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

The TGF-ß 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-ß 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-ß 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-ß levels were determined together with the mRNA expression of TGF-ß, TGF-ßRI, TGF-ßRII, and miRNA-21 (known to interfere with TGF-ß 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-ß and TGF-ß mRNA levels from PBMCs did not differ between young and old women whereas, both TGF- ßRI/GAPDH (YF: 4.07 (1.38-14.60); OF: 2.08 (0.14-28.81); p=0.020) and TGF-ßRII/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-ßRΙ 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-ß-related parameters were related to physical performance. The results suggest that age affects TGF-ß signalling in leukocytes by altering the expression levels of its receptors. These changes seem to occur independently of physical fitness of old women.

Serum concentrations of insulin-like growth factor-1, members of the TGF-beta superfamily and follistatin do not reflect different stages of dynapenia and sarcopenia in elderly women.

There is a high need for blood-based biomarkers detecting age-related changes in muscular performance at an early stage. Therefore, we investigated whether serum levels of growth and differentiation factor-15 (GDF-15), activin A, myostatin, follistatin, and insulin-like growth factor-1 (IGF-1) would reflect age- and physical performance-related differences between young (22-28 years) and elderly (65-92 years) females. Isokinetic peak torque of knee extension (PTE) was measured in young females to obtain reference values for the discrimination of different stages of age-associated muscle weakness. Additionally, elderly women were screened for sarcopenia using the algorithm of the European Working Group on Sarcopenia in Older People (low muscle mass in addition to low PTE and/or low walking speed). IGF-1 levels were higher and GDF-15 levels were lower in young females in comparison to the elderly (p < 0.01), whereas members of the activin A/myostatin/follistatin axis showed similar levels across age groups. In older women, IGF-1 correlated negatively with age (ρ = -0.359, p < 0.01) and positively with muscle mass (ρ = 0.365, p < 0.01). In contrast, GDF-15 correlated positively with age (ρ = 0.388, p < 0.001) and negatively with muscle mass (ρ = -0.320, p < 0.01). However, none of the serum markers differed between women classified as non-, mildly and severely dynapenic/sarcopenic. Multiple linear regression analyses revealed that a combination of all blood-based biomarkers obtained in addition to age and fat mass moderately predicted muscle mass (+2.9%). Neither a single nor a combined set of tested biomarkers reflected the presence of dynapenia or sarcopenia in elderly women. However, due to the associations of IGF-1 and GDF-15 with correlates of muscle mass and function, these parameters remain promising candidates in a potential set of blood-based biomarkers to diagnose sarcopenia and/or dynapenia.