title: Immunosenescence-associated microRNAs in age and heart failure.
abstract: OBJECTIVE
  Ageing of the immune system, immunosenescence, is characterized by impaired lymphopoiesis, especially B-lymphocyte maturation, and is a hallmark of chronic heart failure (CHF). MicroRNAs (miRNAs) are non-coding, small RNAs, which post-transcriptionally control gene expression of multiple target genes. The miR-181 family is known to control haematopoietic lineage differentiation. Here, we study the role of the miR-181 family in immunosenescence and CHF.
  
  
  RESULTS
  We conducted a clinical study analysing peripheral blood (PB) for miRNA expression and leucocyte distribution of young healthy controls (25 ± 4 years; n = 30), aged healthy controls (64 ± 5 years; n = 13), and age-matched CHF patients (64 ± 11years; n = 18). The expression of miR-181 family members was reduced, whereas miR-34a was increased in PB of aged individuals. In particular, miR-181c was further reduced in age-matched CHF patients. In PB, we observed reduced numbers of lymphocytes, in particular cytotoxic T cells and B cells, with rising age, and the expression of miR-181 correlated with the number of B cells. Notably, in CHF patients, ischaemic heart failure was associated with a further reduction of total B cells as well as their subpopulations, such as memory B cells, compared with age-matched healthy volunteers.
  
  
  CONCLUSIONS
  Ageing- and CHF-associated changes in PB leucocyte subsets are paralleled by alterations in the expression of miRNAs involved in lymphopoiesis, which might play an important role in the age-related and CHF-mediated dysregulation of immune functions resulting in immunosenescence. Furthermore, miR-181c may serve as a marker for reduced immune functions in CHF patients.
authors.affiliation: Institute for Cardiovascular Regeneration, Center of Molecular Medicine, Theodor Stern Kai 7, D-60590 Frankfurt, Germany.
authors.forename: Timon
authors.initials: T
authors.lastname: Seeger
authors.forename: Fatima
authors.initials: F
authors.lastname: Haffez
authors.forename: Ariane
authors.initials: A
authors.lastname: Fischer
authors.forename: Ulrike
authors.initials: U
authors.lastname: Koehl
authors.forename: David M
authors.initials: DM
authors.lastname: Leistner
authors.forename: Florian H
authors.initials: FH
authors.lastname: Seeger
authors.forename: Reinier A
authors.initials: RA
authors.lastname: Boon
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Zeiher
authors.forename: Stefanie
authors.initials: S
authors.lastname: Dimmeler
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology*; D001402:B-Lymphocytes / Q000473:pathology; D016022:Case-Control Studies; D002908:Chronic Disease; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000502:physiology*; D006333:Heart Failure / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007107:Immune System / Q000502:physiology; D038041:Lymphopoiesis / Q000276:immunology*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000473:pathology; D055815:Young Adult
chemical_list: C540193:MIrn181 microRNA, human; D035683:MicroRNAs