{
  "titles": [
    "2018 -  Mechanisms of Vascular Aging.pdf",
    "2016 - The dog aging project translational geroscience in companion.pdf",
    "2015 - Cellular and Molecular Biology of Aging Endothelial Cells.pdf",
    "2012 - Aging, Rejuvenation, and Epigenetic.pdf",
    "2020 - Clinical Genetics and Genomics of Aging.pdf",
    "2020 - Clinical Genetics and Genomics of Aging.pdf",
    "2015 - Cellular and Molecular Biology of Aging Endothelial Cells.pdf",
    "2017 - Epigenetic aging signatures in mice livers.pdf",
    "2017 - Diverse interventions that extend mouse.pdf",
    "2020 - Clinical Genetics and Genomics of Aging.pdf"
  ],
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    "168. Yin L, Ye S, Chen Z, Zeng Y . Rapamycin preconditioning attenuates tran- sient focal cerebral ischemia/reperfusion injury in mice. Int J Neurosci. 2012;122:748756. doi: 10.3109/00207454.2012.721827  169. Spilman P, Podlutskaya N, Hart MJ, Debnath J, Gorostiza O, Bredesen  D, Richardson A, Strong R, Galvan V . Inhibition of mTOR by rapamy-cin abolishes cognitive deficits and reduces amyloid-beta levels in a  mouse model of Alzheimers disease. PLoS One. 2010;5:e9979. doi:  10.1371/journal.pone.0009979",
    "Anisimov VN, Zabezhinski MA, Popovich IG, Piskunova TS, Semenchenko AV, Tyndyk ML, Yurova MN, Rosenfeld SV,Blagosklonny MV (2011b) Rapamycin increases lifespan and inhibits spontaneous tumorigenesis in inbred female mice. Cell Cycle 10:42304236 Augustine JJ, Bodziak KA, Hricik DE (2007) Use of sirolimus in solid organ transplantation. Drugs 67:369391 Bannister CA, Holden SE, Jenkins-Jones S, Morgan CL, Halcox JP,",
    "ACCEPTED MANUSCRIPTACCEPTED MANUSCRIPT mTOR complex 2 (mTORC2), the less clearly identified  and less sensitive to rapamycin. Most information to  date on the r ole of mTOR has studied the insulin/nutrient signaling via the mTORC1 and significantly less in  known about the role of mTORC2 ( in this review, future references measure either mTORC1 or general mTOR  activity )[251]. Earlier this decade studies showed that decreasing TOR signaling, genetically or with rapamycin,",
    "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., et al. (2009). Rapamycin Cell148, January 20, 2012 2012 Elsevier Inc. 55",
    "96. Lamming DW, Ye L, Katajisto P, Goncalves MD, Saitoh M, Stevens DM, etal. Rapamycin-  induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity.  Science. 2012;335:163843.  97. Tataranni T, Biondi G, Cariello M, Mangino M, Colucci G, Rutigliano M, etal. Rapamycin-  induced hypophosphatemia and insulin resistance are associated with mTORC2 activation  and klotho expression. Am J Transplant. 2011;11(8):165664.",
    "ing these aspects in future studies on the effects of resveratrol could help to study in  greater depth the mechanisms of action of this compound [56].  Rapamycin Rapamycin is a macrolide isolated from Streptomyces hygroscopicus, a bacteria  from Pascua Island (Rapa Nui). It has functions as an antibiotic, an immune sup- pressant drug, and it is also proposed as a CRM.After the first studies, it was found  that rapamycin could induce the extension of the replicative life of yeast through the",
    "[257] Wilkinson JE, Burmeister L, Brooks SV, Chan CC, Friedline S, Harrison DE, et al. Rapamycin slows  aging in mi ce. Aging Cell. 2012;11:675 -82.  [258] Selman C, Tullet JM, Wieser D, Irvine E, Lingard SJ, Choudhury AI, et al. Ribosomal protein S6 kinase 1  signaling regulates mammalian life span. Science. 2009;326:140 -4.  [259] Reihl K, Seals D, Henson G, LaRocca T, Mag erko K, Bosshardt G, et al. Dietary rapamycin selectively  improves arterial function in old mice. FASEB Journal. 2013;27:1194.17.",
    "29. Wilkinson JE, Burmeister L, Brooks SV, Chan C-C, Friedline S, Harrison DE, et al. Rapamycin slows aging in mice. Aging Cell. 2012;11:675 82. 30. Lamming DW, Ye L, Katajisto P, Goncalves MD, Saitoh M, Stevens DM, et al. Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity. Science. 2012;335:1638 43. 31. Zampieri M, Ciccarone F, Calabrese R, Franceschi C, Brkle A, Caiafa P. Reconfiguration of DNA methylation in aging. Mech Ageing Dev. 2015;151:60 70.",
    "files [55, 62]. Of note, rapamycin in particular appears to induce additional changes u nrelated to age-associated changes. While both CR and rapamycin induced these non-age-related effects, this effect was much more marked for rapamycin. These non age-related epigenetic changes include gains of methylation at genes, enhancers and CpG islands and losses of methylation at genes and enhancers. Conceivably, such non age-related effects of rapamycin in",
    "23  94. Chakrabarti P, English T, Shi J, Smas CM, Kandror KV .Mammalian target of rapamycin  complex 1 suppresses lipolysis, stimulates lipogenesis, and promotes fat storage. Diabetes.  2010;59:77581.  95. Miller RA, Harrison DE, Astle CM, Fernandez E, Flurkey K, Han M, et al. Rapamycin-  mediated lifespan increase in mice is dose and sex dependent and metabolically distinct from  dietary restriction. Aging Cell. 2014;13:46877."
  ],
  "answer": "Here are the studies that include rapamycin:  1. **Yin L, Ye S, Chen Z, Zeng Y (2012)**: \"Rapamycin preconditioning attenuates transient focal cerebral ischemia/reperfusion injury in mice\" [1]. 2. **Spilman P, Podlutskaya N, Hart MJ, Debnath J, Gorostiza O, Bredesen D, Richardson A, Strong R, Galvan V (2010)**: \"Inhibition of mTOR by rapamycin abolishes cognitive deficits and reduces amyloid-beta levels in a mouse model of Alzheimer's disease\" [1]. 3. **Anisimov VN, Zabezhinski MA, Popovich IG, Piskunova TS, Semenchenko AV, Tyndyk ML, Yurova MN, Rosenfeld SV, Blagosklonny MV (2011)**: \"Rapamycin increases lifespan and inhibits spontaneous tumorigenesis in inbred female mice\" [2]. 4. **Lamming DW, Ye L, Katajisto P, Goncalves MD, Saitoh M, Stevens DM, et al. (2012)**: \"Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity\" [5]. 5. **Tataranni T, Biondi G, Cariello M, Mangino M, Colucci G, Rutigliano M, et al. (2011)**: \"Rapamycin-induced hypophosphatemia and insulin resistance are associated with mTORC2 activation and klotho expression\" [5]. 6. **Wilkinson JE, Burmeister L, Brooks SV, Chan CC, Friedline S, Harrison DE, et al. (2012)**: \"Rapamycin slows aging in mice\" [7]. 7. **Reihl K, Seals D, Henson G, LaRocca T, Magerko K, Bosshardt G, et al. (2013)**: \"Dietary rapamycin selectively improves arterial function in old mice\" [7]. 8. **Miller RA, Harrison DE, Astle CM, Fernandez E, Flurkey K, Han M, et al. (2014)**: \"Rapamycin-mediated lifespan increase in mice is dose and sex dependent and metabolically distinct from dietary restriction\" [10].  These references provide a comprehensive list of studies involving rapamycin.",
  "question": "List as many studies as you can that include rapamycin."
}