Rapamycin is looked at a lot in longevity research. So if rapamycin helps help height growth then it could be a supplement worth looking into. Previously looking into mtor and rapamycin showed that rapamycin made bone growth slower. However, it is conceivable that rapamycin may make bone growth slower but increase height at skeletal maturity. Although based on the information presented in the study it seems that rapamycin can not increase long bone growth
“the role of mTOR signaling in three aspects of tetrapod limb development: 1) limb outgrowth; 2) chondrocyte differentiation after mesenchymal condensation and 3) endochondral ossification-driven longitudinal bone growth. We conclude that, given its ability to interact with the most common signaling pathways, its presence in multiple cell types, and its ability to influence cell proliferation, size and differentiation, the mTOR pathway is a critical integrator of external stimuli and internal status, coordinating developmental transitions as complex as those taking place during limb development.”
“mTOR stands for mechanistic (formerly mammalian) target of rapamycin, a macrolide produced by Streptomyces Hygroscopicus bacteria. Rapamycin was named after the island of Rapa Nui, where it was discovered in the early 1990 s during a genetic screen in the budding yeast, where TOR1 and TOR2 were identified as the toxic agents of rapamycin”
“mTORC1 signaling in the limb mesenchyme is required for the normal size of both the limb bud and its individual cells, but relatively dispensable for skeletal patterning”
“MPs have been shown to induce mTORC1 activation via the ALK3 receptor and Smad4-mediated inhibition of PTEN. mTORC1, in turn, is required for the translational control of SOX9, a key transcription factor in the progression towards cartilage. mTORC1 has been shown to upregulate HIF-1α protein levels in the cartilage, which is critical for the control of glucose metabolism, proliferation and differentiation in chondrocytes”
“mTORC1 inhibition impaired fetal chondrocyte differentiation and response to insulin, but not proliferation. Similarly, genetic deletion of either Mtor or Raptor in the mouse cartilage impaired skeletal growth through reduced matrix production, decreased chondrocyte size and delayed chondrocyte hypertrophy”
“The size of the proliferative zone is controlled by a well characterized negative feedback loop between IHH and PTHrP. In this loop, IHH produced by pre-hypertrophic chondrocytes induces PTHrP expression in resting chondrocytes, whereas PTHrP secreted from the resting zone promotes chondrocyte proliferation and delays differentiation, including Ihh expression. mTOR is likely involved in this feedback loop in two different ways: via mechanotransduction-dependent Ihh expression, and via regulation of PTHrP signaling. Regarding the former, mechanical loading is an important regulator of chondrocyte maturation, and experiments in chicken embryos showed that elimination of muscle contraction results in mTOR inhibition in the cartilaginous growth plate”
“On the other hand, mTORC1 activation has been shown to reduce expression of the PTHrP receptor in articular cartilage, which could potentially happen in the growth plate cartilage as well{perhaps it is thus mechanisms by which rapamycin could potentially increase height at skeletal maturity?}. S6K1, a downstream effector of mTORC1, phosphorylates and allows nuclear translocation of HH-signaling transducer GLI2, leading to transcription of Pthlh, encoding PTHrP. The mTOR/PTHrP interaction also works in reverse. Studies of skeletal dysplasia syndromes characterized by constitutive activation of PTH/PTHrP showed reduced activities of salt inducible kinase 3 (SIK3), which caused accumulation of DEPTOR, in turn inhibiting mTORC1 and 2 activity, biasing skeletal progenitor differentiation towards fat instead of bone. This new PTH/PTHrP-SIK3-mTOR axis has been recently explored further, showing that, in the presence of nutrients, DEPTOR directly interacts with PTH1R to regulate PTH/PTHrP signaling, whereas in the absence of nutrients it forms a complex with TAZ (an effector of the Hippo pathway), to prevent its translocation to the nucleus and therefore inhibit its transcriptional activity”
“Wnt10b overexpression causes enlargement of calvarial tissue and phosphorylation of S6, both of which effects were abrogated by rapamycin”<-obviously we want enlargement so rapamycin in that case is bad.