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Effect of age and caloric restriction on DNA oxidative damage in different tissues of C57BL/6 mice
R S Sohal1, S Agarwal, M Candas
1Department of Biological Sciences, Southern Methodist University, Dallas, TX 75275.
Abstract:
The objective of this study was to explore the role of molecular oxidative damage and caloric intake in the aging process. The concentration of 8-hydroxydeoxyguanosine (8-OHdG), a product of DNA oxidation, was compared in five different tissues of mice (skeletal muscle, brain, heart, liver and kidney) as a function of age and in response to dietary restriction. A comparison of 8- and 27-month-old mice indicated that the age-related increase in 8-OHdG concentration was greater in skeletal muscle, brain and heart, which are primarily composed of long-lived, post-mitotic cells, than in liver and kidney, which consist of slow-dividing cells. Dietary restricted (DR) mice kept on 60% caloric intake as compared to the ad libitum-fed (AL) mice showed a lower concentration in 8-OHdG content in all the tissues compared to AL mice. The DR-related amelioration of DNA oxidative damage was greater in the post-mitotic tissues compared to those undergoing slow mitoses. Results support the hypothesis that oxidative damage to long-lived post-mitotic cells may be a key factor in the aging process.
Insights
Oxidative damage, measured by 8-hydroxydeoxyguanosine (8-OHdG), increases with age, especially in long-lived cells. Dietary restriction reduces this damage, suggesting a key role for oxidative stress in aging.
Area of Science:
- Gerontology
- Molecular Biology
- Biochemistry
Background:
- Aging is associated with molecular oxidative damage.
- 8-hydroxydeoxyguanosine (8-OHdG) is a biomarker of DNA oxidation.
- Cellular composition (post-mitotic vs. dividing) may influence aging processes.
Purpose of the Study:
- To investigate the link between oxidative damage and aging.
- To determine the impact of caloric intake on DNA oxidation.
- To compare oxidative damage levels in different mouse tissues.
Main Methods:
- Measured 8-OHdG concentrations in skeletal muscle, brain, heart, liver, and kidney of mice.
- Compared 8-OHdG levels in young (8-month) versus old (27-month) mice.
- Assessed the effect of dietary restriction (60% caloric intake) versus ad libitum feeding on 8-OHdG levels.
Main Results:
- Age-related 8-OHdG increase was higher in post-mitotic tissues (skeletal muscle, brain, heart) than in slow-dividing tissues (liver, kidney).
- Dietary restricted mice exhibited lower 8-OHdG concentrations across all tissues compared to ad libitum-fed mice.
- Dietary restriction's protective effect against oxidative damage was more pronounced in post-mitotic tissues.
Conclusions:
- Oxidative damage to long-lived, post-mitotic cells is a significant factor in aging.
- Dietary restriction mitigates oxidative DNA damage, potentially slowing the aging process.
- Tissue-specific differences in cell turnover rates influence susceptibility to age-related oxidative damage.