title: Age-related differences in the expression of circulating microRNAs: miR-21 as a new circulating marker of inflammaging.
abstract: Circulating microRNAs (miRs) have been investigated as diagnostic/prognostic biomarkers in human diseases. However, little is known about their expression throughout the aging process. Eleven healthy individuals aged 20, 80 and 100 years underwent miR plasma profiling. The validation cohort consisted of 111 healthy adults (CTR) aged 20-105 years and included 30 centenarians. In addition, 34 patients with cardiovascular disease (CVD) and 15 healthy centenarian offspring (CO) were enrolled. An exploratory factorial analysis grouped the miRs into three main factors: factor 1 primarily higher in 20-year-old subjects, but these differences did not reach statistical significance, factor 2 primarily higher in octogenarians and factor 3 primarily higher in centenarians. MiR-21, the most highly expressed miR of factors 2 and 3, was further validated, confirming the differences in the age groups. MiR-21 expression was higher in the CVD patients and lower in the CO compared to the age-matched CTR. MiR-21 was correlated with C-reactive protein and fibrinogen levels. TGF-β signaling was the predicted common pathway targeted by miRs of factors 2 and 3. TGF-βR2 mRNA, a validated miR-21 target, showed the highest expression in the leukocytes from a subset of the octogenarians. Our findings suggest that miR-21 may be a new biomarker of inflammation.
authors.affiliation: Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona, Italy. f.olivieri@univpm.it
authors.forename: Fabiola
authors.initials: F
authors.lastname: Olivieri
authors.forename: Liana
authors.initials: L
authors.lastname: Spazzafumo
authors.forename: Gabriele
authors.initials: G
authors.lastname: Santini
authors.forename: Raffaella
authors.initials: R
authors.lastname: Lazzarini
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Albertini
authors.forename: Maria Rita
authors.initials: MR
authors.lastname: Rippo
authors.forename: Roberta
authors.initials: R
authors.lastname: Galeazzi
authors.forename: Angela Marie
authors.initials: AM
authors.lastname: Abbatecola
authors.forename: Fiorella
authors.initials: F
authors.lastname: Marcheselli
authors.forename: Daniela
authors.initials: D
authors.lastname: Monti
authors.forename: Rita
authors.initials: R
authors.lastname: Ostan
authors.forename: Elisa
authors.initials: E
authors.lastname: Cevenini
authors.forename: Roberto
authors.initials: R
authors.lastname: Antonicelli
authors.forename: Claudio
authors.initials: C
authors.lastname: Franceschi
authors.forename: Antonio Domenico
authors.initials: AD
authors.lastname: Procopio
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000096:biosynthesis; D002318:Cardiovascular Diseases / Q000378:metabolism; D015331:Cohort Studies; D005340:Fibrinogen / Q000096:biosynthesis; D006801:Humans; D007249:Inflammation; D035683:MicroRNAs / Q000097:blood* / Q000378:metabolism; D008875:Middle Aged; D015233:Models, Statistical; D020411:Oligonucleotide Array Sequence Analysis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D015415:Biomarkers; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D018125:Receptors, Transforming Growth Factor beta; D005340:Fibrinogen; D002097:C-Reactive Protein; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II