Novel role of caveolin-1
for muscle function in aging and exercise
Sang
Aging and Apoptosis
Research Center, Seoul National University Institute on Aging, 28 Yongon Dong, ChongNo
Ku, Seoul 110-799, S.Korea
We have reported that caveolin-1
increases with aging in most of tissues of aged animals as well as senescent
cells and that this molecule would be responsible for age dependent
hypo-responsiveness to many agonists including growth factors. And we have
shown that the senescent phenotype of reduced mitogenic responses and
morphological alteration could be modulated by simple adjustment of caveolin-1
status. However, we have discovered that caeolin-1 is increasing with muscle differentiation,
while its level is decreased in the aged muscle tissue. Therefore, we paid a
special attention on the role of caveolin-1 in muscle tissues. Thereby, we
could observe the exercise-dependent induction of caveolin-1 with improvement
of insulin sensitivity. Moreover, we have succeeded in developing the new type
II diabetes animal model, which showed the apparent diabetic phenotype only at
age of 30 weeks without any evidence of obesity, but only in male mice in a
gender specific pattern. This reduced insulin sensitivity of the muscle tissue is
deeply related with changes in caveolin-1 status, its lowered caveolin-1 level
at the diabetic period. Therefore, we assumed that insulin sensitivity of the
muscle tissue would be dependent on caveolin-1 status. Restoration of
caveolin-1 status in muscle tissue with caveolin-1 gene injection could resume
the insulin sensitivity. Taken
together, these data strongly suggest that caveolin-1 would be important not
only in insulin sensitivity but also for differentiation of the muscle tissue. Therefore,
the adjustment of caveolin-1 status in muscle tissue would be a novel target
for control of Diabetes especially of non-obese type II diabetes and also for
induction of muscle differentiation.
Key words: caveolin, aging, exercise,
muscle