title: Mice fed rapamycin have an increase in lifespan associated with major changes in the liver transcriptome.
abstract: Rapamycin was found to increase (11% to 16%) the lifespan of male and female C57BL/6J mice most likely by reducing the increase in the hazard for mortality (i.e., the rate of aging) term in the Gompertz mortality analysis. To identify the pathways that could be responsible for rapamycin's longevity effect, we analyzed the transcriptome of liver from 25-month-old male and female mice fed rapamycin starting at 4 months of age. Few changes (<300 transcripts) were observed in transcriptome of rapamycin-fed males; however, a large number of transcripts (>4,500) changed significantly in females. Using multidimensional scaling and heatmap analyses, the male mice fed rapamycin were found to segregate into two groups: one group that is almost identical to control males (Rapa-1) and a second group (Rapa-2) that shows a change in gene expression (>4,000 transcripts) with more than 60% of the genes shared with female mice fed Rapa. Using ingenuity pathway analysis, 13 pathways were significantly altered in both Rapa-2 males and rapamycin-fed females with mitochondrial function as the most significantly changed pathway. Our findings show that rapamycin has a major effect on the transcriptome and point to several pathways that would likely impact the longevity.
authors.affiliation: Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.
authors.forename: Wilson C
authors.initials: WC
authors.lastname: Fok
authors.affiliation: Department of Epidemiology & Biostatistics, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America ; Greehey Children's Cancer Research Institute, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America ; Cancer Therapy and Research Center, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.
authors.forename: Yidong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America ; Department of Epidemiology & Biostatistics, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.
authors.forename: Alex
authors.initials: A
authors.lastname: Bokov
authors.affiliation: Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America ; Department of Physiology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.
authors.forename: Yiqiang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America ; Department of Molecular Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America ; Research Service and Geriatric Research Education and Clinical Center, Audie Murphy VA Hospital (STVHCS), San Antonio, Texas, United States of America.
authors.forename: Adam B
authors.initials: AB
authors.lastname: Salmon
authors.affiliation: Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.
authors.forename: Vivian
authors.initials: V
authors.lastname: Diaz
authors.affiliation: Department of Psychiatry, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.
authors.forename: Martin
authors.initials: M
authors.lastname: Javors
authors.affiliation: National Institute on Aging, Baltimore, Maryland, United States of America.
authors.forename: William H
authors.initials: WH
authors.lastname: Wood
authors.affiliation: National Institute on Aging, Baltimore, Maryland, United States of America.
authors.forename: Yongqing
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: National Institute on Aging, Baltimore, Maryland, United States of America.
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Becker
authors.affiliation: Linus Pauling Institute, Department of Biochemistry and Biophysics, Oregon State University, Corvallis, Oregon, United States of America.
authors.forename: Viviana I
authors.initials: VI
authors.lastname: Pérez
authors.affiliation: Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America ; Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America ; Research Service and Geriatric Research Education and Clinical Center, Audie Murphy VA Hospital (STVHCS), San Antonio, Texas, United States of America.
authors.forename: Arlan
authors.initials: A
authors.lastname: Richardson
mesh_terms: D000818:Animals; D016000:Cluster Analysis; D004032:Diet; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008136:Longevity / Q000235:genetics*; D008297:Male; D051379:Mice; D012737:Sex Factors; D015398:Signal Transduction; D020123:Sirolimus / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D059467:Transcriptome
chemical_list: D020123:Sirolimus