Oksana V. Kuzniak

Every-other-day fasting (EODF) is one type of caloric restriction that is proposed to have significant health benefits, including slowing aging-related processes. The present study evaluated multiple parameters of blood homeostasis comparing mice of different ages and mice on different diet regimes: ad libitum (AL) versus EODF. Hematological and classical biochemical parameters of blood were measured in young (6-month), middle-aged (12-month) and old (18-month) C57BL/6J mice of both sexes subjected either to EODF, or AL feeding. Middle-aged AL males showed a decrease in erythrocyte and total leucocyte counts and an increase in plasma alkaline phosphatase activity, whereas old animals showed a decrease in relative levels of lymphocytes and an increase in relative levels of neutrophils, a decrease in plasma lactate and an increase in total cholesterol levels, compared to young mice. AL-fed females demonstrated higher stability of blood parameters during aging than males did. The EODF regimen did not significantly affect hematological parameters in females but prevented a decline in total leukocyte count with age in males. In both sexes, EODF partially prevented age-associated changes in levels of plasma lactate and cholesterol and activity of alkaline phosphatase. Thus, during normal aging, mice showed a sex-dependent maintenance of blood homeostasis which was not significantly affected by EODF.

Intermittent fasting as a dietary intervention can prevent overweight and obesity in adult organisms. Nevertheless, information regarding consequences of intermittent fasting for redox status and reactive metabolite-mediated processes that are crucial for the normal functioning of organisms is limited. Since the information on effects of intermittent fasting on parameters of oxidative/carbonyl stress in the brains of young mice was absent, the present study addressed these questions using an every-other-day fasting (EODF) protocol. The levels of carbonyl proteins were ~28 %, 22 % and 18 % lower in the cerebral cortex of EODF males and females and middle parts of the brain of EODF males, respectively, as compared to their ad libitum fed counterparts. Lipid peroxides and α-dicarbonyl compounds were lower only in the cortex and medulla part of EODF male brain. The EODF regimen resulted in higher total non-specific antioxidant capacity in different parts of male brain and a tendency to be higher this parameter in females. At the same time, EODF regimen had no effect on the activities of the defensive antioxidant enzymes, namely superoxide dismutase, catalase, glutathione-S-transferase, glutathione peroxidase, glyoxylase 1 and glucose-6-phosphate dehydrogenase in the cortex of both sexes, but even decreased activities of these enzymes in medulla and middle part of the brain. In general, the results suggest that in the brain of young mice ad libitum feeding induces mild oxidative/carbonyl stress which may be partially alleviated by the EODF regimen. The effect of EODF regimen is more pronounced in the medulla part than in the cortex.

Intermittent fasting is used to reduce body mass in obese adult humans and animals. However, information on the impact of one type of intermittent fasting (IF) called every-other-day feeding (EODF) on young animals is scarce. In this study, one-month-old mice of both sexes were subjected to a four week regimen of EODF using age-matched counterparts fed ad libitum as controls. At the end of EODF exposure, experimental male and female mice weighed 14% and 13% less than the control counterparts. The EODF regimen resulted in lower liver levels of glycogen, glucose, and lactate, but did not affect lactate level in mouse cerebral cortex of both sexes. Activities of key glycolytic enzymes (hexokinase, phosphofructokinase, pyruvate kinase) in liver of experimental mice were lower than those in controls. In the cerebral cortex only hexokinase and pyruvate kinase activities were lower than in controls, but phosphofructokinase activity was not affected in IF females and was higher in IF males as compared with ad libitum fed males. Mitochondria isolated from liver of IF mice had lower respiratory control ratios, but those from the cortex had the same value as control animals. The concentration of beta-hydroxybutyrate and the activity of beta-hydroxybutyrate dehydrogenase were lower in the IF mouse liver, but not changed or enhanced in the IF cerebral cortex. Thus, animal responses to IF do not depend significantly on sex and are directed to decrease energy metabolism to save resources, and the effects are more pronounced in the liver than in the brain.