title: Increased micro-RNA 29b in the aged brain correlates with the reduction of insulin-like growth factor-1 and fractalkine ligand.
abstract: Microglia develop an inflammatory phenotype during normal aging. The mechanism by which this occurs is not well understood, but might be related to impairments in several key immunoregulatory systems. Here we show that micro-RNA (miR)-29a and miR-29b, 2 immunoregulatory micro-RNAs, were increased in the brain of aged BALB/c mice compared with adults. Insulin-like growth factor-1 (IGF-1) and fractalkine ligand (CX3CL1) are negative modulators of microglial activation and were identified as targets of miR-29a and miR-29b using luciferase assay and primary microglia transfection. Indeed, higher expression of miR-29b in the brain of aged mice was associated with reduced messenger RNA (mRNA) levels of IGF-1 and CX3CL1. Parallel to these results in mice, miR-29a and miR-29b were also markedly increased in cortical brain tissue of older individuals (mean, 77 years) compared with middle-aged adults (mean, 45 years). Moreover, increased expression of miR-29b in human cortical tissue was negatively correlated with IGF-1 and CX3CL1 expression. Collectively, these data indicate that an age-associated increase in miR-29 corresponded with the reduction of 2 important regulators of microglia, IGF-1 and CX3CL1.
authors.affiliation: Department of Neuroscience, The Ohio State University, Columbus, OH, USA.
authors.forename: Ashley M
authors.initials: AM
authors.lastname: Fenn
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Smith
authors.forename: Amy E
authors.initials: AE
authors.lastname: Lovett-Racke
authors.forename: Mireia
authors.initials: M
authors.lastname: Guerau-de-Arellano
authors.forename: Caroline C
authors.initials: CC
authors.lastname: Whitacre
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Godbout
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D000073883:CX3C Chemokine Receptor 1; D002540:Cerebral Cortex / Q000378:metabolism*; D054428:Chemokine CX3CL1 / Q000378:metabolism*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D008024:Ligands; D008297:Male; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000378:metabolism*; D017628:Microglia / Q000378:metabolism*; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; D054428:Chemokine CX3CL1; D008024:Ligands; D035683:MicroRNAs; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D007334:Insulin-Like Growth Factor I
keywords: Aging; Fractalkine; Insulin-like growth factor; Microglia; Neuroinflammation; miR-29a; miR-29b