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rapamycin [2019/07/29 17:19] – [Collaborators] 89.187.177.110rapamycin [2019/07/29 18:46] (current) – [DNA methylation analysis] admin
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 ====== Rapamycin effects on aging-associated pathologies ====== ====== Rapamycin effects on aging-associated pathologies ======
  
-===== Objectives ===== 
  
-[[https://en.wikipedia.org/wiki/Sirolimus|Rapamycin]] is an inhibitor of the [[https://en.wikipedia.org/wiki/MTOR|mTOR]] pathway, which has been used in preventing rejection of solid organ allografts. In this multi-PI study on an older age healthy human cohort, we assess the usability and efficacy of Rapamycin in improving physical performance, cardiac and vascular health, and immune outcomes. This approach is motivated by the promising results that were observed in prior studies on mice models. Oncinfo contributes in this study through analysis of gene expression and DNA methylation profiles.+===== Objectives =====
  
 +[[https://en.wikipedia.org/wiki/Sirolimus|Rapamycin]] is an inhibitor of the [[https://en.wikipedia.org/wiki/MTOR|mTOR]] pathway and it has been used in preventing rejection of solid organ allografts. In this multi-PI study on an older age healthy human cohort, we assess the usability and efficacy of Rapamycin in improving physical performance, cardiac and vascular health, and immune outcomes. This approach is motivated by the promising results that were observed in prior studies on mice models. Oncinfo contributes in this study through analysis of gene expression and DNA methylation profiles.
  
 ===== Data ===== ===== Data =====
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 ===== Collaborators ===== ===== Collaborators =====
  
-Dr. [[https://wp.uthscsa.edu/mimg/team-member/ellen-kraig-ph-d/|Ellen Kraig]], an immunologist from the University of Texas Health Science Center at San Antonio.+Dr. [[https://wp.uthscsa.edu/mimg/team-member/ellen-kraig-ph-d/|Ellen Kraig]], an immunologist, and Dr. [[https://www.uthscsa.edu/academics/biomedical-sciences/faculty/profile/0V71EU5IM/Kellogg,-Dean-L.-Jr.|Dean Kellogg]], a physiologist, both from the University of Texas Health Science Center at San Antonio.
  
-Dr. [[https://www.uthscsa.edu/academics/biomedical-sciences/faculty/profile/0V71EU5IM/Kellogg,-Dean-L.-Jr.|Dean Kellogg]], a physiologist from the University of Texas Health Science Center at San Antonio. 
  
 +===== DNA methylation analysis =====
  
-===== Subprojects =====+We follow the Bioconductor [[https://www.bioconductor.org/packages/release/workflows/vignettes/methylationArrayAnalysis/inst/doc/methylationArrayAnalysis.html#differential-methylation-analysis|workflow]] to identify the probes and regions that are differentially methylation due to Rapamycin treatment.
  
-  - Analyze only the PBMC samples (buccals can wait until we are deciding whether they would work better). 
-  - As there are few females and not the same number in the control groups, it may be beneficial to do two analyses: a) all subjects  and  b) just the male subjects. 
-  - There are really two questions to address: \\ a)   Do the POST-rapamycin samples differ from the PRE-rapamycin samples (for each of the subjects)? \\ b)    Is there an overall difference between the POST-rapamycin group and the POST-placebo group? \\ 4.   We do want to look at all of the methylation marks, but initially it may be worth interrogating genes/proteins known to be regulated either by methylation (DDAH2) or by rapamycin (foxp3, RAGE, soluble ICAM1). 
  
 ===== Related work ===== ===== Related work =====
  
-  - Niu, Pan-Pan, et al. "Hypermethylation of DDAH2 promoter contributes to the dysfunction of endothelial progenitor cells in coronary artery disease patients." [[https://translational-medicine.biomedcentral.com/articles/10.1186/1479-5876-12-170|Journal of translational medicine]] 12.1 (2014): 170. \\  Dean Kellogg mentioned that //DDAH2//  has already been shown to be regulated by methylation. However, Ellen doesn’t know its transcription state in PBMCs. +  - Kraig, Ellen, 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." [[https://www.sciencedirect.com/science/article/pii/S0531556517309130|Experimental gerontology]] 105 (2018): 53-69.
-  - Grönniger, Elke, et al. "Aging and chronic sun exposure cause distinct epigenetic changes in human skin." [[https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1000971|PLoS genetics]] 6.5 (2010): e1000971. +
-  - Pope, Arthur J., Kanchana Karuppiah, and Arturo J. Cardounel. "Role of the PRMT–DDAH–ADMA axis in the regulation of endothelial nitric oxide production." [[https://www.sciencedirect.com/science/article/pii/S1043661809002011?via=ihub|Pharmacological research]] 60.6 (2009): 461-465. +
-  - Kanjuh, V., et al. "1P-0066 Severity of coronary arterial stenotic changes correlates with increases in plasma insulin and plasminogen activator inhibitor 1 levels in patients with type 2 diabetes." [[https://www.sciencedirect.com/science/article/pii/S1567568803901413?via=ihub|Atherosclerosis]] 2.4 (2003): 33-34.+