Expression of calbindin-D decreases with age in intestine and kidney

The calbindins are Ca-binding proteins whose expression is regulated by 1,25-dihydroxyvitamin D3, the active metabolite of vitamin D3. The calbindins are found in high amounts in the proximal intestine (calbindin-D-9k) and the kidney (calbindin-D-28k), and they are thought to play a role in Ca transport by these tissues. Ca absorption by the intestine and perhaps the kidney declines with age, and this could be due to decreased expression of calbindin. Therefore, the expression of calbindins-D-9k and -D-28k was measured in F344 rats aged 2, 6, 13, and 24 months. mRNA levels were measured by dot blot hybridization to synthetic cDNA oligonucleotide probes, and protein levels were measured by enzyme-linked immunosorbent assay using specific antisera. Intestinal calbindin-D-9k mRNA decreased markedly between 2 and 6 months of age, but it then increased significantly between 13 and 24 months. Calbindin-D-9k protein paralleled the decrease in mRNA between 2 and 6 months, but continued to decline at 13 and 24 months despite the rise in mRNA. In the kidney, calbindin-D-28k mRNA declined between 2 and 13 months and then plateaued. Calbindin-D-28k protein followed a similar pattern. In the same studies expression of calmodulin by the intestine and kidney did not change with age. Plasma 1,25-dihydroxyvitamin-D3 correlated well with the expression of calbindin-D-9k in the intestine at 2 and 6 months of age and with the expression of calbindin-D-28k in the kidney at all ages. Decreased expression of calbindin-D with age may contribute to the age-related decrease in Ca transport in intestine and kidney.