title: Influence of age and physical fitness on miRNA-21, TGF-β and its receptors in leukocytes of healthy women.
abstract: The TGF-β superfamily has been shown to play an important role in a wide range of physiological as well as pathological processes including ageing, immune modulation, atherosclerosis and cancer development. The aim of the current study was to investigate (i) whether TGF-β signalling in peripheral blood mononuclear cells (PBMCs) would differ between young and old females and (ii) whether physical performance parameters of elderly women would be related to the expression of TGF-β or its receptors. Sixteen healthy young (22-28 years; YF) and 90 healthy older (65-92 years; OF) females participated in the study. In addition to several components of health-related physical fitness, circulating CRP and TGF-β levels were determined together with the mRNA expression of TGF-β, TGF-βRI, TGF-βRII, and miRNA-21 (known to interfere with TGF-β signalling) in PBMCs. Physical fitness as determined by 6-minutes walking test (YF:median 932 (range 573-1254) m; OF:360 (114-558) m), handgrip strength (YF: 32 (24-39) kg; OF:18(10-30) kg), relative isokinetic peak torque of knee extensors (YF:1.9 (1.2- 2.3) Nm/kg; OF:1.0 (0.2-1.9) Nm/kg and flexors (YF: 1.1 (0.7- 1.5) Nm/kg; OF: 0.5 (0.2-1.0) Nm/kg was substantially lower in older women (p<0.001 for all comparisons). These changes were paralleled by an increase in hs-CRP (YF: 0.9 (0.1-4.3)mg/L; OF: 2.3 (0.3-56.7)mg/L,p<0.001). Serum levels of TGF-β and TGF-β mRNA levels from PBMCs did not differ between young and old women whereas, both TGF- βRI/GAPDH (YF: 4.07 (1.38-14.60); OF: 2.08 (0.14-28.81); p=0.020) and TGF-βRII/GAPDH levels (YF: 3.16 (1.14- 10.25); OF: 1.71 (0.51-14.86); p=0.020) were lower with respect to old age. In elderly women, only TGF-βRΙ expression correlated negatively with miRNA-21 expression in PBMCs (ρ=-0.315; p=0.004). Interestingly, hs-CRP and miRNA correlated positively with handgrip strength (ρ=0.237 and ρ=243, p<0.05), while none of the TGF-β-related parameters were related to physical performance. The results suggest that age affects TGF-β signalling in leukocytes by altering the expression levels of its receptors. These changes seem to occur independently of physical fitness of old women.
authors.affiliation: University of Vienna, Research Platform Active Ageing, Althanstraße 14, 1090 Vienna, Austria.
authors.forename: Barbara
authors.initials: B
authors.lastname: Halper
authors.affiliation: University of Vienna, Centre for Sport Science and University Sports, Department of Sport and Exercise Physiology, Auf der Schmelz 6, 1150 Vienna, Austria.
authors.forename: Marlene
authors.initials: M
authors.lastname: Hofmann
authors.affiliation: University of Vienna, Research Platform Active Ageing, Althanstraße 14, 1090 Vienna, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Oesen
authors.affiliation: University of Vienna, Research Platform Active Ageing, Althanstraße 14, 1090 Vienna, Austria.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Franzke
authors.affiliation: University of Vienna, Centre for Sport Science and University Sports, Department of Preventive and Rehabilitative Training Science, Auf der Schmelz 6, 1150 Vienna, Austria.
authors.forename: Petra
authors.initials: P
authors.lastname: Stuparits
authors.affiliation: Study Lab G.m.b.H., Davidgasse 87-89, 1100 Vienna.
authors.forename: Claudia
authors.initials: C
authors.lastname: Vidotto
authors.affiliation: University of Vienna, Centre for Sport Science and University Sports, Department of Sport and Exercise Physiology, Auf der Schmelz 6, 1150 Vienna, Austria.
authors.forename: Harald
authors.initials: H
authors.lastname: Tschan
authors.affiliation: University of Vienna, Centre for Sport Science and University Sports, Department of Sport and Exercise Physiology, Auf der Schmelz 6, 1150 Vienna, Austria.
authors.forename: Norbert
authors.initials: N
authors.lastname: Bachl
authors.affiliation: Karl Landsteiner Institute for Remobilization and Functional Health/ Institute for Physical Medicine and Rehabilitation, Kaiser Franz Joseph Hospital, Social Medical Centre South, Kundratstrasse 3, 1100 Vienna, Austria.
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Strasser
authors.affiliation: Karl Landsteiner Institute for Remobilization and Functional Health/ Institute for Physical Medicine and Rehabilitation, Kaiser Franz Joseph Hospital, Social Medical Centre South, Kundratstrasse 3, 1100 Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Quittan
authors.affiliation: University of Vienna, Research Platform Active Ageing, Althanstraße 14, 1090 Vienna, Austria.|University of Vienna, Faculty of Life Sciences, Department of Nutritional Science, Althanstraße 14, 1090 Vienna, Austria.
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Wagner
authors.affiliation: University of Vienna, Research Platform Active Ageing, Althanstraße 14, 1090 Vienna, Austria.|University of Vienna, Centre for Sport Science and University Sports, Department of Sport and Exercise Physiology, Auf der Schmelz 6, 1150 Vienna, Austria.
authors.forename: Barbara
authors.initials: B
authors.lastname: Wessner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood / Q000276:immunology / Q000502:physiology*; D001823:Body Composition; D002097:C-Reactive Protein / Q000032:analysis; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D064368:Healthy Volunteers; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D035683:MicroRNAs / Q000097:blood*; D010807:Physical Endurance / Q000502:physiology; D010809:Physical Fitness / Q000502:physiology*; D012333:RNA, Messenger / Q000097:blood; D016059:Range of Motion, Articular; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D016138:Walking; D055815:Young Adult
chemical_list: C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D002097:C-Reactive Protein
keywords: Inflamm-ageing; TGF-β Pathway; TGF-β receptors; Vienna Active Ageing Study.; microRNA-21; physical performance