ALTERED CELLULAR HETEROGENEITY AS A POSSIBLE MECHANISM FOR THE MAINTENANCE OF ORGAN FUNCTION IN SENESCENT ANIMALS

We tested the hypothesis that an alternation in the functional heterog eneity of cell populations (i.e., changes occurring in sensitivity and responsiveness to external stimuli among individual cells) may be a m echanism by which some organs are able to resist age-related decrement s in function. To this end, changes in cytoplasmic free calcium concen tration ([Ca2+](i)) following glucose stimulation of individual pancre atic beta cells isolated from male F344 rats of ages 6, 12, and 26 mo were used as a model for evaluating responsiveness and sensitivity. Ch anges in [Ca2+](i) of individual beta cells were monitored using fura- 2 microspectrofluorimetry. No differences were observed in [Ca2+](i) o r in insulin secretion per beta cell among the age groups at any of th e glucose concentrations. However, the percentage of beta cells that w ere responsive to a stimulatory glucose concentration (>5.5 mM) was si gnificantly greater in islets from the 26-mo-old rats (76%) as compare d to the 6- and 12-mo-old animals (63% and 65%, respectively). Of the responsive beta cells, a significantly greater percentage of those fro m 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 (5 8% 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.