Intermittent fasting can be effective in reducing metabolic disorders and age-related diseases. However, there remain questions about the effects of fasting with respect to the age in which fasting begins, the fasting models, and the mechanisms involved. We investigated the effects of age of beginning fasting and chronic mild and severe fasting models on blood pressure (BP), insulin/glucose profile, and expression of klotho, sirtuin1 (SIRT1), and sirtuin3 (SIRT3) in male Wistar rats. Young (3 months), middle-aged (12 months), and old (22 months) animals were randomly divided into three subgroups and fed as ad libitum (AL), AL with fasting 1 day per week (FW), and AL with fasting every other day (EOD), respectively, for 3 months. The FW reduced the weight gain in young animals (p < 0.001 vs. AL), whereas EOD induced weight loss in all three age categories (p < 0.001). Aging was associated with high BP, high glucose, and insulin levels. Both FW and EOD feedings decreased BP and blood glucose level (p < 0.001) and EOD decreased insulin level (p < 0.05 vs. AL) in old animals. Parallel to aging, the expression of SIRT1 and klotho significantly decreased in plasma and EOD feeding recovered this defect. Both FW and EOD feedings increased the expression of SIRT3 in middle-aged and old rats. Age is a determining factor for the effectiveness of fasting and old animals respond more desirably to fasting. The effect of EOD fasting is more effective than FW fasting in improving the metabolic factors, partly through the recovery of SIRT1 and klotho.
Keywords: age; blood pressure; fasting models; insulin/glucose profile; klotho; sirtuins.