PUBLICATION
MicroRNA miR-29 controls a compensatory response to limit neuronal iron accumulation during adult life and aging
- Authors
- Ripa, R., Dolfi, L., Terrigno, M., Pandolfini, L., Savino, A., Arcucci, V., Groth, M., Terzibasi Tozzini, E., Baumgart, M., Cellerino, A.
- ID
- ZDB-PUB-171017-16
- Date
- 2017
- Source
- BMC Biology 15: 9 (Journal)
- Registered Authors
- Cellerino, Alessandro
- Keywords
- none
- MeSH Terms
-
- Aging/genetics*
- Animals
- Base Sequence
- Brain/metabolism
- Homeostasis/genetics
- Iron/metabolism*
- Iron Overload/genetics
- Iron Overload/metabolism
- Iron Regulatory Protein 2/genetics
- Iron Regulatory Protein 2/metabolism
- Killifishes/genetics*
- Killifishes/growth & development*
- MicroRNAs/genetics
- MicroRNAs/metabolism*
- Models, Biological
- Neurons/metabolism*
- RNA, Messenger/genetics
- RNA, Messenger/metabolism
- Up-Regulation/genetics
- Zebrafish/genetics
- PubMed
- 28193224 Full text @ BMC Biol.
Citation
Ripa, R., Dolfi, L., Terrigno, M., Pandolfini, L., Savino, A., Arcucci, V., Groth, M., Terzibasi Tozzini, E., Baumgart, M., Cellerino, A. (2017) MicroRNA miR-29 controls a compensatory response to limit neuronal iron accumulation during adult life and aging. BMC Biology. 15:9.
Abstract
Background 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.
Results 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.
Conclusions 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping