Age-related differences in the expression of circulating microRNAs: miR-21 as a new circulating marker of inflammaging

• Published in: Mechanisms of ageing and development Vol. 133; no. 11-12; pp. 675 - 685
• Main Authors: Olivieri, Fabiola, Spazzafumo, Liana, Santini, Gabriele, Lazzarini, Raffaella, Albertini, Maria Cristina, Rippo, Maria Rita, Galeazzi, Roberta, Abbatecola, Angela Marie, Marcheselli, Fiorella, Monti, Daniela, Ostan, Rita, Cevenini, Elisa, Antonicelli, Roberto, Franceschi, Claudio, Procopio, Antonio Domenico
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 01.11.2012; Elsevier
• Subjects: Adult; Age Factors; Aged; Aged, 80 and over; Aging; Biological and medical sciences; Biomarkers - metabolism; C-Reactive Protein - biosynthesis; Cardiovascular Diseases - metabolism; Centenarians; Centenarians offspring; Circulating microRNA; Circulating miR-21; Cohort Studies; Development. Metamorphosis. Moult. Ageing; Fibrinogen - biosynthesis; Fundamental and applied biological sciences. Psychology; Humans; Inflammation; MicroRNAs - blood; MicroRNAs - metabolism; Middle Aged; Models, Statistical; Oligonucleotide Array Sequence Analysis; Protein-Serine-Threonine Kinases - metabolism; Receptors, Transforming Growth Factor beta - metabolism; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Centenarians; Circulating microRNA; Centenarians offspring; Circulating miR-21; Gene silencing; Vertebrata; Senescence; Mammalia; Micro RNA; Age
• ISSN: 0047-6374; 1872-6216; 1872-6216
• DOI: 10.1016/j.mad.2012.09.004

► Profiling of circulating miRs revealed age-related differences. ► MiR-21 was decreased in centenarians and increased in CVD patients. ► A significant correlation between miR-21 and C-reactive protein and fibrinogen was observed. ► MiR-21 appears as circulating biomarker of inflammation in aging process and CVD. 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 100years underwent miR plasma profiling. The validation cohort consisted of 111 healthy adults (CTR) aged 20–105years 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.