I believe, also based on affirmations from David Sabatini, that it is impossible to overactivate mTOR, especially in muscles, by simple exercise and nutrition. mTOR after a certain exercise threshold becomes insensitive, that is, the inhibiting inflammation and metabolic pathways like AMPK prevail and the sum effect is a downregulation of this protein kinase.
The key is to adopt an adequate strategy of cycles of interventions and recovery, each of these phases calibrated according to the neurological signals we receive from the muscles and connective tissue.
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The study he cites (Momma) notes that the studies included in the meta-analysis used “self-reporting methods” or “interview methods” to measure muscle-strengthening activities. I am as skeptical of this as I am of dietary studies based on self-reported eating habits. Unless the subjects kept an exercise log and could tell you exactly what they did over the past X number of years, the number of “minutes a week” they spent exercising is just a wild-ass guess and I would not attach a lot of importance to the conclusion that the optimum number of minutes a week is 40-60 and that over 130 minutes is “too much”.
That aside, “Physionic” doesn’t look like a guy who has lifted heavy for 15 years. 
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Wow! This is incredible. I do not believe I could have done this when I was in college, and I was a decent athlete then. Your routine is not for the faint hearted. Very impressive.
I would bet an enormous amount of money that this routine is life extending.
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I tend to agree, there is too much uncertainty over a number of variables that are very significant to the aspect of a dose-response model. The type and number of exercises, the intensity, the time under the bar and time in pause, the dietary regimen, the use of androgens and so on…
I would be very interested about the comments of some researchers in the field like Brad Schoenfeld.
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So while reading through that thread on the CR Society that someone linked (thanks!), I found this post (from “IgorF”, towards the bottom):
"What was unambiguous was that after the researchers injured the same muscles, senescent cells emerged in small numbers in the young mice, and they erupted explosively after the same injury in old mice. And while these senescent cells either retreated or were cleared by the immune system two or three weeks after injury in the young mice, they stubbornly clung on in the old mice.
This looks exactly like cancer risks (for 90% of variants) and age - when immune system starts to decline it deals with cancer cells killing worse and risks are growing faster than in young/midage. So excercising hardly in the older age could complement to the ACM stats in the cohort studies (givnen that strenous excercises should produce more injured tissues then endurance and recreational excercising). Speculations off course."
This looks pretty interesting. Perhaps older lifters just can’t recover nearly as well from muscle breakdown as younger ones can, and these leads to increasing cellular senescence? If yes, maybe periodic breaks from training + fisetin might be a good idea for older lifters?
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Sorry, I don’t have the references at my fingertips, but if you check out this thread you can get citations and more opinion: Eating Too Much Protein is Bad for Your Arteries, and This Amino Acid is to Blame (UPitt) - #107 by Davin8r
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There is some interesting research by Luc van Loon on anabolic resistance and overcoming it with resistance training in older people. Although many assume that anabolic resistance increases with age and that muscle loss is the enviable result of aging, he has shown that our sedentary lifestyle is actually the culprit. In fact muscle tissue in the elderly can be made identical to that of healthy young people through activity and resistance training. You’ll find and interesting discussion of it on Attia’s podcast: Optimizing muscle protein synthesis: protein quality and quantity, & the key role of training.
I can say from experience that I’ve added more muscle through resistance training at 65 then I was able to in my 40s, by increasing my volume of training by about 30%. The only negative is I need to be more cautious with my knee and shoulder joints, so for things like the the squat or should raise, I’ll use lighter weights for more repetitions.
I have no intention or interest in getting “big” but I do want to capture the metabolic and mobility benefits of a reasonable amount of strong, lean muscle. And looking fit and young is an immediate reward that helps motivate consistency.
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Another factor that may result in findings of strength training being negative in this context is a lack of aerobic exercise and total focus on lifting.
Aerobics help tremendously with blood circulation and cardiac strength. If one only lifts, it can actually inhibit blood circulation. Many men who lift believe that “gains” can be dissipated by aerobic exercise, so they avoid it. But it is obviously not the optimum health decision.
I think that older age CAN point toward less training. But my approach has been the opposite. I am doing more than ever by going with more reps / sets and less weight. My weak point are my joints and tendons. But it is manageable with ongoing care and support as needed.
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In training always keep in mind that muscle hypertrophy occurs faster than tendon adaptation. So when doing progressive overload, don’t increase weights too fast, let the tendons catch up. I believe I also heard that on one of Peter Attia’s podcasts. In general, once you are an adult, your tendon size is pretty much set, however you can still strengthen them. As a rule, especially as I get older I favor much slower intensity escalation, prefer lower weights more reps, longer recovery breaks.
Interesting fact, certain anti-inflammatories like ibuprofen tend to blunt muscle gain and adaptation if used too closely to the training session - BUT, past the age of about 70 or so, that is no longer true, and in fact, anti-inflammatories like ibuprofen actually assist in muscle recovery, and protect and enhance muscle adaptations. The reason, it is speculated, is that the inflammation that results from exercise is no longer tamped down as efficiently by the body, so by your next workout session you still have some residual inflammation, and in time, you stack that inflammation higher and never fully recover, which comprmises the beneficial effects of exercise on muscle growth and adaptation. So ibuprofen in the elderly can assist in tamping down that residual inflammation if taken a few hours (not immediately!) after exercise. I myself - now that I’m getting older - have taken note of this phenomenon, and no longer hesitate to take things like vitamin C or astaxanthin 6-8 hours after exercise in my evening meal. Before, I used to avoid taking them on days I had heavy workouts.
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A great point. A tendon injury can nag you for life, and set you back a long time. Never push at maximum force without YEARS of buildup. I never have weight or reps goals. I never push to accommodate anything but fatigue. If I feel a twinge I’m done. If a tendon remains tender after 48 hours I skip that muscle group in that workout. I never lift anything I can’t lift at least 8 times with perfect form in a set.
Dynamic movement (sprinting, jumping, high speed change of direction) are very dangerous. Build up very slowly.
Consistency is king. Be patient. Learn to like the experience rather than the accomplishment. After a few years you will look better than you expected (if you lose the fat layer also).
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Great advice, well written! 
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I wonder if a large part of the ordering reflects not the sport itself but the socioeconomic group of the typical participant.
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Having considered that study some, I am pretty sure that is a part of it. The study even explicitly noted that sports associated with affluence appeared to confer a 6-year bump in longevity. Archery was one such. I seriously doubt that archery confers great longevity benefits from its cardiovascular demands (though maybe a bit from strength and coordination…but I doubt it’s as good for those as a lot of other sports on the list that didn’t appear to boost longevity as much).
Benching 320 at age 74. An inspiration to us all!
He does not take any drugs or supplements - he despises “the drug culture”.
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So, to sum up some things I might’ve learned from all this:
– Socioeconomic factors may be a confounder for those who lift weights frequently (vs., say, runners or tennis players).
– Systemic inflammation may be an issue for older lifters (this would explain why ibuprofen seems to improve gains in older lifters, but worsen them in younger ones).
– Very high-intensity training could lead to elevated blood pressure and higher risk of aneurysm.
– People who lift weights frequently also typically consume larger amounts of protein, more frequently. This makes sense for the goals of increased muscle and strength, but higher protein intakes, particularly of animal protein, may lead to decreased longevity. Possibly this is due to methionine build-up.
On the last point, I’m becoming increasingly convinced that supplementing glycine is a good idea, particularly for people who do consume a lot of animal protein. This can help counter the excess methionine, and there are several studies (linked to in other threads on this site) that indicate that increased glycine intake may boost longevity. Towards that end, I just bought some supplemental glycine and will plan to start taking a few grams of that regularly. So that’s my takeaway from all this so far.
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Sometimes it’s not systemic but rather local inflammation. Muscle tissue, and connective tissue, they tend to get inflammed and provide nagging aches and pain.
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I was thinking somewhat recently about the fact that when you lift heavy weights, it tends to spike blood pressure, and then this may be harmful when done over many years (as I have done). e.g. it may weaken arteries or something. I wonder if it can be mitigated by, for example, working one arm and one leg at a time, instead of both together at once…
I posed the question to GPT-5-thinking, and here were the results:
Short answer: Yes—doing heavy lifts one arm at a time generally blunts the cardiovascular spike compared with lifting with both arms simultaneously, especially for upper-body work. Studies that directly compared the two found higher heart rate and rate-pressure product (a proxy for cardiac workload) during bilateral biceps curls versus the same exercise unilaterally; systolic BP itself rose in all cases, with between-condition differences smaller and sometimes inconsistent. Overall, unilateral tends to mean less total muscle mass at once → a smaller pressor response.
…
Bottom line: For heavy arm work, one arm at a time usually means a smaller spike, but breath control and proximity to failure are the biggest levers for safety.
Breath control is something I need to pay more attention to. I often catch myself not breathing during a rep and have to correct.
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Recently, I made a small change to my weightlifting technique that is recommended by Attia and others to prevent tendon and joint injury, especially in older adults. I’m still performing between three and five sets at a rep of 10 or below, and a weight target aiming for near-exhaustion on the last rep.
What I changed is the method for performing each rep. Taking a preacher’s curl as an example, I contract as rapidly as I feel is safe, explosively if I can. I then release very slowly, a minimum five seconds and as long as 10 seconds. When I am close to the bottom of the rep, I begin the next rep without ever unloading the muscles.
The rationale for this strategy is preventing injuries, which are said to occur mostly in the release phase of a rep. It is also a technique used by bodybuilders to increase size. For me, the size issue is immaterial and, in any event, the empirical correlation between mass and strength is fairly high. By performing an entire set without unloading the muscles and extending the release time, I experience and intense burn much more quickly and with lighter weights that place less stress on joints and tendons.
You can find extensive technical discussion on the benefits and downsides of this technique. My report here is only that, at 80, I am definitely building strength faster, with lighter weights, and no injuries even though I work the muscles to exhaustion. As an example of the strength build I have maxed out the weight stack in a couple of the 12 machines in the circuit.
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Ted Nugent Jr.
… Yup