Background: Level exercise leads to focal structural damage in muscle
fibers and to an increase of creatine kinase in the blood. We question
ed whether it also induces activation of young and adult muscle satell
ite cells toward proliferation. Methods: Rats of two different ages, 6
and 16 weeks, were forced to run on a level treadmill and killed at d
ifferent time intervals, The temporal profile, up to 3 weeks, of muscl
e damage was investigated by quantification of the focally disturbed f
iber area in longitudinal sections of the m. soleus. Bromodeoxyuridine
(BrdU) was injected before death to determine the labeling index of s
atellite cells, Labeled and unlabeled satellite cells, myonuclei, and
fibers were counted in cross sections of the belly part of the muscles
. Results: The muscle fiber damage differed in both amount and tempora
l profile between young and older animals, Damage was already visible
immediately after running. However, whereas in the younger animal the
amount of damage increased gradually in time until 8% at 48 hours and
disappeared to almost control levels at 1 week after running, in the o
lder animals the amount of damage was lower but remained present for a
t least 2 weeks. The cell kinetic data on both groups showed a prolife
ration response of satellite cells throughout the muscle. The effects
were most pronounced in the older rats. In these rats a large increase
of the labeling index was found between 24 hours and 1 week, whereas
the total number of satellite cells was consistently higher from 2 day
s on until 2 weeks after running. In the younger animals roughly the s
ame time pattern was observed. Conclusion: Since the damage differed i
n amount and time between the two age groups, we conclude that the qui
ck and huge proliferation response is due to leakage of mitogenic fact
ors through small membrane disruptions that are generated during the e
xercise itself. (C) 1995 Wiley-Liss, Inc.