title: MicroRNA miR-29 controls a compensatory response to limit neuronal iron accumulation during adult life and aging.
abstract: A widespread modulation of gene expression occurs in the aging brain, but little is known as to the upstream drivers of these changes. MicroRNAs emerged as fine regulators of gene expression in many biological contexts and they are modulated by age. MicroRNAs may therefore be part of the upstream drivers of the global gene expression modulation correlated with aging and aging-related phenotypes.
  
  
  
  Here, we show that microRNA-29 (miR-29) is induced during aging in short-lived turquoise killifish brain and genetic antagonism of its function induces a gene-expression signature typical of aging. Mechanicistically, we identified Ireb2 (a master gene for intracellular iron delivery that encodes for IRP2 protein), as a novel miR-29 target. MiR-29 is induced by iron loading and, in turn, it﻿﻿ reduces IRP2 expression in vivo, therefore limiting intracellular iron delivery in neurons. Genetically modified fish with neuro-specific miR-29 deficiency exhibit increased levels of IRP2 and transferrin receptor, increased iron content, and oxidative stress.
  
  
  
  Our results demonstrate that age-dependent miR-29 upregulation is an adaptive mechanism that counteracts the expression of some aging-related phenotypes and its anti-aging activity is primarily exerted by regulating intracellular iron homeostasis limiting excessive iron-exposure in neurons.
authors.affiliation: Scuola Normale Superiore, Laboratory of Biology (Bio@SNS), c/o Istituto di Biofisica del CNR, via 17 Moruzzi 1, 56124, Pisa, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Ripa
authors.affiliation: Scuola Normale Superiore, Laboratory of Biology (Bio@SNS), c/o Istituto di Biofisica del CNR, via 17 Moruzzi 1, 56124, Pisa, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Dolfi
authors.affiliation: Scuola Normale Superiore, Laboratory of Biology (Bio@SNS), c/o Istituto di Biofisica del CNR, via 17 Moruzzi 1, 56124, Pisa, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Terrigno
authors.affiliation: Wellcome Trust/Cancer Research UK Gurdon Institute, Tennis Court Road, Cambridge, CB2 1QN, UK.
authors.forename: Luca
authors.initials: L
authors.lastname: Pandolfini
authors.affiliation: Babraham Research Campus, CB22 3AT, Cambridge, UK.
authors.forename: Aurora
authors.initials: A
authors.lastname: Savino
authors.affiliation: Scuola Normale Superiore, Laboratory of Biology (Bio@SNS), c/o Istituto di Biofisica del CNR, via 17 Moruzzi 1, 56124, Pisa, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Arcucci
authors.affiliation: Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Beutenbergstr. 11, 07745, Jena, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Groth
authors.affiliation: Scuola Normale Superiore, Laboratory of Biology (Bio@SNS), c/o Istituto di Biofisica del CNR, via 17 Moruzzi 1, 56124, Pisa, Italy.
authors.forename: Eva
authors.initials: E
authors.lastname: Terzibasi Tozzini
authors.affiliation: Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Beutenbergstr. 11, 07745, Jena, Germany.
authors.forename: Mario
authors.initials: M
authors.lastname: Baumgart
authors.affiliation: Scuola Normale Superiore, Laboratory of Biology (Bio@SNS), c/o Istituto di Biofisica del CNR, via 17 Moruzzi 1, 56124, Pisa, Italy. alessandro.cellerino@sns.it.|Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Beutenbergstr. 11, 07745, Jena, Germany. alessandro.cellerino@sns.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cellerino
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D006706:Homeostasis / Q000235:genetics; D007501:Iron / Q000378:metabolism*; D019190:Iron Overload / Q000235:genetics / Q000378:metabolism; D035942:Iron Regulatory Protein 2 / Q000235:genetics / Q000378:metabolism; D007695:Killifishes / Q000235:genetics* / Q000254:growth & development*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics; D015027:Zebrafish / Q000235:genetics
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger; D007501:Iron; D035942:Iron Regulatory Protein 2