The Resistance Training Paradox

deadlift

Is this man promoting the aging of his body?

In a recent post, Intermittent fasting and the growth-longevity tradeoff, noting the link between growth and aging and how the biochemical sensor mTOR appears to be the nexus between the two, I wrote:

What else activates mTOR? You guessed it, resistance training: Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo. Sad but true: all of us muscle heads may be promoting the aging of our bodies by lifting and eating protein. There is something of a paradox here, namely that exercise is a healthy activity, and resistance training is no exception. The paradox can perhaps be resolved by noting that exercise will help you live healthily for your three score and ten – or whatever it is now, 81 or something – but if you want to have a shot at being a centenarian, perhaps not.

That was, is, my attempt to grapple with what looks like a paradox, namely, that exercise has been shown to be a very healthful activity and likely prolongs life, but resistance exercise, which also appears to be no less healthy and maybe more so than other forms of exercise, causes muscle growth and hence may promote aging.

I titled a recent post Weightlifting slows aging. In that post, the emphasis was on the fact that resistance training combats sarcopenia (loss of muscle mass) in older people. Sarcopenia is a serious condition that affects many elderly people, so weightlifting can be a strategy that keeps them in good health and may help them literally avoid death. At least for as long as any of us can, which isn’t indefinitely.

So how can resistance training be both healthy and a promoter of aging at the same time? It can’t.

Weightlifting (resistance training) does promote an increase in mTOR. Rats respond to an exercise similar to resistance training with an immediate increase in mTOR, and that’s why muscles grow.

Collectively, these results provide strong evidence that mTOR-mediating signalling is transiently upregulated during the immediate period following resistance exercise and this response may constitute the most proximal growth response of the cell.

mTOR is also “a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo“.

So, resistance exercise causes an activation of the mTOR pathway, and this increase is central to muscle hypertrophy.

What evidence is there that mTOR is involved in aging? In the worm C. elegans, one of the most widely used animals for the study of aging, deficiency of TOR (the non-mammalian equivalent of mTOR), doubles lifespan. Inhibition of TOR in Drosophila increases lifespan. In mammals (mice in this case), blunting IGF-1 signaling increases lifespan, and IGF-1 activates mTOR.

The illustration below shows the relation between IGF-1, mTOR, leucine, and muscle protein synthesis.


Mice that have had their IGF-1 receptors partially knocked out live up to 33% longer than controls: IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice.

From a review, The key role of growth hormone–insulin–IGF-1 signaling in aging and cancer:

Studies in mammals have led to the suggestion that hyperglycemia and hyperinsulinemia are important factors in aging. GH/Insulin/insulin-like growth factor-1 (IGF-1) signaling molecules that have been linked to longevity include daf-2 and InR and their homologues in mammals, and inactivation of the corresponding genes increases lifespan in nematodes, fruit flies and mice. The life-prolonging effects of caloric restriction are likely related to decreasing IGF-1 levels. Evidence has emerged that antidiabetic drugs are promising candidates for both lifespan extension and prevention of cancer. Thus, antidiabetic drugs postpone spontaneous carcinogenesis in mice and rats, as well as chemical and radiation carcinogenesis in mice, rats and hamsters. Furthermore, metformin seems to decrease the risk for cancer in diabetic patients.

Furthermore, mTOR, which is an acronym for mammalian target of rapamycin, was discovered when investigating the effects of the drug rapamycin, an immunosuppressant. It turns out that rapamycin slows aging in mice and makes them live longer. Metformin is an anti-diabetic drug, and it too extends lifespan in mice, potently inhibits cancer proliferation, and inhibits mTOR. I’ve heard anecdotes that bodybuilders used to use metformin to cut fat, and in fact metformin is sometimes prescribed as a weight loss drug, but the bros stopped using it because it not only cuts fat, it cuts gains; this makes sense since it inhibits mTOR. This is another piece of evidence for the growth-longevity Trade-off, since metformin both cuts gains and extends life.

The branched-chain amino acid leucine is a key regulator of muscle protein synthesis, and since weightlifters like to eat lots of protein, they will be getting lots of leucine, especially if they use leucine-rich foods like whey. And leucine also activates mTOR. However, there’s a paradox within a paradox here, in that BCAAs can extend lifespan in mice: Branched-Chain Amino Acid Supplementation Promotes Survival and Supports Cardiac and Skeletal Muscle Mitochondrial Biogenesis in Middle-Aged Mice. So if someone has a high protein intake, with a concomitant high leucine intake, maybe it’s a wash as far as aging goes.

I hope I’ve given the reader enough evidence here to show that there is a resistance training paradox. I tend toward the view that resistance training is completely healthful and that the paradox lies somewhere in the mTOR view of aging. But I can’t say that I know that, or if anyone knows that. It’s a paradox that needs resolution.

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9 comments
Pete says December 8, 2014

It seems logical that there’s a healthy middle ground. There are diminishing returns on physiological benefits of strength training, just like endurance training. A little baseline cardio seems to do wonders for health, but then you hear about big time ex triathletes dropping dead from heart problems or something else. Same deal with the 300 pound bodybuilding mass monsters who are dropping dead before 50.

Baseline strength is a huge component of quality of life. I cringe at the thought of becoming totally weak and decrepit in my senior years, having to muster maximum effort to do basic things like get out of my chair.

But, will my life be that much better or healthier if I can deadlift 500 pounds as opposed to 400 pounds? Not really, to be perfectly honest. I’m 28, and I have an idea of what I want my baseline strength and body composition to be. Then my goal is figure out and do the minimum required to maintain it.

Jimmies get rustled when people talk about how more is not always better, and can be worse. But it’s an important topic that deserves honest discussion for sure

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George Ironthumb says December 8, 2014

Dude,, if I was given a choice to become a centenarian and look like a eunuch or to die at 81 and look like the person that I am, veins popping out even from the casket then I choose the later.

These researches can indeed show these results but we have more evidence that lifters and active people have longer lifespan, nonetheless.

Thank you for this very interesting article by the way, I will watch out for more!

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    P. D. Mangan says December 9, 2014

    George, I think I would make the same choice. In any case, that’s the choice I’m making now, living it. Good to see you over here.

    Reply
Jason says December 9, 2014

This stuff is fascinating. I’ve read that people who use non-US producted HGH test to see if it’s bunk by looking at IGF-1, which is elevated by HGH. As HGH becomes more popular as an anti-aging drug (look at Hollywood and Stallone especially) I wonder if it will cause shorter lifespans by reducing autophagy and keeping the body in “grow” mode with the risk that entails.

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    P. D. Mangan says December 9, 2014

    Jason, glad you find it interesting. Sometimes I write these things and wonder how interesting others will find it, so that’s good to know. As for HGH, I don’t know that taking it earlier in life as Stallone did will compromise lifespan, but in older men it seems a bad idea, and most doctors agree with that. It causes growth in everything, presumably including tumors.

    Reply
      Jason says December 9, 2014

      Well, I also enjoy getting bloodwork done because I think how the body operates is fascinating so I’m certainly not the mainstream. With regards to HGH, Stallone is on it now ( and almost certainly TRT) and it’s pretty popular for anti-aging in Hollywood. there was a Vanity Fair article on it a few years back, I believe. Jennifer Aniston is probably also on it, though she hasn’t confirmed it like Sly who is pretty open in advocating for it. I agree with you about the tumors and elevated cancer risk. As it continues to be prescribed for anti-aging I’ll be curious to see follow-up studies that connect it to earlier morbidity.

      Reply
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