title: miR-96, miR-145 and miR-9 expression increases, and IGF-1R and FOXO1 expression decreases in peripheral blood mononuclear cells of aging humans.
abstract: In mammals, the IGF-1 pathway affects the phenotype of aging. Since the function of the immune system is modulated by IGF-1, it is plausible that immunosenescence might in part result from altered control by this pathway. We therefore examined whether the expression of IGF-1R, FOXO1, and FOXO3a in peripheral blood mononuclear cells (PBMC) changes with age and if this might be due to changes in the expression of select miRNAs.
  
  
  
  The expression of IGF-1R, FOXO1, FOXO3a, as well as of miR-9, miR-96, miR-99a, miR-132, miR-145, and miR-182 was examined in PBMC of young (27.8 ± 3.7 years), elderly (65.6 ± 3.4 years), and long-lived (94.0 ± 3.7 years) Polish Caucasians using real-time PCR. mRNA/miRNA interactions were studied in HEK 293 cells using luciferase-expressing pmirGLO reporter vector.
  
  
  
  The median expression of IGF-1R decreased with age (p < 0.000001), as did the expression of FOXO1 (p < 0.000001), while the expression of FOXO3a remained stable. We also found an age-associated increase of the median expression of miR-96 (p = 0.002), miR-145 (p = 0.024) and miR-9 (p = 0.026), decrease of the expression of miR-99a (p = 0.037), and no changes regarding miR-132 and miR-182. Functional studies revealed that miR-96 and miR-182 interacted with human IGF-1R mRNA, and that miR-145 and miR-132 interacted with human FOXO1 mRNA.
  
  
  
  The age-associated higher expression of miR-96 and miR-145 might contribute to the lower expression of IGF-1R while the higher expression of miR-96, miR-145 and miR-9 might contribute to the lower expression of FOXO1 in peripheral blood mononuclear cells of aging humans. Sustained expression/function of FOXO3a but not of the other two genes might be important for the maintenance of the immune system function in these individuals.
authors.affiliation: Department of Geriatrics and Gerontology, Medical Centre of Postgraduate Education, Marymoncka 99/103, 01-813, Warsaw, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Budzinska
authors.affiliation: Department of Geriatrics and Gerontology, Medical Centre of Postgraduate Education, Marymoncka 99/103, 01-813, Warsaw, Poland.|Department of Human Epigenetics, Mossakowski Medical Research Centre, PAS, Pawinskiego 5, 02-106, Warsaw, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Owczarz
authors.affiliation: Department of Geriatrics and Gerontology, Medical Centre of Postgraduate Education, Marymoncka 99/103, 01-813, Warsaw, Poland.|Department of Human Epigenetics, Mossakowski Medical Research Centre, PAS, Pawinskiego 5, 02-106, Warsaw, Poland.
authors.forename: Eliza
authors.initials: E
authors.lastname: Pawlik-Pachucka
authors.affiliation: Department of Geriatrics and Gerontology, Medical Centre of Postgraduate Education, Marymoncka 99/103, 01-813, Warsaw, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Roszkowska-Gancarz
authors.affiliation: PolSenior Project, International Institute of Molecular and Cell Biology, Trojdena 4, 02-109, Warsaw, Poland.
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Slusarczyk
authors.affiliation: Department of Geriatrics and Gerontology, Medical Centre of Postgraduate Education, Marymoncka 99/103, 01-813, Warsaw, Poland. mpuzianowska@imdik.pan.pl.|Department of Human Epigenetics, Mossakowski Medical Research Centre, PAS, Pawinskiego 5, 02-106, Warsaw, Poland. mpuzianowska@imdik.pan.pl.
authors.forename: Monika
authors.initials: M
authors.lastname: Puzianowska-Kuznicka
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics; D005260:Female; D000071161:Forkhead Box Protein O1 / Q000096:biosynthesis / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D057809:HEK293 Cells; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D017526:Receptor, IGF Type 1; D017451:Receptors, Somatomedin / Q000096:biosynthesis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; C000597236:IGF1R protein, human; C541010:MIRN145 microRNA, human; C541874:MIRN92 microRNA, human; C541492:MIRN96 microRNA, human; D035683:MicroRNAs; D017451:Receptors, Somatomedin; D004247:DNA; D017526:Receptor, IGF Type 1
keywords: Epigenetic drift; Forkhead box O1 transcription factor; Forkhead box O3a transcription factor; Insulin-like growth factor-1 receptor; Peripheral blood mononuclear cells; Successful aging; miRNA