Excellent point. I’ve noticed an extended period of muscle soreness from intense workouts done in the first few days after weekly rapa dose compared to identical workouts done later in the cycle or during a wash down. I was wondering if I was wasting effort to be working out when rapa level is high. I hadnt considered that I also might be blunting the effect of mTOR1 inhibition. Yes, I hope that Blagoskonny will address this issue.
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It really could go either way. I do one 72 hour fast per month. The rest of the month, my exercise is all Brazilian jiu jitsu plus supplemental cardio, but during my fast I add in weights (squats, deadlifts) to preserve muscle mass through the fast. Peter Attia is pretty adamant about doing this through his fasts–there may be a parallel for rapamycin?
I’m still waiting for my order to arrive from India. Once it does and I start, I’ll report back. I measure everything every morning (RHR, HRV, blood glucose, lactate, etc.). HRV especially may show how how the rapamycin is impacting recovery.
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I just think it’s important to keep in mind that we’re talking about 2 separate (albeit related) things here. 1) the effect of rapamycin on muscle growth/recovery from intense exercise, and 2) the effect of exercise on the long-term muscular benefits of rapamycin
Topic #1 would be the acute effect of rapamycin on dampening mTOR and acutely inhibiting protein synthesis after high intensity exercise. We know from at least one recent study that there are some redundant pathways for muscle protein synthesis, such that we can still get some hypertrophy even in the presence of rapa, albeit less.
Topic #2 (and the most important by far, IMO) would be the possible blunting of mTOR suppression by high-intensity exercise during the 2+ day window of maximal mTOR suppression by rapa, repeated week after week x months/years. The blunted mTOR suppression could partially negate increased autophagy, stem cell rejuvenation, etc etc.
Even if mTOR suppression by rapa can’t be directly blunted by exercise (or insulin spikes, etc), might not some of those same redundant non-mTOR-dependent protein synthesis pathways blunt the otherwise-beneficial effect of the rapamycin? It still seems, at least intuitively, that we’re wishfully thinking we can have our cake and eat it too by training intensely during maximal mTOR suppression periods, but I hope I’m wrong!
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Ok, this researcher and I seem to be on the same page. He’s designed a study where he wants to give rapa 5mg once weekly to older adults and have them exercise, seemingly on the days when mTOR is not maximally inhibited (although he doesn’t specifically give the weekly timeline), to see if this regimen increase muscle size/performance over and above placebo+exercise. He explains the rational very well in the included video.
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I plan to start rapa this weekend and I’m still thinking about the optimal scheduling, particularly in light of your Topic #2.
Sundays are usually my rest day. I was thinking of taking the rapamycin directly after my noon BJJ class on Saturday, but it looks like the exercise activation of mTOR lasts at least 24 h post-exercise. So maybe I take the rapamycin Sunday morning early, which gives me until Monday evening with no exercise. Maybe I’ll throw in fasting on Sundays to help.
Between 24+ hours for exercise-induced mTOR activation and a 2-day window of maximal inhibition from the rapamycin, there’s no way to make a weekly dose work perfectly. I’m going to start weekly, but am increasingly interested in how those of you who are doing larger doses every 2 weeks feel that approach is working.
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Relevant to this discussion on rapamycin and muscle growth are these comments here:
and
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I have had positive muscle-building results.
My results:
Under possible placebo effects:
I feel much more energized and complete more tasks, less procrastination.
Results I didn’t expect, therefor much less likely they are placebo effects:
One: The biggest surprise which I didn’t notice at first, probably because it was a gradual cure.
I am 80+ years old and had developed age-related "essential tremors’’ in my hands. I wouldn’t be able to eat peas on a fork and get them to my mouth. In fact I was starting to get embarrassed when eating with company. Then a couple of weeks ago I was eating and said in my mind; WTF!, my hands are not shaking anymore, in fact they are as steady as they have ever been!
Second: I go to the gym 3-6 times a week. I had "plateaued’’ on the max weights and sets I could do. I must mention that I have been taking care of myself and taking a lot of supplements, including NMN, metformin, etc. I have never suffered from sarcopenia.
Now I have passed the plateau and have increased my max weights and increased my sets from 3 to 5. People probably are skeptical, but I have never been stronger.
To those that are younger: You probably won’t notice much, because you are not broken and probably don’t need fixing.
My blood tests are very good with a slight decrease in white blood cell count, down from 9.1 to 7.9. still within normal range. After a 6 week wash-out period, I will test again before I start a second 100 mg total dose at 10 mg every 14 days. This may tell me about the effect on my white blood cell count. I didn’t notice any effect on other blood tests, as they are already good.
And again, under possible placebo effect, I have never felt better.
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I’ve now been on rapamycin for 6 weeks, not counting one week where I skipped my dose because I had omicron. I’ve maintained a consistent schedule. My last training session of the week is 12 to 2 on Saturday. I take my rapamycin Sunday morning first thing. My next training session is Monday at 6PM. My training is Brazilian Jiu Jitsu, and while I do supplemental strength and cardio, I don’t do it during that rapamycin window.
My take-away so far is purely subjective–no biomarkers–but I’ve been doing BJJ for 13 years, 6 days a week. I’m a 50-year old black belt with asthma, rolling with 25 year old lower belts, so I have what I think is a good sense of my energy expenditure. Sundays have been my rest day for the last five years.
Pre-rapamycin: Those Monday evening classes tended to be ones where I had the most energy. Then I’d gradually get worn out over the course of the week, etc. The end of the week was usually at a far lower energy level.
With rapamycin: Mondays are noticeably low energy. This may be compounded by fasting on Sundays. I do eat a late lunch Mondays to refuel, but I nevertheless feel fatigue much sooner during the Monday training. On the flip side, however, I seem to have a much better recovery capacity at the end of the week.
I’m still somewhat undecided on the optimal timing of the rapamycin given my schedule: whether to eat it Sunday morning, or Saturday night. Mikhail Blagosklonny offered me a partial answer in a tweet, which I took as “don’t overthink it.”
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Just curious on everyones training protocol in terms for longevity?
I am 24 , 170lbs and do a combination of Kettlebells, Gymnastics and gymnastic ring work. zone 2 cardio and yoga . I usually do a 3x a week of anaerobic training, and 3x week for cardio training.
I am more focused on making my body “bulletproof” in the next 3 years instead of being completely jacked or body builder.
I dont really do much weight training and focus mostly on body weight
I was wondering if I should change my philosophy or if you had any recommendations to add to my training regime.
I also eat a low carb diet/high protein with IF and TRE.
thanks
Looks like you’re hitting all the pillars of fitness there. The composition should naturally reflect your goals.
My one reservation would be the frequency of the high CNS components. Three anaerobic sessions per week in addition to callisthenics/KBs seems like a lot…
I think if you do one of Pavel’s protocols e.g ‘Quick and the dead’ (KB swings plus explosive press-ups or dips) 2 or 3 times a week with Zone 2 on the off days then that’s a great foundation for ‘health’.
If you want to lay a greater foundation of muscle mass for your later years then doing compound lifts like deadlifts or squats would be preferable, e.g. via the ‘Texas method’ in Starting Strength.
In my experience competitive sport isn’t ‘healthy’. Recently I started training seriously again (cycling) after a couple of years of just ‘exercising’. I started with a CP20 of ~300w and now I’m up to 338w which is only 15 off my best from ‘16. BUT all my health markers (resting HR, HRV, CRP, free testosterone etc) have got worse.
My recent reading suggests TRF is sub optimal for body composition but I know this is a highly contentious subject. Regarding diet I would refer you to @mkaeberlein recent paper: Science | AAAS Basically, it doesn’t make much difference!
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Yeah I figured, it seems in regards to diet that there is so much different literature that I think if you just take some general mindfulness into what your eating, then as long as you are doing everything else(exercise, good sleep, low stress,etc) then you are fine.
I should’ve said, that in regards to the anaerobic training that I consider my body weight/KB stuff as my anaerobic training, I dont do all of that on top of serious weight lifting.
I also follow Pavels 3- 5 minute rest between sets to ensure that I am not overdoing it.
I will look at the other methods you suggested!
Thanks again
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I agree with Maveric that competitive sport isn’t “healthy” (the number of injuries I’ve had from rugby and BJJ is absurd) but there’s nothing like becoming obsessed with a sport to keep you exercising through decades.
At 24, your optimal workout will look very different than mine at 50. I do think it’s important at a younger age to build up a reserve of real strength–compound heavy movements like squats and deadlifts. I haven’t squatted in 5 years, but at 45 I still had a 500lb squat for 5x 5. I stopped because the risk (to my spine, heart, blood pressure, etc.) vs reward shifted as I got older. Now I only deadlift light weights in a trap bar to keep my posterior chain strong and balance out all the pulling in BJJ. But the strength and stability I built up from those compound movements have served me well, protected me in accidents, etc.
If your goal is longevity you don’t want to become a powerlifter, and you want to always balance your parasympathetic with your sympathetic systems, but there are correlations between muscle mass during early years and longevity. The risk from heavy lifting is a thickening of your cardiac muscle. To simplify, endurance sports will enlarge your left ventricle while power sports will thicken the muscle. That’s not good for longevity, so it really does have to be a balance.
Best resource I know for balancing those two systems is Joel Jamieson. The material is largely targeted to mixed martial arts, but MMA is a sport that really requires both strength and endurance. Joel takes a highly scientific approach, with a big focus on recovery. (Which at 50 is everything, but even younger is important.)
My own programming is suboptimal for longevity, simply because I enjoy the sport too much.
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I am big into MMA as well. I got away from BJJ due to risk of injury that could occur or the wear and tear to my joints. I wrestled and did MMA most of my childhood.
I will check out the article and Joel Jamieson.
Thanks!
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Do you have any thoughts on doing Layne Norton’s PHAT(Power Hypertrophy Adaptive Training) method?
Or should I change up and focus on strength training/muscle building for a couple months
Then go back to a 3/3 schedule (3 days anaerobic and 3 days aerobic)
I am just trying to find a good schedule or cycle to ensure that I am geared towards longevity but also not plateauing or missing out on good opportunity being young
I find Peter Attia’s information valuable as I’ve refined my exercise program that is balanced between strength/weight training, cardio / zone 2 training (biking, rowing machine, running, etc.)…
See this podcast:
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If you’re above a certain fitness level, it’s hard to make progress in aerobic and anaerobic simultaneously. Some of these adaptations are in tension with each other. I suggest working in 8 or 12 week blocks where you focus on one system but do just enough of the other to maintain it. For example, focus on cardiac output by increasing that to 4 or 5 days per week, with only 1 or 2 for strength maintenance, and even that at a lower volume. Then switch to strength 3 or 4 days per week and cardio only 2 days for maintenance.
Your programming within the week also matters. Standard would be to have two stress-recovery cycles per week, with light, medium and heavy days (in terms of stress/volume/intensity, not weight), plus one active recovery day. But programming is an extremely deep topic and depends on a lot of variables.
As for Layne, I enjoyed his episode on Peter Attia, and I follow him on Twitter, but I’m not familiar with his protocols. His love of carbs puts him in a different philosophical camp from me. I enjoy listening to the other side, but it doesn’t make me gravitate to his methods.
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I’ve actually listened to this podcast and found it very good just wanted other perspectives especially the people on this forum
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Do you have any good references ?
Also this is Lanyes PHAT
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Also I wanted to ask in regards to blood work. Do you go through a lab specifically? Or do you ask your doctor to get the lab work done?
I ask because the longevity doctor I was planning on working with does blood work via LabCorp and its around 450$
It would include
- CBC with Diff
- Metabolic Panel Comprehensive
- Ferritin
- Lipid Panel
- Testosterone free and total
- DHT (dihydrotestosterone)
- Luteinizing hormone
- Estradiol
- DHEA
- IGF-1
- PSA
- Thyroid Panel TSH, T4
- T3
- Cardio CRP
- Homocysteine
- Cortisol AM
- Fasting Insulin
- Vitamin D
- HgAIc
- Urinalysis
But I was wondering if this is something I could get done via my primary care doctor and save some money or anyone has done this through other methods?
I think you’ll get a range of responses here… if a person is seeing a longevity-focused doctor then they may get the tests as part of the service from that doctor. But even then - they may not see you that regularly and they may not do that much blood testing other than the annual physical / testing.
Many of us here like to see more regular and frequent blood test results to track progress (or not). There are some great inexpensive tests for CBC , C-reactive protein (high resolution) that are quite cheap, from LifeExtension.com (working with Labcorp) - and this is very helpful for identifying / calculating Levine Phenotypic Age, or Aging.ai numbers. I try to do this at least every 3 months or so to track progress and see results to any changes in my longevity protocol.
See more discussion here on Blood Tests.
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