatin but not IGF-1 in healthy men, reported on a study of volunteers who underwent 10 weeks of resistance training, and reported that “IGF-1 did not change from pre- to post-training”. Myostatin, however, did decrease substantially, which presumably accounts for muscle growth. Conclusion:

Myostatin may play a role in exercise-induced increases in muscle size, its circulating levels decreasing with resistance training in healthy men. Exercise of the whole body versus the elbow flexors alone did not provide a supplementary stimulus in altering resting plasma IGF-1 or myostatin, or in increasing muscle strength or size. Thus, by default, growth factor responses local to the muscle may be more important than circulating factors in contributing to muscle hypertrophy with resistance training.

Resistance training does not increase circulating levels of IGF-1, except perhaps acutely, within an hour or two after the workout. Therefore resistance training does not promote aging.

But, we’re still left with the growth-longevity trade-off, and there is something peripheral to resistance training that does appear to promote aging, and that is high protein. I’ll have more to say about this in a future post.

Further reading

The insulin/IGF-1 signaling in mammals and its relevance to human longevity
‘Anti-Aging’ Hormone May Actually Shorten Life
The paradox of the insulin/IGF-1 signaling pathway in longevity.
Protein and amino acid restriction, aging and disease: from yeast to humans
Long-term effects of calorie or protein restriction on serum IGF-1 and IGFBP-3 concentration in humans
Chronic resistance training activates autophagy and reduces apoptosis of muscle cells by modulating IGF-1 and its receptors, Akt/mTOR and Akt/FOXO3a signaling in aged rats
GDF11/Myostatin and aging. This article actually may make a case against resistance training.
Prolonged Fasting Reduces IGF-1/PKA to Promote Hematopoietic-Stem-Cell-Based Regeneration and Reverse Immunosuppression

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15 comments
Don says January 22, 2015

Great info. My take is that strength training definitely slows aging. I am very close to my brother in a lot of ways, looks, voice etc however I have been doing weights for the last 8 years and he has not. Now although he is 4 years older than me, he looks more like 10 years older. Grey hair, balding etc. I have yet to get any serious grey and have kept all mine. Keep up the great work!

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Derek Wolf says January 23, 2015

Great article.

Thanks for sharing your finds regarding IGF.

It seemed fishy that strength training —> aging in the sense that many limp wristed health bloggers insist. It is counter intuitive and goes against my instincts. Expressing great genetic expression as a man, via weight lifting = poorer health? Doesn’t make sense.

In fact I felt so strongly about this that I had previous decided, “Forget what those limp wrists theorize, I’ll continue training til I’m 80+ and show them that it only benefited me through my years!”

Thankfully there appears to be scientific study that shows there have been misconceptions, or misunderstandings about the IGF connection.

I’ll have to check back when you pick up with the protein connection. Matters of digestion/diet –> aging much more relevant IMO than weight-training –> aging. Especially in regards to eating 300+ grams protein a day, 6 meals a day, constantly bombarding the digestive system vs a Intermittent Fasting type protocol.

Appreciated, be well.

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    P. D. Mangan says January 23, 2015

    Thanks, Derek. I, too, will be weight training as long as I possibly can. And I do agree that diet is way more important to aging than just about anything else.

    Reply
duderino says January 25, 2015

How much protein is “high” protein? Reading the abstract of”Long-term effects of calorie or protein restriction on serum IGF-1 and IGFBP-3 concentration in humans” paper, I came across this line:

Reducing protein intake from an average of 1.67 g kg−1 of body weight per day to 0.95 g kg−1 of body weight per day for 3 weeks in six volunteers practicing CR resulted in a reduction in serum IGF-1 from 194 ng mL−1 to 152 ng mL−1

It follows to me from reading the abstract, that although a floor for the benefits of dropping protein isn’t mentioned, since extreme calorie restriction wasn’t effective, the extremely low protein intake shouldn’t be effective either (It was locked in at 16% of energy across the board).

If my napkin math is correct, you would divide the .95 “reduced” amount of protein by 2.2046 to convert to pounds. So roughly .43 grams per pound to reduce the IGF1 per the study. Or for a 180 pound man like me, about 1 Chicken burrito from chipotle.

There could be some sweet spot, Where one could A) Get just enough protein to build muscle and B) Get near the floor of where reducing protein reduces aging related to IGF1. Maybe .6 per pound? Or maybe their truly is a trade off.

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    P. D. Mangan says January 25, 2015

    Excellent question, duderino. As it happens, the RDA for protein is 0.8 g/kg of lean body weight, less than the .95 cited in the study as lowering the level of IGF-1. The amount of protein the calorie restriction folks were eating before, 1.67 g/kg, is in bodybuilder territory. The RDA of 0.8 is not set in stone, of course, and plenty of people including me have criticized it as too low. The amount that bodybuilders can benefit from has a ceiling right around 1.6 to 1.8 g/kg, and I suspect that might be a bit lower, since a couple SDs were added to ensure that everyone was covered.

    To get to my point, there very well might be some kind of sweet spot for protein consumption: enough for strength athletes yet not too much to promote aging. However, given that the calorie restricters dropped their IGF-1 ~25% with 3 weeks of less protein – which was still more than the RDA – we still don’t know what the best level of IGF-1 for anti-aging purposes is. Presumably the lower the better, but I don’t know. I don’t know if the level of CR in lab animals has ever been correlated with level of IGF-1, and even if it had, it wouldn’t help us much, since we need human data; in turn, the human data can’t be correlated with aging since we don’t have data on the degree that IGF-1 levels correlate with lifespan. So it seems like a lot of guesswork.

    But, to repeat, the CR people who lowered their IGF-1 did eat what looks like a fair amount of protein. It was not radically restricted.

    PS: A study by Barzilai found “females with IGF-1 levels below the median (≤ 96 ng mL−1) had significantly longer survival compared with females with levels above the median, P < 0.01. However, this survival advantage was not observed in males (P = 0.83)." http://onlinelibrary.wiley.com/doi/10.1111/acel.12213/full

    At this point I don’t know whether female IGF-1 levels are naturally lower than male. Quite possibly. In the CR study, IGF-1 levels were reduced to 152, considerably higher than the level just cited for older women.

    Reply
Optimizing protein intake - Rogue Health and Fitness says March 17, 2015

[…] The means by which protein restriction causes the longevity promoting effects of calorie restriction seems largely due to a decrease in levels of insulin and IGF-1, which promote growth of all kinds, including cancer. People who are deficient in IGF-1 have a very low incidence of diabetes and cancer. […]

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Weightlifting will extend your lifespan - Rogue Health and Fitness says March 29, 2015

[…] the new study on mice, the longest lived mice had 30% less myostatin than controls. In humans, a 10-week program of resistance training decreased myostatin levels an average of 20%, although the individual range was from +5.9% to -56.9%. Importantly, IGF-1 levels did not […]

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ProudDaddy says September 9, 2015

I meant to tell you about this when I had the reference in hand, but life got in the way. Anyway, the study showed something to the effect that IGF-1 is beneficial/detremental depending on where it is found. Concentrations in muscle were found to be good (for longevity). I think it was serum concentrations that were bad.

If you are interested, I think I might be able to refind the reference.

Regards

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    P. D. Mangan says September 9, 2015

    Proud Daddy, I would like to read that if you can find it. Funny, I was just going over this post again today, and I found a study yesterday that showed that lifting lowers systemic IGF-1, but likely increases it inside the muscle. That agrees with what you say here.

    Reply
      posthasty says September 9, 2015

      I think insulin resistance/hyperinsulinemia is a more pressing concern than fretting too much over IGF-1 levels.

      Horm Metab Res. 2015 Sep 8. [Epub ahead of print]
      Bioavailable IGF-1 and its Relation to the Metabolic Syndrome in a Bi-Ethnic Population of Men and Women.
      Koegelenberg AS1, Schutte R1, Smith W1, Schutte AE1.
      Author information:

      1 Hypertension in Africa Research Team (HART), North-West University, Potchefstroom, South Africa.

      Abstract
      Insulin-like growth factor 1 (IGF-1), an insulin sensitivity and vasculoprotective factor, associates negatively with the metabolic syndrome. However, IGF-1 is reduced by factors such as inflammation, oxidative stress and liver dysfunction. We investigated the relationship between bioavailable IGF-1 and the number of metabolic syndrome components and determined whether this relationship is independent of inflammation, oxidative stress and gamma glutamyl transferase (γ-GT; a marker of liver dysfunction). This study included 907 black and white participants stratified by sex (aged 43.0±11.8 years). Among them 63 participants had fasting glucose levels of ≥+7.0+mmol/l and/or used diabetes medication. Via standard methods we determined waist circumference, fasting glucose, triglycerides, high-density lipoprotein cholesterol and blood pressure. We also determined high-sensitivity C-reactive protein (CRP), reactive oxygen species (ROS), γ-GT, IGF-1 and insulin-like growth factor binding protein 3 (IGFBP-3). IGF-1/IGFBP-3 was used as an estimate of bioavailable IGF-1. Total IGF-1 was similar between men and women (p=0.10), however, bioavailable IGF-1 was lower in women (p<0.001). In multivariate-adjusted analyses, IGF-1/IGFBP-3 was inversely associated with the number of metabolic syndrome components in both sexes (men: β=- 0.11; p=0.013 and women: β=- 0.17; p=0.003). Upon inclusion of ROS, γ-GT and CRP, significance was lost. In patients without diabetes, the results for men changed marginally, but were consistent for women. We found an inverse association between bioavailable IGF-1 and the number of metabolic syndrome components. But the relationship was dependent on oxidative stress, liver dysfunction and inflammation, suggesting underlying processes by which the metabolic syndrome attenuates IGF-1.

      2. Horm Res Paediatr. 2015 Sep 9. [Epub ahead of print]

      Reply
        P. D. Mangan says September 9, 2015

        Interesting, thanks for that. Lifting of course also lowers insulin levels and improves insulin sensitivity.

        Reply
      ProudDaddy says September 9, 2015

      This 74-year-old brain thinks the article might have been Sonntag, et al. “Diverse Roles of Growth Hormone and Insulin-Like Growth Factor-1 in Mammalian Aging: Progress and Controversies”. Journal of Gerontology (2012). A section starting on page 6 discusses expression in different tissues and the following section discusses beneficial effects of GH/IGF-1 late in life.

      I have to give credit to Josh Mittledorf for discovery of this paper.

      Reply
        P. D. Mangan says September 9, 2015

        Thanks!

        Reply
        P. D. Mangan says September 11, 2015

        It’s odd, but Josh Mitteldorf apparently won’t approve my comments at his site. I posted a polite notice of an error of his – in his most recent post, he referred to HGH and IGF-1 as “steroid hormones”, which they are not, they are protein hormones. I posted that several days ago and as of now it is not there. Neither did he approve my other comment where I said that I believed a lot of confirmation bias was going into the study of growth hormones as pro-aging. (For one thing, it makes veganism appear to be a good diet.) Calorie restriction also substantially inhibits the accumulation of iron, and that seems to be barely studied at all in aging research. Seems important to me.

        I don’t know if he won’t allow links to this blog or he just doesn’t want anyone to know he made an mistake in basic biochemistry. He always seemed fair and relatively easy-going but I must admit to being irritated at this.

        Reply
Calorie Restriction and Intermittent Fasting: Is There Any Difference? - Rogue Health and Fitness says November 19, 2016

[…] Scientists have long researched and debated the mechanistic cause of the effects of calorie restriction (CR) on lifespan. The most common idea is that it reduces insulin and IGF-1 signaling, as well as mTOR activation, and that this sends the animal’s physiology into extended longevity mode. Insulin and the others are growth signals, so if this is true it agrees well with the idea that there’s a growth vs longevity trade-off. […]

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