MUSCLE DAMAGE IN AGING--INFLAMMATORY MECHANISMS

Unaccustomed muscular activity of even moderate intensity results
in a certain amount of damage to contractile proteins and
associated connective tissue. Eccentric exercise, in which muscles
lengthen as they develop tension, is a natural part of most forms
of exercise and is a particularly potent inducer of damage. An
inflammatory response is associated with this muscle damage which
might contribute to catabolic processes and may mediate muscle
protein turn over responsible for repair. We propose to use
eccentric exercise to examine age-related differences in the
inflammatory response associated with muscle damage. The
inflammatory response will be measured in blood and in skeletal
muscle. Circulating immune complexes, functional complement
activity, interleukin-l (IL-l), humor necrosis factor (TNF), and
humoral cytotoxic factors will be measured. In muscle, HLA class
I antigens, IL-l, and TNF concentrations and receptor numbers will
be determined and the immunohistological characterization of
invading leukocytes will be performed. The influence of the non-
steroidal anti-inflammatory drug indomethacin, and the influence
of dietary omega-3 fatty acid supplementation on all of these
parameters will be assessed as well. By examining the systemic and
intramuscular processes involved in damaging exercise, the
mechanisms which may be critically important effectors of repair
and peripheral training in young and old subjects will be
characterized for the first time. This study will bring together
novel methods to examine responses to muscle damage and
differentiate between the young and the old. These data will be
important for the athlete, but perhaps more important for the
millions of old and young people beginning a program of increased
physical activity. Moreover, the eccentric exercise protocol may
prove to be a safe and controlled alternative experimental model
for studying inflammation the elderly.