Influence of age and physical fitness on miRNA-21, TGF-β and its receptors in leukocytes of healthy women

Abstract

Rationale: The TGF-beta superfamily has been shown to play an important;vie 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-beta 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-beta or its receptors. Methods: 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-beta levels were determined together with the mRNA expression of TGF-beta, TGF-beta R1, TGF-beta RII, and miRNA-21 (known to interfere with TGF-beta signalling) in PBMCs. Results: 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 OR: 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-beta and TGF-beta mRNA levels from PBMCs did not differ between young and old women whereas, both TGF-beta R1/GAPDH (YF: 4.07 (1.38-14.60); OF: 2.08 (0.14-28.81); p=0.020) and TGF-beta RII/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-beta R1 expression correlated negatively with miRNA-21 expression in PBMCs (1)=-0.315; p=0.004,). Interestingly, hs-CRP and miRNA correlated positively with handgrip strength (P=0.237 and p=243, p<0.05), while none of the TGF-beta-related parameters were related to physical performance. Conclusion: The results suggest that age affects TGF-beta signalling in leukocytes by altering the expression levels of its receptors. These changes seem to occur independently of physical fitness of old women.