Rc. Ruhe et al., ALTERED CELLULAR HETEROGENEITY AS A POSSIBLE MECHANISM FOR THE MAINTENANCE OF ORGAN FUNCTION IN SENESCENT ANIMALS, The journals of gerontology. Series A, Biological sciences and medical sciences, 52(1), 1997, pp. 53-58
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.