Increased macromolecular damage due to oxidative stress in the neocortex and hippocampus of WNIN/Ob, a novel rat model of premature aging

- WNIN/Ob obese rat is a unique rat strain with metabolic syndrome and reduced lifespan.
- Increased oxidative stress and decreased activity of antioxidant enzymes are seen in the brain of young WNIN/Ob obese rats.
- Early accumulation of DNA damage is found in the neocortex and hippocampus of WNIN/Ob obese rats.
- Onset of macromolecular damage at young age may trigger premature aging in WNIN/Ob obese rats.
- WNIN/Ob obese rat can be used for future studies to decipher the molecular mechanisms underlying premature aging.

Wistar of the National Institute of Nutrition obese (WNIN/Ob) is a unique rat strain isolated and established at NIN, Hyderabad, India, in 1996, from its existing stock of Wistar rat colony (WNIN). This animal model exhibits all traits of metabolic syndrome and has a remarkably reduced lifespan (1.5 years as compared to 3 years in parental WNIN rats), albeit, the factors associated with premature aging are not well understood. Considering that oxidative stress and DNA damage are crucial players associated with senescence, we analyzed oxidative stress markers like lipid peroxidation and protein oxidation; DNA damage in terms of both single-stranded and double-stranded breaks and the activity of antioxidant enzymes: superoxide dismutase and catalase in brain regions of these animals. Our study revealed that the magnitude of oxidative stress and DNA damage in the neocortex and hippocampus of 3-month-old WNIN/Ob obese rats is as high as that seen in 15-month-old parental WNIN control rats. Concurrently, the antioxidant enzyme activity was significantly decreased. From these results, it can be concluded that increased oxidative stress-induced damage of macromolecules, probably due to reduced activity of antioxidant enzymes, is associated with premature aging in WNIN/Ob obese rats.

An early accumulation of macromolecular damage due to oxidative stress in WNIN/Ob obese rats may be associated with the observed short lifespan.77