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Prescription Drug Rapamycin: Its Impact on Aging and Longevity

Rapamycin Longevity

Rapamycin, a macrolide antibiotic drug derived from the bacterial species, Streptomyces hygroscopicus, has the potential to extend longevity and improve overall health by targeting the mammalian target of rapamycin (mTOR) pathway. Studies have suggested that rapamycin may be beneficial for general health and longevity, but there are risks associated with its use including immunosuppression, glucose intolerance and altered lipid metabolism. Further research is needed to understand its long-term effects in humans. 

Rapamycin, a macrolide antibiotic drug derived from the bacterium Streptomyces hygroscopicus, has been gaining considerable attention in recent years for its potential to extend longevity and improve overall health. In animal models, rapamycin has been found to extend lifespan by up to 30% (Harrison et al., 2009; Miller et al., 2014; Strong et al. 2020), reduce age-related diseases, and protect against cancer, diabetes and neurodegeneration ). Additionally, studies have indicated that rapamycin may also be beneficial for cardiovascular health and cognitive function (Amin et al., 2019; Nguyen et al., 2021). However, it is important to note that there are still many unknowns regarding long-term safety and efficacy of rapamycin as an anti-aging therapy.

The primary mechanism through which rapamycin confers its beneficial effects is by targeting the mammalian target of rapamycin (mTOR) pathway, a key regulator of cell growth, metabolism and longevity. Activation of this pathway leads to increased cellular stress and protein synthesis, while inhibition of mTOR has been found to decrease oxidative damage and improve autophagy (self-digestion) of damaged proteins and organelles (Arab et al., 2022; Ma et al., 2021). Rapamycin inhibits the mTOR pathway, resulting in decreased cell growth and increased lifespan (Bjedov & Rallis, 2020).

Although rapamycin has demonstrated promise in animal models, its potential for use in humans is still somewhat uncertain. Studies of rapamycin in humans have focused primarily on its ability to suppress immune responses in transplant patients (Allison, 2016; Bauer et al., Chang et al., 1991). While some studies have suggested that rapamycin may be beneficial for general health and longevity, the evidence is limited and further research is needed.

In addition to its potential benefits, there are also risks associated with rapamycin use. The most serious side effect of rapamycin is immunosuppression, which can increase the risk of infection. There is also concern that long-term use of rapamycin may be associated with adverse metabolic effects, such as glucose intolerance and altered lipid metabolism (Johnson & Kaeberlein, 2016; Salmon, 2015; Soefje et al., 2011). Furthermore, rapamycin has been found to affect fertility in male mice (Oliveira et al., 2017), although it is unclear whether this effect would be seen in humans.

In conclusion, rapamycin has demonstrated potential as an anti-aging therapy, but further research is needed to understand its long-term effects in humans. The potential benefits of rapamycin may outweigh the risks, but caution should be taken when considering its use as an anti-aging supplement.

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References

  1. Amin, S., Lux, A., & O’Callaghan, F. (2019). The journey of metformin from glycaemic control to mTOR inhibition and the suppression of tumour growth. British journal of clinical pharmacology, 85(1), 37–46. https://doi.org/10.1111/bcp.13780
  2. Arab, H. H., Ashour, A. M., Eid, A. H., Arafa, E. A., Al Khabbaz, H. J., & Abd El-Aal, S. A. (2022). Targeting oxidative stress, apoptosis, and autophagy by galangin mitigates cadmium-induced renal damage: Role of SIRT1/Nrf2 and AMPK/mTOR pathways. Life sciences, 291, 120300. https://doi.org/10.1016/j.lfs.2021.120300
  3. Bauer, A. C., Franco, R. F., & Manfro, R. C. (2020). Immunosuppression in Kidney Transplantation: State of the Art and Current Protocols. Current pharmaceutical design, 26(28), 3440–3450. https://doi.org/10.2174/1381612826666200521142448
  4. Bjedov, I., & Rallis, C. (2020). The Target of Rapamycin Signalling Pathway in Ageing and Lifespan Regulation. Genes, 11(9), 1043. https://doi.org/10.3390/genes11091043
  5. Chang, J. Y., Sehgal, S. N., & Bansbach, C. C. (1991). FK506 and rapamycin: novel pharmacological probes of the immune response. Trends in pharmacological sciences, 12(6), 218–223. https://doi.org/10.1016/0165-6147(91)90555-7
  6. Harrison, D. E., Strong, R., Sharp, Z. D., Nelson, J. F., Astle, C. M., Flurkey, K., Nadon, N. L., Wilkinson, J. E., Frenkel, K., Carter, C. S., Pahor, M., Javors, M. A., Fernandez, E., & Miller, R. A. (2009). Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature, 460(7253), 392–395. https://doi.org/10.1038/nature08221
  7. Johnson, S. C., & Kaeberlein, M. (2016). Rapamycin in aging and disease: maximizing efficacy while minimizing side effects. Oncotarget, 7(29), 44876–44878. https://doi.org/10.18632/oncotarget.10381
  8. Ma, Z., Zhang, W., Wu, Y., Zhang, M., Wang, L., Wang, Y., Wang, Y., & Liu, W. (2021). Cyclophilin A inhibits A549 cell oxidative stress and apoptosis by modulating the PI3K/Akt/mTOR signaling pathway. Bioscience reports, 41(1), BSR20203219. https://doi.org/10.1042/BSR20203219
  9. Miller, R. A., Harrison, D. E., Astle, C. M., Fernandez, E., Flurkey, K., Han, M., Javors, M. A., Li, X., Nadon, N. L., Nelson, J. F., Pletcher, S., Salmon, A. B., Sharp, Z. D., Van Roekel, S., Winkleman, L., & Strong, R. (2014). Rapamycin-mediated lifespan increase in mice is dose and sex dependent and metabolically distinct from dietary restriction. Aging cell, 13(3), 468–477. https://doi.org/10.1111/acel.12194
  10. Nguyen, S., Banks, W. A., & Rhea, E. M. (2021). Effects of Rapamycin on Insulin Brain Endothelial Cell Binding and Blood-Brain Barrier Transport. Medical sciences (Basel, Switzerland), 9(3), 56. https://doi.org/10.3390/medsci9030056
  11. Oliveira, P. F., Cheng, C. Y., & Alves, M. G. (2017). Emerging Role for Mammalian Target of Rapamycin in Male Fertility. Trends in endocrinology and metabolism: TEM, 28(3), 165–167. https://doi.org/10.1016/j.tem.2016.12.004
  12. Salmon AB. About-face on the metabolic side effects of rapamycin. Oncotarget. 2015 Feb 20;6(5):2585-6. doi: 10.18632/oncotarget.3354. PMID: 25691064; PMCID: PMC4413601.
  13. Soefje, S. A., Karnad, A., & Brenner, A. J. (2011). Common toxicities of mammalian target of rapamycin inhibitors. Targeted oncology, 6(2), 125–129. https://doi.org/10.1007/s11523-011-0174-9
  14. Strong, R., Miller, R. A., Bogue, M., Fernandez, E., Javors, M. A., Libert, S., Marinez, P. A., Murphy, M. P., Musi, N., Nelson, J. F., Petrascheck, M., Reifsnyder, P., Richardson, A., Salmon, A. B., Macchiarini, F., & Harrison, D. E. (2020). Rapamycin-mediated mouse lifespan extension: Late-life dosage regimes with sex-specific effects. Aging cell, 19(11), e13269. https://doi.org/10.1111/acel.13269

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