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MicroRNA miR-29 controls a compensatory response to limit neuronal iron accumulation during adult life and aging.

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.

SUBMITTER: Ripa R

PROVIDER: S-EPMC5304403 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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MicroRNA miR-29 controls a compensatory response to limit neuronal iron accumulation during adult life and aging.

Ripa Roberto R Dolfi Luca L Terrigno Marco M Pandolfini Luca L Savino Aurora A Arcucci Valeria V Groth Marco M Terzibasi Tozzini Eva E Baumgart Mario M Cellerino Alessandro A

BMC biology 20170213 1

<h4>Background</h4>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.<h4>Results</h4>Here, we show that microRNA-29 (miR-29) is induced during aging in ...[more]

PMID: 28193224

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MicroRNA miR-29 controls a compensatory response to limit neuronal iron accumulation during adult life and aging.

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MicroRNA miR-29 controls a compensatory response to limit neuronal iron accumulation during adult life and aging.

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