title: Transcriptional profiling reveals protective mechanisms in brains of long-lived mice.
abstract: The brain plays a central role in organismal aging but is itself most sensitive to aging-related functional impairments and pathologies. Insights into processes underlying brain aging are the basis to positively impact brain health. Using high-throughput RNA sequencing and quantitative polymerase chain reaction (PCR), we monitored cerebral gene expression in mice throughout their whole lifespan (2, 9, 15, 24, and 30 months). Differentially expressed genes were clustered in 6 characteristic temporal expression profiles, 3 of which revealed a distinct change between 24 and 30 months, the period when most mice die. Functional annotation of these genes indicated a participation in protection against cancer and oxidative stress. Specifically, the most enriched pathways for the differentially expressed genes with higher expression at 30 versus 24 months were found to be glutathione metabolism and chemokine signaling pathway, whereas those lower expressed were enriched in focal adhesion and pathways in cancer. We therefore conclude that brains of very old mice are protected from certain aspects of aging, in particular cancer, which might have an impact on organismal health and lifespan.
authors.affiliation: Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany. Electronic address: christiane.frahm@med.uni-jena.de.
authors.forename: Christiane
authors.initials: C
authors.lastname: Frahm
authors.affiliation: Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany.
authors.forename: Akash
authors.initials: A
authors.lastname: Srivastava
authors.affiliation: Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany.
authors.forename: Silvio
authors.initials: S
authors.lastname: Schmidt
authors.affiliation: Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany.
authors.forename: Jule
authors.initials: J
authors.lastname: Mueller
authors.affiliation: Genome Analysis, Leibniz Institute on Aging-Fritz Lipmann Institute, Jena, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Groth
authors.affiliation: Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany.
authors.forename: Madlen
authors.initials: M
authors.lastname: Guenther
authors.affiliation: Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Ji
authors.affiliation: Systems Biology and Bioinformatics, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Jena, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Priebe
authors.affiliation: Genome Analysis, Leibniz Institute on Aging-Fritz Lipmann Institute, Jena, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Platzer
authors.affiliation: Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany.
authors.forename: Otto W
authors.initials: OW
authors.lastname: Witte
mesh_terms: D000375:Aging / Q000235:genetics* / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000502:physiology*; D018925:Chemokines; D005978:Glutathione / Q000378:metabolism; D059014:High-Throughput Nucleotide Sequencing; D053208:Kaplan-Meier Estimate; D008297:Male; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000235:genetics; D018384:Oxidative Stress / Q000235:genetics; D016133:Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D013702:Temporal Lobe / Q000378:metabolism; D059467:Transcriptome
chemical_list: D018925:Chemokines; D005978:Glutathione
keywords: Aging; Brain; Cancer; Glutathione; RNA-seq; Survival curve