Cellular mechanisms of the age-related decrease in renal phosphate reabsorption

Abstract

The aging process in humans and in the rat is associated with an impairment in renal tubular reabsorption of Pi and renal tubular adaptation to a low Pi diet. The purposes of the present study were to determine whether changes in the abundance of type II Na-Pi cotransporter (NaPi-2) protein and/or mRNA play a role in the age-related decrease in Na-Pi cotransport activity, and to further determine the cellular mechanisms of impaired adaptation to a low Pi diet. In studies performed in 3- to 4-month-old young adult rats and 12- to 16-month-old aged rats we found that there was an age-related twofold decrease in proximal tubular apical brush border membrane (BBM) Na-Pi cotransport activity, which was associated with similar decreases in BBM NaPi-2 protein abundance and renal cortical NaPi-2 mRNA level. Immunohistochemistry showed lower NaPi-2 protein expression in the BBM of proximal tubules of superficial, midcortical, and juxtamedullary nephrons. We also found that in response to chronic (7 days) and/or acute (4 hr) feeding of a low Pi diet there were similar adaptive increases in BBM Na-Pi cotransport activity and BBM NaPi-2 protein abundance in both young and aged rats. However, BBM Na-Pi cotransport activity and BBM NaPi-2 protein abundance were still significantly lower in aged rats, in spite of a significantly lower serum Pi concentration in aged rats. The results indicate that impaired expression of the type II renal Na-Pi cotransporter protein at the level of the apical BBM plays an important role in the age-related impairment in renal tubular reabsorption of Pi and renal tubular adaptation to a low Pi diet.