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,¶1

,§,
1
* Departments of Nutritional Sciences,
Pathology and Laboratory Medicine,
Medicine, and the
§ Wisconsin Regional Primate Research Center, University of Wisconsin, Madison, Wisconsin 53705, USA;
¶ Pathology and Laboratory Medicine Service and

Geriatric Research, Education and Clinical Center, William S. Middleton VA Hospital, Madison, Wisconsin 53705, USA;

Obesity Research Center, St. Lukes/Roosevelt Hospital, Columbia University College of Physicians & Surgeons, New York, New York; and
** Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA
1Correspondence: T.D.O., Pathology and Laboratory Medicine Service, Room A35, William S. Middleton Memorial Veterans Hospital, 2500 Overlook Terr., Madison, WI 53705, USA. E-mail: toberley{at}facstaff.wisc.edu; R.W., Department of Medicine, William S. Middleton Memorial Veterans Hospital (GRECC 4D), 2500 Overlook Terr., Madison, WI 53705, USA. E-mail: rhweindr{at}facstaff.wisc.edu
In laboratory rodents, caloric restriction (CR) retards several
age-dependent physiological and biochemical changes in skeletal muscle,
including increased steady-state levels of oxidative damage to lipids,
DNA, and proteins. We used immunogold electron microscopic (EM)
techniques with antibodies raised against 4-hydroxy-2-nonenal (HNE)
-modified proteins, dinitrophenol, and nitrotyrosine to quantify and
localize the age-dependent accrual of oxidative damage in rhesus monkey
vastus lateralis skeletal muscle. Using immunogold EM analysis of
muscle from rhesus monkeys ranging in age from 2 to 34 years old, a
fourfold maximal increase in levels of HNE-modified proteins was
observed. Likewise, carbonyl levels increased
twofold with
aging. Comparing 17- to 23-year-old normally fed to age-matched monkeys
subjected to CR for 10 years, levels of HNE-modified proteins,
carbonyls, and nitrotyrosine in skeletal muscle from the CR group were
significantly less than control group values. Oxidative damage largely
localized to myofibrils, with lesser labeling in other subcellular
compartments. Accumulation of lipid peroxidation-derived aldehydes,
such as malondialdehyde and 4-hydroxy-2-alkenals, and protein carbonyls
were measured biochemically and confirmed the morphological data. Our
study is the first to quantify morphologically and localize the
age-dependent accrual of oxidative damage in mammalian skeletal muscle
and to demonstrate that oxidative damage in primates is lowered by
CR.Zainal, T. A., Oberley, T. D., Allison, D. B.,
Szweda, L. I., Weindruch, R. Caloric restriction of rhesus monkeys
lowers oxidative damage in skeletal muscle.
Key Words: aging free radicals immunogold lipid peroxidation reactive oxygen species sarcopenia
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