Age-related loss of nongoblet crypt cells parallels decreased secretion in rabbit descending colon

The effects of aging on active electrolyte transport and epithelial cell morphology were studied in rabbit descending colon. The rate of electrolyte transport was determined using the voltage-clamp technique, while computerized morphometric techniques were used to describe age-related and secretion-induced changes in histology. Comparison of percent water content of fecal pellets between young (2-3 mo) and mature (3.5-5 yr) animals demonstrated that mature animals had significantly decreased percent stool water. In mature animals, the total number of crypt epithelial cells was significantly less than in young animals, primarily due to the loss of crypt nongoblet cells. Crypt goblet cell number and area were not significantly changed from young to mature, while the crypt nongoblet cell number and area declined 38 and 28%, respectively, in the mature colon. Theophylline elicited dilatation of the crypt lumen. The decreased crypt nongoblet cell area correlated with a decreased theophylline-induced Cl- secretory response observed in the mature colon as measured by the change in short-circuit current (Isc). Also, a significant decrease in theophylline-stimulated active Cl- secretion was observed in mature vs. young animals in the presence of mucosal barium (5 mM) to eliminate active K+ secretion. The maximum theophylline plus barium-induced increase in Isc in young colon was 3.4 +/- 0.3 mueq.cm-2.h-1 and in mature colon 2.5 +/- 0.3 mueq.cm-2.h-1 (P less than 0.05). No significant difference in basal Isc and amiloride-inhibitable Na+ absorption was found between young and mature animals. The decreased capacity to secrete Cl- and the decrease in number and area of crypt nongoblet cells corresponds with the decrease in percent water content of mature fecal pellets.