Related Experiment Videos
Caloric restriction of rhesus monkeys lowers oxidative damage in skeletal muscle
T A Zainal1, T D Oberley, D B Allison
1Departments of Nutritional Sciences, Pathology and Laboratory Medicine, Medicine, Wisconsin Regional Primate Research Center, University of Wisconsin, Madison, Wisconsin 53705, USA.
Abstract:
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 approximately 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.
Insights
Caloric restriction (CR) in primates significantly reduces age-related oxidative damage in skeletal muscle. This study quantifies and localizes this damage, showing CR lowers markers like HNE-modified proteins and carbonyls.
Area of Science:
- Aging research
- Skeletal muscle physiology
- Oxidative stress
Background:
- Caloric restriction (CR) in rodents slows aging and reduces muscle oxidative damage.
- Age-dependent oxidative damage accumulates in skeletal muscle, affecting lipids, DNA, and proteins.
Purpose of the Study:
- To quantify and localize age-dependent oxidative damage in rhesus monkey skeletal muscle.
- To investigate the effect of CR on oxidative damage markers in primate skeletal muscle.
Main Methods:
- Immunogold electron microscopy (EM) using antibodies against 4-hydroxy-2-nonenal (HNE)-modified proteins, dinitrophenol, and nitrotyrosine.
- Biochemical assays for malondialdehyde, 4-hydroxy-2-alkenals, and protein carbonyls.
- Analysis of skeletal muscle from rhesus monkeys aged 2-34 years, including a CR group.
Main Results:
- A fourfold increase in HNE-modified proteins and a twofold increase in carbonyls were observed with aging.
- CR significantly reduced levels of HNE-modified proteins, carbonyls, and nitrotyrosine compared to controls.
- Oxidative damage was primarily localized to myofibrils in skeletal muscle.
Conclusions:
- This is the first study to morphologically quantify and localize age-dependent oxidative damage in mammalian skeletal muscle.
- Caloric restriction demonstrably lowers oxidative damage in primate skeletal muscle, suggesting a potential anti-aging intervention.