Journals of Gerontology Series A: Biological Sciences and Medical Sciences, Vol 52, Issue 1 B53-B58, Copyright © 1997 by The Gerontological Society of America
Altered cellular heterogeneity as a possible mechanism for the maintenance of organ function in senescent animals
RC Ruhe, DL Curry and RB McDonald
Department of Nutrition, University of California, Davis, USA.
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.
