Mitochondrial muscle health and muscle function in elderly

Sedentary aging is associated with the decline of mitochondrial and skeletal
muscle volume, quality and function. The causal link between the loss of
mitochondriale homeostasis and muscle health is unknown, however, both appear
with advancing age and are associated with the loss of functional capacity
corresponding increases in comorbidities and annual healthcare costs. We test
the hypothesis that a compromised muscle function in sedentary elderly is due
to an impaired mitochondrial health.

The present study aims to characterize the relation between skeletal muscle
mitochondrial metabolism and muscle health in physically compromised humans.

A detailed characterization of mitochondrial metabolism and muscle function
will be performed in well-defined, (compromised) elderly humans 65-80 years, in
a cross-sectional design. To obtain insight in causal relationships, we will
not only compare subjects that differ in mitochondrial function (physical
activity) but also select for subjects with high versus low muscle function.
Healthy, young (20-30 years,) individuals with normal physical activity levels
will be included as absolute controls.

Subjects will report to the university six times and will spend in total about
24 hours at the university (1 screening visit and 5 test days). Subjects will
be asked to fill in different questionnaires and monitor their daily activity
for 5 days. Before test days 2 and 4 subjects will collect a 24 hours urine
sample. During the test day*s subjects will undergo different physical tests to
determine physical function, a maximal exercise test, MRS-measurements of the
upper-leg, a cycling protocol of 60 minutes and an hyperinsulinemic euglycemic
clamp test. Furthermore the subject will under go a total of two muscle
biopsies and two blood draws (from i.v. catheter).
No direct health benefit for the participants is expected. The experimental
procedures are without risks, except for blood sampling and sampling of muscle
biopsies, which can occasionally cause a local hematoma or bruise. The risk of
infection or prolonged bleeding is low due to state of the art technique and
sterility measures. The maximal exercise test and cycling protocol can cause
muscle soreness. During the hyperinsuline euglycemic clamp the risk to develop
hypoglycaemia is rather low, because of the well-experienced researchers
performing this test. Measurements performed during the time course of the
study can potentially lead to coincidental medical findings. Subjects will be
informed about such a finding and possible advised to contact a doctor about
this.