47EFFECTS OF AGEING AND VITAMIN D DEFICIENCY ON VITAMIN D RECEPTOR (VDR) EXPRESSION IN HUMAN SKELETAL MUSCLE

Background and aim. Vitamin D exerts its biochemical function on skeletal muscle through vitamin D receptors (VDR). Vitamin D deficiency is highly prevalent in the general population especially in the elderly. It is postulated that lower vitamin D levels lead to reduced expression of VDR in skeletal muscles. This then may lead to reduced muscle strength, function and ultimately falls in the elderly. The aim of this study was to examine the relationship between human ageing, circulating vitamin D levels and VDR expression in human skeletal muscle. Methods. Twenty six participants were recruited to the study; 8 young participants, 8 older participants who were vitamin D sufficient (25-OH-D3 ≥50 nmol/L) and 10 older participants who were vitamin D insufficient (<50nmol/L). Blood samples were obtained for the determination of serum 25-OH-D3, calcium and parathyroid hormone (the latter only for older participants); and a muscle biopsy of their thigh (vastus lateralis muscle) was performed using a Magnum biopsy system. Real time quantitative PCR was used to measure the expression of VDR and some of its target genes (myostatin, Sir1, PPARα and PPARδ) in human skeletal muscle. VDR protein content was measured using Western Blotting. Main findings. Hypovitaminosis D was highly prevalent in the young participants recruited into the study, but it was not statistically different from the older participants who were vitamin D insufficient. Higher expression of VDR and PPARδ mRNA was observed in both older sufficient and insufficient groups when compared with the younger group (p=0.01). There was also higher sirt1 mRNA expression (p=0.00) and a tendency towards higher PPARα expression (p=0.07) in the older sufficient group when compared to the younger group. There was no difference in skeletal muscle content of the myostatin gene between groups. When the young group was compared with the older insufficient group, levels of VDR mRNA and PPARδ were still higher in the older group. Gene expression did not appear to be strongly influenced by circulating 25-OH-D3 levels in any of the respective participant groups. Western blotting was unsuccessful in detecting VDR protein content despite the use of 2 different VDR antibodies. Tissue availability and time constraints precluded further work to be done. Conclusion. Similar VDR mRNA and target gene expression levels were expressed in both older sufficient and insufficient groups; and higher VDR mRNA was seen in the older insufficient group compared with the younger participants. This suggests that the ageing process may be influencing the expression of these genes. Circulating 25-OH-D3 levels did not appear to affect gene expression.