Lifting weights "too much" might increase risk of death -- could rapamycin help?

So here’s something that’s been bothering me for quite a while, ever since I read this article: https://www.strongerbyscience.com/research-spotlight-lifting-longevity/

It appears that, from a correlational perspective at least, peoples’ risk of death actually starts going up – relative to doing nothing – if they lift weights for more than about 2.5 hours/week. Not just one study found this, either; it appears multiple studies have confirmed this J-shaped correlation between resistance training and mortality, with benefits plateauing at around an hour a week, and risk of death starting to go above baseline after a certain amount above that.

When I first read this, I had no idea what was going on. Neither, it appeared, do any of the researchers involved in these studies. I have yet to find a really plausible mechanism suggested for why this might happen. (Increased arterial stiffness and excessive inflammation are 2 possible candidates, but I’m not convinced.) After a lot of thought, though, one plausible candidate occurred to me: mTOR.

It’s pretty well established that lifting weights, and especially in conjunction with consuming protein, are strong upregulators of the mTOR pathway. So, I am wondering: could lifting weights a lot be upregulating mTOR sufficiently to actually be net pro-aging? Resistance training has many documented benefits (increased insulin sensitivity, reduced risk of falls and fractures), but I can’t help but wonder if the cons of frequent mTOR upregulation may begin to outweigh pros after a certain point.

If my idea is correct – maybe taking rapamycin could be a way to counteract this problem? I happen to like lifting weights regularly and like to see a fair bit of muscle on my otherwise skinny frame. I’d love to think we can have the best of both worlds – be strong and muscular, and live to be 100+. Or maybe things like intermittent fasting + light cardio (like brisk walks) on rest days could also help.

Would love to hear others’ thoughts on all of this, especially those of you who also lift weights regularly. I figured this might be the best place to get insights on all of this since mTOR is surely forefront on the minds of many people on this forum.

6 Likes

It may not be the training that reduces longevity. Bodybuilders and powerlifters eat a lot. Eating 7000 calories a day is not great for longevity, even though the training prevents obesity.

5 Likes

I have come across these myself, but I am not at all convinced about the causality. But if we play with the idea, is the total time decisive, or is it the number of workouts per week? 2 x 1.5 = 3h vs 3 x 1h. You would think that with the latter, mTOR activation would happen more often per week.

2 Likes

At my gym, there are not any old (by that, I mean 80+ years) bodybuilders.
Competition bodybuilders typically don’t live that long. I don’t know if it is because of too much lifting or steroid use.

6 Likes

Time in the gym is a poor metric. I don’t know what a correlation with time in gym would mean. It correlates more with having or not having other things to do, I’d guess.

Getting fitter (cardio) and stronger (weightlifting) is going to be health promoting. Recover well. Eat healthy etc.

6 Likes

The dose-response meta-regressions suggest that ~30-60 minutes of resistance training per week is associated with the largest risk reduction for all-cause mortality, cardiovascular disease incidence, and cancer rates (Figure 2). Furthermore, for these three outcomes, there appear to be no risk reductions (and possible increases in risk) for individuals performing more than 130-140 minutes of resistance training per week.

What counts as a “minute of exercise”?

Looking at my own program, each day might be 3-5 warmup sets, then 5-8 work sets. If only “time under the bar” actually doing the exercise counts, and each set takes a minute (probably a slight exaggeration) then I do 8 to 13 minutes a day or 40 to 65 minutes a week. Often I do assistance exercises as well but let’s leave that aside.

But if total time in the gym is counted then my resistance training takes a lot longer. There is at least a few minutes of rest between sets, plus time to switch plates, drink water, maybe go to the bathroom. That might add up to an hour a day or 300 minutes a week.

Let’s assume it’s only time under the bar, in which case I’m “in the healthy zone” of 30-60 minutes a week. Doing more than 150 minutes a week would be pretty damn hard, even if they weren’t all work sets. That would probably mean no rest days plus lots more assistance work.

Challenge accepted? :thinking:

I wonder if there isn’t some kind of correlational thing going on. I don’t mean steroids or PEDs generally, because the number of such users is small. Looking at sports (though this is very dirty data, with lots of confounders), longevity wise generally cardio related did well, raquet sports, track and field, running - handball and volleyball for some reason did terrible. But what argues against this, is that weightlifting and especially gymnastics did quite well:

2 Likes

Yes, it’s a good point. However, the same should then apply to endurance athletes, who burn though a ton of calories also and then replace them. However, as far as I’m aware, the threshold for endurance training to start negatively impacting longevity is much higher (I’d have to check, but I think it might be 10 hours a week or more – also, when it does start decreasing longevity, I think it’s often due to cardiac scarring, though I’m no expert in endurance training). I’d theorize this is because endurance training upregulates AMPK and not mTOR.

5 Likes

Yes, lots of unanswered questions here. Is it time spent lifting that really matters? Or number of sessions/week? Or number of sets/week? All of the above? We don’t know.

Yes, I had wondered this also. I’m fairly confident that this kind of data must’ve been collected through surveys asking “How much time do you spend resistance training per week?” or similar. So, probably most people count total time in the gym, rather than total time actually under the bar. But maybe a few people might’ve answered with an estimate of their total time actually spent doing work sets, though I’d guess that would be uncommon. So my guess is a typical 3x/week, hour in the gym each time (with perhaps 20 sets each session) would be counted as 3 hours/week in these studies.

1 Like

Interesting study, thanks for sharing! The increased mortality for volleyball and handball players is pretty odd; no idea what to make of that. (Sumo wrestlers, as we would expect, did not do well.) I couldn’t find any reference to weight lifters in this study, though, only a brief mention that “endurance and mixed sports showed increased survival rates, whereas anaerobic sports showed inconsistent results”. I thought I read about a study from a couple of years ago that showed elite Olympic weightlifters tended to die earlier than the general population, though to be sure that could be confounded by steroid use.
Gymnasts living longer is interesting; I don’t know a lot about it, but I am reasonably sure that most gymnasts have a lot of upper body muscle mass. So that would seem to be a point in favor of getting jacked. :wink:

1 Like

There are so many confounding variables here. But in general, the people I know who are gym rats are not healthy in other areas. Many have abused substances to give them an edge. Again, that’s just from the ones I know, and I have no data supporting this. I think a combination of aerobic and anaerobic is the sweet spot, especially for the brain. Nothing too extreme.

According to the table in figure 2 in that study, the coefficient for weightlifting is 1.3, just below basketball at 1.4, and basketball is pretty aerobic all things considered. The confidence margins are fully within the side showing benefits for longevity, which would indicate, at least for this study, that weightlifting even at elite levels is a positive for health. I find it hard to believe then that if you lift less than a weightlifting athlete, you shorten your life. There are confounders somewhere in these studies.

The other thing to consider is the extremely wide range of exercises in weightlifting. If you do aerobic exercises, even the name gives away the game, “cardio”, no matter what you do, you mostly are affecting your heart and lungs, hence cardiopulmonary fitness. In addition, you can affect some isolated muscle groups, usually in endurance mode - running/cycling: leg muscles, rowing: legs, arms; nordic skiiing: legs, arms.

Meanwhile, in weightlifting, it’s almost all muscle groups, and frequently you do splits. So explain to me, how if you do 30 minutes of legs one day, and 30 minutes of upper body another day, and do each split twice a week, so you end up 4 sessions of 2 hours, you are suddenly shortening your life. I could kind of understand if you are doing 2 hours of whole body muscles, you could say the muscle that is exercised for 2 hours, say, legs, is just too much for those leg muscles, and 1 hour is tops. But what about splits, you get 1 hour legs and 1 hour upper body - so you are within the 1 hour mandate, but put together, and now you’re over the limit? This is hard to wrap one’s head around.

Then there is the issue that’s close to my approach. I do my version of circuit training, if by circuit training we understand a combination of muscle and cardio components. Specifically, I do two such sessions a week, so on Mondays and Thursdays, I’ll do 32 minutes of continuous ATG squats with a light weightvest of 45lbs. The squats are structured, so 2 minute warmup regular squats, then 5 minutes of slow descent (eccentric) and rapid ascent (concentric), then 5 minutes slow descent and explosive ascent (jump - plyometric element), and so on for a total of 32 minutes with zero breaks. That way I try to cover slow twitch and fast and very fast twitch muscles. There is definitely a cardio element. I can tell you, jumping squats with 45lbs for 5 minutes continuously is super, super cardio intense, I’m breathing very hard and sweating profusely, my heart is pounding. So since I’m doing both cardio and weights in the same exercise, where do I fall in the longevity limits of 1 hour per week with this modality of exercise? You might say that 45lbs and nonstop squats is not weightlifting. I beg to differ - it depends on how you do it, if you are descending slowly on the eccentric that is a hypertrophy stimulant, and if you are ascending explosively, jumping, the actual weight is much higher than the 45lbs because of momentum - the higher and stronger your jump, the more weight pressure because you are overcoming inertia. I know my leg muscles have grown tremendously with this protocol in the past two years. It’s definitely weightlifting.

My point here is that I don’t even know how to classify a lot of the exercise people do - like my version of circuit training. So how can you divide the effect like that, when cardio is combined with weightlifting and even elements of HIIT. And the huge variety of weightlifting protocols.

I also do a bunch of isometric leg exercises - 15 minutes 4 times a week. So f.ex. one exericise is to stand on a half bent leg on the ball of my foot - one leg - and do so for 7-8 minutes (while I brush my teeth) and then switch to the other leg for another 7-8 minutes. I can tell you it’s not easy. You many think this is worthless, but you’d be shocked - in 2 years, I absolutely, positively have added muscle mass to my calfs and all around my ankle and feet, because I can see it, my wife can see it and my slim cut pants have to be thrown out. I have muscle bulges just above the rim of my shoe, which were not there before. And the common wisdom is that isometric exercises don’t result in hypertrophy - BS. I have proof otherwise. So tell me, is isometric exercise that is hypertrophic for muscles classified as “weightlifting” and therefore I should add that one hour a week I do those as my limit not to shorten my life? Because it is not cardio. Is isometric exercise shortening my life?

I don’t know. This seems very, very laden with confounders and imprecision.

3 Likes

Maybe I missed it, but did they account for steroid use?

I should already be dead then

8 Likes

The studies reviewed in the cited source Muscle-strengthening activities are associated with lower risk and mortality in major non-communicable diseases: a systematic review and meta-analysis of cohort studies do not seem to control for steroid use. The supplemental material lists covariates like age, sex, alcohol consumption, BMI, etc. but steroid use is not not mentioned in any study.

Steroid use among active weightlifters may be more prevalent than you’d think, estimates for gym goers in Western countries vary between 5% and 30% and use is likely increasing in recent years with the influence of social media. I won’t give you a citation here because I’m not happy with any of the source research I found. Let me know if you have better luck!

In my opinion, steroid use could explain the trend to greater mortality with more time in the gym. Or it could be mTorc1 activation. But mTorc1 activation in muscle ONLY (the tissue resistance training impacts) seems unlikely to cause heart disease or cancer.

Based on these studies and those that show a negative impact of high protein on longevity, I’d say more research should be done to tease out if this is real effect or simply a statistical artifact, and if mTor is involved.

But in terms of my training routine, I’m sticking with four hours a week.

6 Likes

You know, looking at this a bit more, one thing jumped out at me: “…pole vaulting showed the highest increase at 8.4 years, followed by gymnastics at 8.2 years, and sports associated with affluence, including fencing and targeting sports (e.g., archery), at 6 years.”

I wonder now how much of this could be a statistical artifact just reflecting differences in socioeconomic class. It seems clear that things like pole vaulting, archery, and fencing are activities almost exclusively pursued by people with wealth and some amount of leisure time. Whereas things like basketball and weight lifting are much more popular with the masses, especially blue collar types (in my experience). I think that could also explain why racquet sports seemed highly correlated with longevity, while handball did very poorly. They are practically the same activity! (just one with a racquet in hand, the other no equipment)

Someone else brought up the issue of steroid use as a confounder. I had wondered about that too. I didn’t really think steroid use would be THAT common, but maybe it’s more prevalent than I realized. While I think the socioeconomic class confounder might be a bigger factor, steroid use could be playing something of a role here too.

5 Likes

I guess I’m not up to date on these. Does anyone happen to have any links to studies where high protein intake seemed to reduce longevity? If this is true, it definitely could be an explanatory factor. People who lift weights are much more conscientious about getting in high amounts of protein to facilitate muscle growth.

And if this is so, then it raises questions about strategies to both enhance muscle growth while also not shortening your life span eating too much protein…

Most of my comments here are directed ad men 65 and older. I have been reading and experiment along these lines and my experience has led me to lifting less often and with no more than 80% of 1RM. Ther result has been increased muscle mass and strength.

The literature on longevity and weight lifting being an inverted U-shaped curve is not tremendously strong once you remove the outliers like extreme bodybuilders and the extremely frail. For the rest of us, the contributions to reduced longevity due to excessive weight lifting are multi-causal and include:

Increased Injury Risk. Very high intensities or volumes increases the risk of musculoskeletal injuries which can reduce mobility and quality of life, negating the benefits of exercise and even initiating a downward spiral in the extre,s
.
Elevated Systemic Inflammation. While moderate exercise reduces inflammation, intense or prolonged resistance exercise can cause acute elevations in inflammatory markers such as IL-6, TNF-α, and C-reactive protein (CRP). Over time, chronic inflammation induced by high training loads can contribute to negative cardiovascular and systemic health outcomes.

Hormonal Dysregulation. Excessive resistance training, especially without adequate recovery, can lead to dysregulation of hormones such as cortisol and testosterone, contributing to fatigue, metabolic dysregulation, and muscle breakdown (overtraining syndrome).

Cardiovascular Stress. While strength training is generally beneficial for cardiovascular health, excessive focus on high-intensity training could elevate blood pressure, placing additional strain on the heart, particularly in older adults with pre-existing cardiovascular conditions. Older men should be especially aware of the possible fatal risk of rapturing an undiagnosed aneurysm. Improper breathing techniques or lifting beyond 80% of 1RM increases that risk

Lifting for more reps and sets at 60-80% of 1RM can actually build better muscle while reducing risks.
An evidence based rule-of-thumb is Reps=6-14, Sets=3-4 and the muscle group should be exhausted on the last rep of the last set. Frequency should be 2-3 times per week. More might be less for longevity and is definitely less for older men.

1RM can be estimated without risking injury using the following formula:

1RM = W × (1+0.0333×R) where 𝑊 = weight lifted and R = number of repetitions performed to failure.

Shoot for 8-10 reps to find your 1RM in a risk-reduced way. There are a few other formulas but they all come out about the same.

One other technique I picked up someplace along the way is to complete the contraction phase of a movement quickly and the relaxation phase very slowly. It seems to increase strength for me.

Bottom line: where I was going to the gym five days a week, I now shoot for three and occasionally end up doing only two. The results are definitely better.

6 Likes

Great info here, thanks! This suggests that, especially as one gets older, it’s important to manage fatigue and cycle training, with perhaps extra rest after times of more intense/frequent training. I wonder if something like curcumin might help avoid the pitfalls of excess systemic inflammation. So it sounds like nowadays, you’re actually building up more strength and muscle by lifting less frequently? Good to know. I’m only 44, but have recently backed off to lifting 3x/week due to concerns from the studies I had linked to. Sometimes I’d like to lift a bit more often, but have conflicted feelings over whether or not it’d be a good idea.

1 Like