Caloric restriction of rhesus monkeys lowers oxidative damage in
skeletal muscle
T.D. Oberley, T.A. Zainal, D.B. Allison, L.I. Szweda, R. Weindruch
Department of Pathology and Laboratory Medicine
University of Wisconsin Medical School
Madison, WI 53706
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 accumulation of oxidative damage in rhesus monkey 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 caloric restriction (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, and protein carabonyls 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.
KEY WORDS:
Aging, free radicals, lipid peroxidation, reactive oxygen species,
sarcopenia
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