Alteration of soluble adhesion molecules during aging and their modulation by calorie restriction

To investigate the status of soluble adhesion molecules (sAMs) during aging, the present study determined protein levels of several major sAMs in serum samples obtained from rats at different ages. These sAMs include E-selectin, P-selectin, vascular cell adhesion molecule 1 (VCAM-1), and intercellular adhesion molecule 1 (ICAM-1). Fischer 344 rats, ages 6, 12, 18, and 24 months, fed ad libitum (AL) and calorie restricted (CR) diets were used in this study. Analysis by Western blotting showed that the levels of all sAMs studied increased during aging in AL rats, but were effectively blunted in the CR rats. Total reactive oxygen species/reactive nitrogen species (ROS/RNS) levels were measured by fluorescent probe 2',7'-dichlorofluorescin diacetate. Increased ROS/RNS levels were found to coincide with increased levels of superoxide-generating xanthine oxidase in serum during aging, but were found suppressed by CR. Increases in sAMs levels were duplicated in another experiment in which young (13-month-old) and old (31-month-old) rats were injected with proinflammatory lipopolysaccharide. These findings suggest that the altered expressions of sAMs may be due to increased oxidative stress with advanced age and that these increases were prevented by CR through its antioxidative action.