UC Irvine

It has been proposed that senescence may be associated with changes associated with oxidative damage to macromolecules. Levels of cerebellar nitric oxide synthase (NOS) and rates of generation of cortical reactive oxygen species (ROS), have been determined in mice of various ages. Both of these parameters were significantly reduced in mice aged 9 months relative to 3-month-old mice. In order to determine whether dietary manipulation can modulate these changes, the effect of exposure of mice to differing diets incorporating various antioxidants, was examined. These diets were given to 3-month-old mice for a total period of 6 further months. The presence of melatonin (40 ppm) in the basal diet restored both NOS and ROS levels to the corresponding values found in the younger (3-month-old) group of mice while lipoic acid (1650 ppm) also restored levels of NOS to those found in 3-month-old animals. Addition of coenzyme Q (ubiquinone), 200 ppm or alpha-tocopherol (1000 ppm) to the basal diet had no effect on either NOS levels or ROS generation. These data suggest that dietary supplementation may aid in delaying onset of metabolic changes characteristic of the older brain. In behavioral testing, older (9-month-old) animals exhibited reduced motor activity and diminished recall ability on the second day of exposure to the test paradigm. While no diet altered motor activity or improved recall of older animals, lipoic acid or tocopherol treatment adversely affected place recall familiarity.