Altered cellular heterogeneity as a possible mechanism for the maintenance of organ function in senescent animals.

Abstract

We tested the hypothesis that an alteration in the functional heterogeneity of cell populations (i.e., changes occurring in sensitivity and responsiveness to external stimuli among individual cells) may be a mechanism by which some organs are able to resist age-related decrements in function. To this end, changes in cytoplasmic free calcium concentration ([Ca2+]i) following glucose stimulation of individual pancreatic beta cells isolated from male F344 rats of ages 6, 12, and 26 mo were used as a model for evaluating responsiveness and sensitivity. Changes in [Ca2+]i of individual beta cells were monitored using fura-2 microspectrofluorimetry. No differences were observed in [Ca2+]i or in insulin secretion per beta cell among the age groups at any of the glucose concentrations. However, the percentage of beta cells that were responsive to a stimulatory glucose concentration (> 5.5 mM) was significantly greater in islets from the 26-mo-old rats (76%) as compared to the 6- and 12-mo-old animals (63% and 65%, respectively). Of the responsive beta cells, a significantly greater percentage of those from the 26-mo-old rats (72%) responded at the lowest stimulatory glucose concentration (7.5 mM) as compared to the 6- and 12-mo-old animals (58% and 60%, respectively). These data suggest that the maintenance of organ function in older rats at a level comparable to that of younger animals may be accomplished, in part, by an increase in the percentage of cells that are responsive to stimuli and/or by an increase in the sensitivity of the responsive cells.