Rapa is well tolerated

[TomBAvoider]

This is of course in a therapeutic setting, but in principle it shows that humans can tolerate rapa and even benefit from it - so it's 'proof of concept' to some degree:

https://prostatecancernewstoday.com/2020/02/17/erapa-leads-to-boost-in-immune-cells-in-low-grade-prostate-cancer-patients-phase-1b-data-suggest/

Daily treatment with a low dose of eRapa, Emtora Biosciences' new formulation of the therapeutic agent rapamycin, was safe and well tolerated, and led to immune system cell boosting in patients with low-grade prostate cancer, according to data from a Phase 1b clinical trial.

[Dean Pomerleau]

According to a new study [1] in Nature, Rapamycin appears not to be well tolerated in mice with relatively short telomeres:

Blocking nutrient sensing by treatment with rapamycin, an mTOR inhibitor, delays the aging of healthy mice, but curiously, it worsens diseases and premature aging that occur in mice with short telomeres.

--Dean 

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[1] Nature Communications volume 11, Article number: 1168 (2020) Cite

Free full text: https://www.nature.com/articles/s41467-020-14962-1#menu

The mTOR pathway is necessary for survival of mice with short telomeres

Iole Ferrara-Romeo, 

Paula Martinez, 

Sarita Saraswati, 

Kurt Whittemore, 

Osvaldo Graña-Castro, 

Lydia Thelma Poluha, 

Rosa Serrano, 

Elena Hernandez-Encinas, 

Carmen Blanco-Aparicio, 

Juana Maria Flores & 

Maria A. Blasco 

Abstract

Telomerase deficiency leads to age-related diseases and shorter lifespans. Inhibition of the mechanistic target of rapamycin (mTOR) delays aging and age-related pathologies. Here, we show that telomerase deficient mice with short telomeres (G2-Terc−/−) have an hyper-activated mTOR pathway with increased levels of phosphorylated ribosomal S6 protein in liver, skeletal muscle and heart, a target of mTORC1. Transcriptional profiling confirms mTOR activation in G2-Terc−/− livers. Treatment of G2-Terc−/− mice with rapamycin, an inhibitor of mTORC1, decreases survival, in contrast to lifespan extension in wild-type controls. Deletion of mTORC1 downstream S6 kinase 1 in G3-Terc−/− mice also decreases longevity, in contrast to lifespan extension in single S6K1−/− female mice. These findings demonstrate that mTOR is important for survival in the context of short telomeres, and that its inhibition is deleterious in this setting. These results are of clinical interest in the case of human syndromes characterized by critically short telomeres.