Some one wrote on the forum – I saw, on dogs I believe, that specified the brands of rapamycin used. They used Zydus and Dr. Reddy.
This latest batch I received is 3 months worth comes from Accredo pharmacy (physician prescription) is Dr. Reddy Brand. Tan pills with red lettering RD 54 looks the same.
Yes, not going far enough. If we are doing a truly significant blockade of mTOR with rapamycin, ergo cell cycle growth arrest, we should be seeing MAJOR weight loss as a signal. This is what blunting mTOR does across mammalian species. You’d think at least some people would be reporting significant weight loss? Thus, my grand reservations.
Until I see tissue markers, gene expression, mTOR inhibition markers and in general, the recapitulation of the mechanistic pathways in mice, I am highly suspect. I continue to advocate we need a new paradigm…a NEW way of increasing “rapalog” tissue uptake with lesser side effects. I am under no illusion that current ORAL RAPAMYCIN is NOT going to be the ultimate lifespan enhancer in humans. It may deliver some level of healthspan, but I seriously question lifespan.
Getting these human markers is obviously extremely problematic, but human impediments are going to prevent the full biological reveal.
Here’s a paper on prostate cancer and ACTUAL mechanistic mTOR tissue markers from tissue.
Activation of the mammalian target of rapamycin signalling pathway in prostate cancer and its association with patient clinicopathological characteristics
https://sci-hub.se/10.1111/j.1464-410X.2009.08538.x
“Archival formalin-fixed paraffin-embedded specimens from RPs (radical prostatectomy) and prostate biopsies were obtained. We used immunohistochemistry to investigate the activation level of five important markers of the mTOR pathway, including PTEN, p-Akt, p-mTOR, p-p70S6K and p-4E-BP1, in tissues from 182 patients with prostate cancer, 20 with benign prostatic hyperplasia (BPH) and 10 with high-grade prostatic intraepithelial neoplasia (HGPIN). The expression levels of these five markers were associated with patient clinical and pathological characteristics. The p-4E-BP1and p-p70S6K expression levels in primary cancer lesions were statistically significantly correlated with patient T stage and distant metastases. These results confirmed the activation cascade of the Akt/mTOR/4E-BP1/p70S6K pathway in prostate cancer. In the present study, the increased expression level of these four markers was apparent in the preneoplastic lesion HGPIN, which suggested that activation of this pathway might be an early event in prostate carcinogenesis. All these findings suggest that phosphorylation of 4E-BP1 and p70S6K by Akt/mTOR pathway might lead to protein synthesis, cell proliferation, cell-cycle progression, and increased invasive and metastatic ability of various cancer cells, including prostate cancer. In conclusion, using simple and reproducible immunohistochemical staining, most patients with prostate cancer had at least one component of the mTOR signalling pathway activated. The notion of using mTOR inhibitors as an additional treatment for patients with prostate cancer and a highly activated mTOR pathway is reasonable, and should be evaluated in future clinical trials.”
So here we have actual tissue markers (albeit hard to obtain). But we’re talking of extending lifespan…by default it SHOULD be extremely difficult yes? Lifespan is not going to just reveal itself so easily by just popping a pill? Now that is wishful thinking.
A 2021 trial using low dose rapamycin:
Phase I Trial of Encapsulated Rapamycin in Patients with Prostate Cancer Under Active Surveillance to Prevent Progression
“No approved medical therapies prevent progression of low grade prostate cancer. Rapamycin inhibits cell proliferation and augments immune responses, producing an antitumor effect.”
Only 1st 6 months reported (safety study). But they are just going to measure disease progression likely by PSA, biopsies …but why not measure mTOR TISSUE markers with biopsy samples?
I’ll gladly sign up for a tissue biopsy for tissue marker analysis…IF I could peer inside and look at the efficacy of my rapamycin dosing protocol. But this is a gargantuan ask. But so is the objective.
What are you a piece of Wagyu? Seriously wish you had a pre/post DEXA to share!
Had these mice gained weight since adulthood?
Right ok.
FWIW my body weight dropped from 78 to 72kg off 6mg per week of Rapamune (possibly more bio available than other forms) whilst my strength (relative and absolute) increased.
I had about a 12 lb weight loss with rapamycin and it’s maintained.
Humans have a genetic set point for their weight which makes it very difficult to budge. We can compensate for even vigorous exercise and our weight will remain stable.
I have triathletes who can’t lose weight and just remain at their set point. Not sure that the same is true in other species.
If only Rapamycin as causative, then modicum of signal concordance weight and strength
Eat less. That’s not genetic.
“You’d think at least some people would be reporting significant weight loss? Thus, my grand reservations.”
Since I had already reached my desired weight using time-restricted feeding, diet, and exercise, I can’t report that it induced weight loss, but I think it might because I have had an almost complete loss of appetite since taking rapamycin for several months and I have to force myself to eat enough food to maintain my desired weight.
I wonder if anyone else has had decreased appetite since taking rapamycin.
Actually, loss of appetite is not the correct term. The fact is: that I am rarely hungry.
Great points! Yes, we need human data. I have not looked at CR literature in awhile on longevity, but 20 years ago there was a depression risk noted with it. Is that still a thing?
Pic in spring 2020. hadn’t started rapamycin
You definitely look leaner…not only your arm but upper chest vs a recent similar regional pic. Whether you are a total whole body lower lean mass vs prior Rapamycin, that would have been interesting parameter. But you look amazing currently at 64. If you’re going to want to follow lean mass over time (new interventions, aging) do a baseline DEXA.
Thanks young guy!
I was at 196 pounds… shooting for 200 pounds once in my life… so close and then rapamycin started to shred any extra adipose tissue - fat!
Stuck at 180 pounds now… and very shredded compared to before… for me it was the rapamycin… only additional thing in the past 2 years.
Definitely getting my DEXA next… live pretty rural so need to find hospital or clinic that does bone, fat, muscle scan… my local hospital has a new scanner but only has software for bones? Cheez!!
Trying to keep up with you! And then you added the hair stack too…sucking wind.
I am quite happy with the weight loss. I have lost 5 lbs in 2 weeks on Rapa. The best part was I ate like crap during this time and still lost weight (It was international cheesecake week at the Cheesecake Factory - went there twice with family). I hope it continues. Thank you rapamycin!
I know, I know. Why did I do this? At least I convinced them not to go three times in a row. Although we did take cheesecake home for the next day. My family is not as health conscious… 
Love those guns, Agetron! Are you going to be the forum representative model?
“It was international cheesecake week at the Cheesecake Factory - went there twice with family”
Dang! I didn’t know that or I would have been there too. Don’t feel bad.
Auntie Mame says: " Life is a banquet, and most poor suckers are starving to death!"
Hahaha… I guess they will do for a 64 year old fart! If I can hover at this size another decade… won’t complain.
I am starting to believe that many people here cannot see the benefits of certain interventions (supplements, dietary changes, etc…) because they are too healthy! I am definitely not there (working on it though). However, I seem to see outsized gains when I do adopt a new strategy. I am thinking that this is because I am coming from a place of being not as healthy as the rest of you! However, it does run the risk of us discounting a strategy that may be useful to others even though it may not move our health needle.
Solution: We need more unhealthy guinea pigs… I mean volunteers to try new things!
Could be some truth to that. Seems like everyone is very health conscious and very likely not representative of the average person.
If you’re bed ridden it’s a huge step up in health just to get in a chair.
There is some merit to what you are saying…it’s all in the control reference point.
One of the big criticisms of mice studies is the “AD LIBITUM (AL)” control mice. This artificial construct results in lower longevity control mice, and thus inflates an intervention. For example, wild type mice NEVER feed ad libitum in the wild…so it’s ridiculous to call them “wild type”. They are only referenced as wild because they are a natural strain, not transgenic. NOT because of their dietary feeding habits.
So you have this wild type mouse eating massive quantities of food, outside it’s evolutionary history, ramping up all manner of aging pathways…they die YOUNG.
So then you overlay an intervention that say lowers food intake or other appetite dysregulation…and voila, the intervention looks amazing…relative to the control.
The basic premise of control fed mice is ERRONEOUS.
Makes you wonder about the biggest lifespan intervention in mice…CR. The intervention is all about restricting calories relative to AL mice?
Thus, this could explain a significant issue with human translation impact. The effect is much larger in mice, and humans have a tightly controlled set point that is much harder to shift to a new homeostasis.
Great! We are all here to listen and learn and improve.
