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Is Rapamycin the first step towards a longer life?

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Luis Almeida Nov 22, 2020

[1]Rožman, P., How Could We Slow or Reverse the Human Aging Process and Extend the Healthy Life Span with Heterochronous Autologous Hematopoietic Stem Cell Transplantation. Rejuvenation Res, 2020. 23(2): p. 159-170.

[2]Sehgal, S.N., H. Baker, and C. Vézina, Rapamycin (AY-22,989), a new antifungal antibiotic. II. Fermentation, isolation and characterization. J Antibiot (Tokyo), 1975. 28(10): p. 727-32.

[3]Laplante, M. and D.M. Sabatini, mTOR signaling in growth control and disease. Cell, 2012. 149(2): p. 274-93.

[4]Seto, B., Rapamycin and mTOR: a serendipitous discovery and implications for breast cancer. Clin Transl Med, 2012. 1(1): p. 29.

[5]Harrison, D.E., et al., Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature, 2009. 460(7253): p. 392-5.

[6]Kapahi, P., et al., Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway. Curr Biol, 2004. 14(10): p. 885-90.

[7]Vellai, T., et al., Genetics: influence of TOR kinase on lifespan in C. elegans. Nature, 2003. 426(6967): p. 620.

[8]Bitto, A., et al., Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice. 2016. 5.

[9]Kim, A., Wanted: 10,000 dogs for the largest-ever study on aging in canines, in CNN Health. 2019.

[10]Blagosklonny, M.V., Rapamycin for longevity: opinion article. Aging (Albany NY), 2019. 11(19): p. 8048-8067.

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2. Intermittent doses of Rapamycin

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Shubhankar Kulkarni
Shubhankar Kulkarni Nov 24, 2020

[1]Kraig E, Linehan LA, Liang H, Romo TQ, Liu Q, Wu Y, et al. A randomized control trial to establish the feasibility and safety of rapamycin treatment in an older human cohort: Immunological, physical performance, and cognitive effects. Exp Gerontol [Internet]. 2018 May;105:53–69. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0531556517309130

[2]Mannick JB, Morris M, Hockey H-UP, Roma G, Beibel M, Kulmatycki K, et al. TORC1 inhibition enhances immune function and reduces infections in the elderly. Sci Transl Med [Internet]. 2018 Jul 11;10(449):eaaq1564. Available from: https://stm.sciencemag.org/lookup/doi/10.1126/scitranslmed.aaq1564

[3]Arriola Apelo SI, Pumper CP, Baar EL, Cummings NE, Lamming DW. Intermittent Administration of Rapamycin Extends the Life Span of Female C57BL/6J Mice. Journals Gerontol Ser A Biol Sci Med Sci [Internet]. 2016 Jul;71(7):876–81. Available from: https://academic.oup.com/biomedgerontology/article-lookup/doi/10.1093/gerona/glw064

[4]Blagosklonny M V. Aging, Stem Cells, and Mammalian Target of Rapamycin: A Prospect of Pharmacologic Rejuvenation of Aging Stem Cells. Rejuvenation Res [Internet]. 2008 Aug;11(4):801–8. Available from: https://www.liebertpub.com/doi/10.1089/rej.2008.0722

3. Rapamycin eliminates hyper-immunity

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Shubhankar Kulkarni
Shubhankar Kulkarni Nov 24, 2020

[1]Svatek RS, Ji N, de Leon E, Mukherjee NZ, Kabra A, Hurez V, et al. Rapamycin Prevents Surgery-Induced Immune Dysfunction in Patients with Bladder Cancer. Cancer Immunol Res [Internet]. 2018 Dec 18; Available from: http://cancerimmunolres.aacrjournals.org/lookup/doi/10.1158/2326-6066.CIR-18-0336

[2]Mannick JB, Del Giudice G, Lattanzi M, Valiante NM, Praestgaard J, Huang B, et al. mTOR inhibition improves immune function in the elderly. Sci Transl Med [Internet]. 2014 Dec 24;6(268):268ra179-268ra179. Available from: https://stm.sciencemag.org/lookup/doi/10.1126/scitranslmed.3009892

[3]Keating R, Hertz T, Wehenkel M, Harris TL, Edwards BA, McClaren JL, et al. The kinase mTOR modulates the antibody response to provide cross-protective immunity to lethal infection with influenza virus. Nat Immunol [Internet]. 2013 Dec 20;14(12):1266–76. Available from: http://www.nature.com/articles/ni.2741

[4]Blagosklonny M V. Aging and Immortality: Quasi-Programmed Senescence and Its Pharmacologic Inhibition. Cell Cycle [Internet]. 2006 Sep 15;5(18):2087–102. Available from: https://www.tandfonline.com/doi/full/10.4161/cc.5.18.3288

[5]Blagosklonny M V. Rapamycin for longevity: opinion article. Aging (Albany NY) [Internet]. 2019 Oct 4;11(19):8048–67. Available from: http://www.aging-us.com/article/102355/text

4. TOR is beneficial early and damaging later on in life

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Shubhankar Kulkarni
Shubhankar Kulkarni Nov 24, 2020

[1]Demidenko ZN, Blagosklonny M V. Growth stimulation leads to cellular senescence when the cell cycle is blocked. Cell Cycle [Internet]. 2008 Nov 5;7(21):3355–61. Available from: http://www.tandfonline.com/doi/abs/10.4161/cc.7.21.6919

[2]Murakami M, Ichisaka T, Maeda M, Oshiro N, Hara K, Edenhofer F, et al. mTOR Is Essential for Growth and Proliferation in Early Mouse Embryos and Embryonic Stem Cells. Mol Cell Biol [Internet]. 2004 Aug 1;24(15):6710–8. Available from: https://mcb.asm.org/content/24/15/6710

[3]Murakami M, Ichisaka T, Maeda M, Oshiro N, Hara K, Edenhofer F, et al. mTOR Is Essential for Growth and Proliferation in Early Mouse Embryos and Embryonic Stem Cells. Mol Cell Biol [Internet]. 2004 Aug 1;24(15):6710–8. Available from: https://mcb.asm.org/content/24/15/6710

[4]Blagosklonny M V. Aging: ROS or TOR. Cell Cycle [Internet]. 2008 Nov 5;7(21):3344–54. Available from: http://www.tandfonline.com/doi/abs/10.4161/cc.7.21.6965

mTOR is involved in biosynthesis of lipids and related to telomeres

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Brett M.
Brett M. Nov 25, 2020

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General comments

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Povilas S
Povilas S2 months ago
Thanks for an interesting and informative summary about the drug. I got immediately hooked up due to the fact that it was first discovered on Eastern Island, which is mysterious on its own and is often speculated to have connections with aliens. So the life-prolonging drug produced by local bacteria fits the picture and makes it even more interesting. I wonder if that species of bacteria is only found there or in other places too. There's a lot of info about the drug but very little about the bacteria itself.
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Darko Savic
Darko Savic2 months ago
Povilas Sway to introduce pseudoscience to the platform:)
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Povilas S
Povilas S2 months ago
Darko Savic Yes, I thought about that. But there are two sides to this - pseudoscience and similar topics are naturally interesting to people and might get you fired up about researching the topic more seriously, that's exactly what happened - I then researched about the drug, the bacteria, all the scientific stuff that I wasn't motivated to do before, even though I saw the drug mentioned a few times in other sessions. And that's all because he mentioned Easter Island and the etymology of the drug name, a few interesting facts.
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Darko Savic
Darko Savic2 months ago
Once we do figure out how Rapamycin leads to slower aging maybe derivatives (rapalogs) will be the way to minimize side effects while retaining the benefits