I’ve been head-scratching today on the paradox of MTOR activation. We know that MTOR is over-expressed as we age and modulating it with Rapamycin has a number of health benefits.
We also know that sarcopenia (muscle loss as we age) is bad. We are told to eat a lot of protein to combat this. Why? Is it because we need more protein to counteract our bodies’ inability to absorb protein or its inability to put it to use? Or, do we need more protein simply because protein presumably has some amount of Leucine in it, and we need Leucine to trigger muscle growth?
To complicate matters, Lamming Lab recently demonstrated that Isoleucine (another branched chain amino acid that would be found in similar concentrations to Leucine), when restricted from the diet of lab mice, resulted in significant longevity benefits.
I’m wondering. . . does it make sense to specifically supplement Leucine, timed with exercise, to crank up MTOR and use Rapamycin on rest days to dial back MTOR and kick in some autophagy? In other words, instead of relying on our natural biochemistry to dial MTOR up and down, what if we toggle it with Leucine and Rapamycin?
And, while we are at it, maybe we can eat less overall protein, and thus eat less Isoleucine?
Does anyone know of specific lab work in this general direction or is anyone self-experimenting?
Good questions. I used your post verbatim as a query in ChatGPT 5.
FWIW, here are the results:
Quick answers to your specific questions:
“Do we need more protein because of absorption or because muscle can’t use it?” Mostly muscle-level anabolic resistance, not a dramatic failure to absorb, though absorption can be somewhat slower/inconsistent with age. The fix that consistently helps is larger per-meal high-quality protein + resistance exercise.
Frontiers
SpringerLink
“Should I supplement leucine timed to exercise?” Reasonable if your per-meal protein is otherwise low in leucine, but best results come from complete protein (or EAA mixes) delivering ~2.5–3 g leucine rather than leucine alone.
PMC
+1
“Could I toggle with leucine and rapamycin?” You can separate rapa from your hardest training by ≥24–48 h and front-load protein/leucine on lifting days. That’s coherent with human physiology data, but it’s still untested as a longevity protocol.
PMC
Bottom line
Keep training days anabolic (hit the leucine threshold with complete protein).
Keep rapamycin days away from lifting; don’t stack rapa right before training.
Be cautious with overall protein restriction at your age; consider “low-ish on rest days,” not low.
Treat isoleucine restriction as experimental until human data arrive.
Since listening to Brian Kennedy on Peter Attia’s podcast, I have been thinking about mtor resistance. We might take Rapamycin or fast to keep mtor levels low, but what we want is the healthy mtor regulation of a younger person. So an older person in whom mtor remains switched on all the time might be analogous to insulin signaling in a type 2 diabetic. Leucine causes mtor to rise and Rapamycin blocks this effect. Leucine cycling makes sense to me.
Great question and one that I’ve been concerned about for several months. The sarcopenia and osteopenia (or osteoporosis) of aging have caught up with me. So, I’m in an anabolic stage at this time and I’m considering a variety of things from peptides to SARMS (low dose) seeking slow, safe improvement in muscle volume and bone density. Even regrowing the Thymus during this time is something I’m considering. But, it’s all still in limbo.
I want to put Rapamycin back into my plans, but I don’t want to take the chance of destroying my anabolic phase. So, I’ll delay it for 9 more months at which time I’ll see if I’ve made any progress with muscle and bone before incorporating Rapamycin again.
I would prefer to go back to the weekly Rapamycin schedule, but I don’t see that as giving the anabolic phase enough of a runway to work well. I’m considering once every two weeks at a higher dose or maybe three weeks. But, I likely won’t do it.
Like Desert Shores, I also asked ChatGPT about this earlier and I got answers similar to his. I even put in all potential treatments I’m considering, plus Rapamycin and asked ChatGPT to create what it considered a reasonable dosing schedule to make the catabolic and anabolic phases successful. I got a very precise weekly dosing schedule with the warning that it’s entirely experimental! Well, of course it is! When I took Rapamycin out of the equation ChatGPT was somewhat more positive about my approach.
I wondered whether low dose SARMS could be effective. It seems that the bodybuilders find out first what works for them, but they don’t tend to live very long lives. I would think low dose SARMS could work like low dose TRT.
What is the latest on Thymus regrowth? I remember something about Greg Fayhe’s company, but it felt to me like their results were clouded by all of the DHEA and HGH they were pumping the patient with. There is also Thymmune Therapeutics. They seem to be doing real science, but I have not heard how they do it or when they will be ready for human guinea pigs.
Also, there are a bunch of companies trying to make companion drugs to GLP-1 agonists to preserve muscle mass. I wonder if they are onto anything.
Is there a good reason not to exercise when dosing rapamycin? Is it just pointless or is there a concern that MTOR stimulation from exercise could offset Rapamycin benefits?
In my opinion the “big guns” for muscle growth and improving bone density are hormones and SARMS (SERMS too). And, of course, that includes TRT. I’ve been the full round in trying all sorts of supplements including DHEA, boron, ashwaghanda, DIM, Tongkat Ali, etc. and found none to be very effective for me in raising FT, although DHEA will raise DHEA in the blood and increase TT noticeably. I’m now back to trying Enclomiphene a third time to get FT up for it’s beneficial effects.
At this point Ostarine, Ibutamoren, and Tesamorelin (HGH secretagogue) look interesting and there may be others I have not found yet. Which ones will work at a low enough dose to not upset the HPG axis is what I’m seeking. Including Enclomiphene with some of these could also possibly raise FT some, but of course it’s just experimental.
Ipamorelin and CJC-1295 no DAC (HGH secretagogue) are also interesting.
What will work to provide muscle and bone growth for a while without upsetting the body’s natural feedback mechanisms is what I currently seek. Of course, the simple approach would simply be find a doctor to prescribe TRT + hCG and HGH treatment, but I’m not at that point yet.
Fahy’s TRIIM protocols for Thymus regrowth? Everything I’ve read says that it’s been successful. There are people here doing it in their own way without going through actual TRIIM Trials. From my point of view the most important medicine being used in the trials is HGH. Maybe I can get the same effect with CJC-1295 (no DAC) of Tesamorelin. Search for “Agetron.” I believe he’s currently doing his version of thymus regeneration. Or, maybe just search for “thymus regeneration.”
I will have to check in with Agetron. He encouraged me to test drive TRT. I started that about 2.5 months ago. My doctor referred me to a local urologist who seems to dispense it like candy! He is of the opinion that all men should try it and see how they feel. My FT was low enough that it seemed better justified that “just try it”. I’ve been on it for almost three months, but have not done blood work yet. I will do that first week of Sept and am curious to see what comes back. I’m not feeling different at all, but it seems that the veins in my forearms have popped at bit.
Yes, I think it is counterproductive to exercise on rapamycin days. It sort of defeats the purpose. I also don’t exercise on the day after taking rapamycin because I am usually tired the day after taking rapamycin. Currently I am exercising five days a week and take two days off for the rapamycin.
Jay, I have observed increased anabolic response to resistance training starting about 5 days after the Rapamycin dose. (N=1 might be worthless, etc.). I was training fairly heavy and had my deadlift up to 275 before I fell and broke my back. Weekly Rapamycin does seem to stall gains, but then muscle growth spurts seem to occur when I stop. I have a quantity of lgd4033 in my basement, but I have never taken any of it. My testosterone level remains good at age 62, and a sarm would tank testosterone. If I was already on trt, I’d consider lgd4033 or osterine. The main thing is you need to squat. Good luck.
Low dose ostarine at 1mg a day for 12 weeks didn’t impact free testosterone, but did impact total testosterone, reducing it by roughly a third . 3mg daily lowered it even further. So you can see that even at those low doses, the hpg axis is partially suppressed. And no one in the body building community is taking these small doses.
A broken back sounds pretty bad. How did it happen and how long did recovery take?
Sarms and testosterone: Yes, a standard Sarms dose will tank testosterone. I’ll be checking my low dose approach specifically looking for that.
Deadlifts and squats. I don’t do deadlifts, but I am considering it for bone density improvement. I do, however, do weighted squats (a lot) twice weekly and I don’t enjoy them at all.
I did not find a reference to testosterone in the study, but it is a definite concern and I’ll take your word for it. However, FT not TT is my major concern.
I fell off my deck and landed across the bottom step breaking a two by six in half. I thought I had fully recovered in a month and a half, but I occasionally have lingering discomfort. In my experience it is possible to add muscle mass while taking rapamycin.
N=1 here. 72yo. 165#, low BMI no number known. Been on rapa ~3-4 yr can’t guess more accurately. 10mg ish with adjuvants targeting 20-25 (??) units blood level. I’m a poor absorber it appears.
Peptides: Ipamorlin/CJC + Tesamorlan upon wakeing 1mg ea M-F
2-3x a week; only 10 min at: 20# hand weights on a vibration plate in front of a toe to head LED panel set. Approx 1kw input. Then pushups now up to 60. Have peaked at 70.
Approx 100g protein / day. Low carb, gobble good fats; ghee, butter, steric acid (lamb), fish oil, plasmolgens (prodrom.com).
I’m growing muscle. Nice arm buldges. Nice leg thighs. . Toss 60# bags of cement. Can lift 80# bags but don’t like to. That crosses my backs line.
Bottom line; I see no hindrance taking rapa re the possibility of growing muscle at 72yo, if enough tricks are put in place in parallel. the kaatsu.com (C4 the cheaper unit, order large bands sizes are Japanese) is under appreciated and allows someone as lazy as me to grow muscle. I don’t consider the vibration plate for 10 min that essential or even 20# weights. IMHO its the HGH boosting peptides, >= 100g protein, and the kaatsu.com.
@Davin8r, there’s a dozen sites selling peptides labeled as experimental use only where each 10mg of ea is around $70 +/-. solution peptides, can labs, limitless, the place I’ve decided to give my buys to is uniting wellness.
BUT I agree when it seems cheap you go over board and add a mirad of protocols, injectable bioregulators, oral bioregulators, nearly the full range of peptides. Kitchen sink.
Efficacy? Yes some muscle, DSIP + Epitalon + Ipamorlin before bed does help sleep (on top of Mg, Glycine, melatonin)… Probably some anti-inflammation from BPC157+TB500. Not certain of course because of the kitchen sink when some sneeze or flue symptom happens; Thymosin-A1 (also take oral ProBoost over the counter product), Thymulin… Then the tiny amount of GLP1; tirzepitide+Retatrutide 50:50 maybe 600mcg/week; enough to keep the brain et al receptor sites happy and functioning. The GLP1 is cheap since so little used / week and at $80 is / 10mg all is +/-.
My peptide kitchen sink might be $300-400/mo
By far the most expensive nutricals and with very little seen benefits are; StemRegen, ProDrom plasmologens, C60 by wizard sciences. Rapa is nearly free in cost comparison.
My studies are finding PlasmaPhoresis with adjunivants added like at the Nashville TN facility: Maxwell Clinic. Amazing testimonials. True re-treat frequency is high. Haven’t called to price a “package”…
The post stem cell era: exosomes now coming transplanted mitochondria.
@curt504 I was only referring to CJC and tesamorelin. They bind to the exact same receptor (GHRH receptor), so it doesn’t make sense to take both at the same time.
Out of all the ghrh peptides, tesamorelin has by far the most solid data behind it, from phase 3 clinical trials . That’s fairly rare for a non GLP1 peptide. I would not bother with the cjc, frankly. @Davin8r is right.