ACUTE EXERCISE STIMULATES ANTIOXIDANT DEFENSE IN SKELETAL MUSCLE IN AGING-DELAYED AMES DWARF MOUSE
M.A. Romanick, S.G. Rakoczy, H.M. Brown-Borg
Department of Pharmacology, Physiology, and Therapeutics
University of North Dakota
P.O. Box 9037
Grand Forks, ND 58202-9037
The aging phenomenon is influenced by the degree to which
oxidative stress is experienced. The Ames dwarf mouse has
demonstrated delayed aging with evidence that this mammal
with endocrine deficiencies of growth hormone, thyrotropin,
and prolactin has a heightened defense against oxidative
stress challenges in a variety of tissues, such as liver,
kidney, heart, and brain. Skeletal muscle is a tissue that
also demonstrates clear signs of aging, such as sarcopenia,
strength loss, and contractile property changes. Unlike
many tissues, muscle is postmitotic; therefore, muscle
fibers receive a continuous onslaught of oxidative stress
throughout life. This experiment examined antioxidant
enzyme activity and antioxidant substrate availability in
3-, 12-, and 20-month-old dwarf and wild type mouse skeletal
muscle following a 1-hour exercise bout of swimming. A
metabolic challenge of this type to skeletal muscle will
increase oxygen consumption with a resultant increase in
oxidative stress exposure. Spectrophotometric assays were
performed on hindlimb skeletal muscle tissue from dwarf and
wild type mice which were swum for one hour in a 32ºC water
bath. Activity of antioxidant enzymes, catalase (CAT) and
glutathione peroxidase (GPX), were measured along with the
concentration of reduced (GSH) and oxidized (GSSG)
glutathione, all playing a significant role in removing
reactive oxygen species from the cell. GPX activity was
measured in both exercised and nonexercised animals. In
muscle tissues of exercised mice, CAT activity was not
significantly different between dwarf and wild type animals.
In addition, no age effect on CAT activity was seen.
Previous CAT activity data with nonexercised mice produced
similar results. Differences observed in GPX activity were
seen between lines, ages, and exercise types. GPX activity
in wild type sedentary mice remained essentially unchanged
with age; however, this activity was increased early in life
in exercised mice but decreased with age. Exercised dwarf
mice maintained steady GPX activity with age. All dwarf
mice exhibited heightened GPX activity with age, which
expressed itself to an even greater extent at the oldest age
(20 months) when exercised. Maintenance of GPX activity
levels in the aging dwarf mouse may indicate a mechanism to
combat the oxidative stress that accumulates with time.
Although GSH levels in acutely exercised dwarf mice
decreased with age, the ratio of reduced to oxidized
glutathione remained steady with age, keeping the recycling
of GSSG to antioxidant GSH at a consistent level. These
data indicate that aging dwarf mice in comparison to wild
type mice demonstrate a certain level of heightened GPX
activity response and show an even more pronounced response
when exposed to increased exercise activity. Future studies
will examine antioxidant defense following a 6-week daily
swim. It is anticipated that the Ames dwarf mouse will
continue to demonstrate increased defense relative to
oxidative stress challenge.
Key words:
skeletal muscle, aging, oxidative stress
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