Ageing is associated with a progressive deterioration in the functions of many organs within the body. In tissue with high cell turnover, the maintenance of the stem cells is of particular importance. Any accumulation of damage in stem cells may affect their function and hence threaten the homeostasis and regenerative capacity of the tissue. The small intestine represents a good model for the study of stem cells because of its spatial and hierarchical organisation. We have examined the effect of age on stem cell regenerative capacity after irradiation, using the microcolony assay. Crypt survival levels, the growth rate of surviving crypts, and the number of cells able to repopulate a crypt have been investigated by irradiating groups of 6–7 month old and 28–30 month old ICRFa male mice. After high doses of irradiation, the surviving crypts in old mice were both smaller and fewer in number than in young mice. The growth rate of surviving crypts was determined by measuring the crypt area and the number of cells/crypt at various times after 14 Gy irradiation. There was a growth delay of between about one half and one day in the older mice. Surprisingly, the number of clonogenic cells per crypt was estimated to be greater in the older mice. These studies indicate important age-related alterations in the capacity to regenerate the crypts after radiation damage.

REFERENCES

Cai
W. B.
,
Roberts
S. A.
,
Bowley
E.
,
Hendry
J. H.
,
Potten
C. S.
(
1997
).
Differential survival of murine small and large intestinal crypts following ionizing radiation.
Int. J. Radiat. Biol
71
,
145
155
Cai
W. B.
,
Roberts
S. A.
,
Potten
C. S.
(
1997
).
The number of clonogenic cells in crypts in three regions of murine large intestine.
Int. J. Radiat. Biol
71
,
573
579
Davies
I.
,
Shofield
J. D.
(
1980
).
Connective tissue ageing: the influence of a lathyrogen (ss-aminopropionitrile) on the lifespan of female C57/ICRFa mice.
Exp. Gerontol
15
,
487
494
Deshner
E. E.
,
Godbold
J.
,
Lynch
H. T.
(
1988
).
Rectal epithelial cell proliferation in a group of young adults. Influence of age and genetic risk for colon cancer.
Cancer
61
,
2286
2290
Ellsworth
J. L.
,
Schimke
R. T.
(
1990
).
On the frequency of metaphase chromosome aberrations in the small intestine of aged rats.
J. Gerontol
45
,
94
100
Fry
R. J. M.
,
Lesher
S.
,
Kohn
H. I.
(
1961
).
Age effect on cell transit time in mouse jejunal epithelium.
Am. J. Physiol
201
,
213
216
Fry
R. J. M.
,
Lesher
S.
,
Kohn
H. I.
(
1962
).
Influence of age on the transit time of cells of the mouse intestinal epithelium. III Ileum.
Lab. Invest
11
,
289
293
Hendry
J. H.
,
Roberts
S. A.
,
Potten
C. S.
(
1992
).
The clonogen content of murine intestinal crypts: Dependence on radiation dose used in its determination.
Radiation Res
132
,
115
119
Holt
P. R.
,
Yeh
K.
,
Kotler
D. P.
(
1988
).
Altered control of proliferation in proximal small intestine.
Proc. Nat. Acad. Sci. USA
85
,
2771
2775
Kirkwood
T. B. L.
,
Franceschi
C.
(
1992
).
Is ageing as complex as it would appear?.
Ann. NY Acad. Sci
663
,
412
417
Lesher
S.
,
Fry
R. J. M.
,
Kohn
H. I.
(
1961
).
Age and the generation time of the mouse duodenal epithelial cell.
Exp. Cell Res
24
,
334
343
Martin
K.
,
Kirkwood
T. B. L.
,
Potten
C. S.
(
1998
).
Ages changes in stem cells of murine small intestinal crypts.
Exp. Cell Res
241
,
316
323
Merritt
A. J.
,
Potten
C. S.
,
Kemp
C. J.
,
Hickman
J. A.
,
Balmain
A.
,
Lane
D. P.
,
Hall
P. A.
(
1994
).
The role of p53 in spontaneous and radiation induced apoptosis in the gastrointestinal tract of normal and p53-deficient mice.
Cancer Res
54
,
614
617
Paganelli
G. M.
,
Santucci
R.
,
Biasco
,
Miglioli
M.
,
Barbara
L.
(
1990
).
Effect of sex and age on rectal cell renewal in humans.
Cancer Lett
53
,
117
121
Potten
C. S.
,
Rezvani
M.
,
Hendry
J. H.
,
Moore
J. V.
,
Major
D.
(
1981
).
The correction of intestinal microcolony counts for variation in size.
Int. J. Rad. Biol
40
,
321
326
Potten
C. S.
,
Hendry
J. H.
,
Moore
J. V.
(
1987
).
Estimates of the number of clonogenic cells in crypts of murine small intestine.
Virchows Arch. B Cell Pathol
53
,
227
234
Potten
C. S.
,
Loeffler
M.
(
1990
).
Stem cells: attributes, cycles, spirals, pitfalls and uncertainties. Lessons for and from the crypt.
Development
110
,
1001
1020
Potten
C. S.
(
1992
).
The significance of spontaneous and induced apoptosis in the gastrointestinal tract of mice.
Cancer and Metastasis Reviews
11
,
179
195
Potten
C. S.
,
Booth
C.
,
Pritchard
D. M.
(
1997
).
The intestinal epithelial stem cell: the mucosal governor.
Int. J. Exp. Pathol
78
,
219
243
Roberts
S. A.
(
1990
).
DRFIT: A program for fitting radiation survival models.
Int. J. Rad. Biol
57
,
1243
1246
Roberts
S. A.
,
Potten
C. S.
(
1994
).
Clonogen content of intestinal crypts: its deduction using a microcolony assay on whole mount preparations and its dependence on radiation dose.
Int. J. Rad. Biol
65
,
477
481
Roberts
S. A.
,
Hendry
J. H.
,
Potten
C. S.
(
1995
).
Deduction of the clonogen content of intestinal crypts: a direct comparison of two-dose and multiple-dose methodologies.
Radiation Res
141
,
303
308
Roncucci
L.
,
Ponz de Leon
M.
,
Scalmati
A.
,
Malagoli
G.
,
Pratissoli
S.
,
Perini
M.
,
Chahin
N. J.
(
1988
).
The influence of age on colonic epithelial cell proliferation.
Cancer
62
,
2373
2377
Withers
H. R.
,
Elkind
M. M.
(
1970
).
Microcolony survival assay for cells of mouse intestinal mucosa exposed to radiation.
Int. J. Radiat. Biol
17
,
261
268
This content is only available via PDF.