Middle age as a turning point in mouse cerebral cortex energy and redox metabolism: Modulation by every-other-day fasting

Maria M Bayliak; Oksana M Sorochynska; Oksana V Kuzniak; Dmytro V Gospodaryov; Oleh I Demianchuk; Yulia V Vasylyk; Nadia M Mosiichuk; Kenneth B Storey; Olga Garaschuk; Volodymyr I Lushchak

doi:10.1016/j.exger.2020.111182

Middle age as a turning point in mouse cerebral cortex energy and redox metabolism: Modulation by every-other-day fasting

Exp Gerontol. 2021 Mar:145:111182. doi: 10.1016/j.exger.2020.111182. Epub 2020 Dec 5.

Affiliations

¹ Department of Biochemistry and Biotechnology, Vasyl Stefanyk Precarpathian National University, 57 Shevchenko Str., Ivano-Frankivsk 76018, Ukraine.
² Department of Biology, Carleton University, 1125 Colonel By Drive, Ottawa, Ontario K1S 5B6, Canada.
³ Department of Neurophysiology, University of Tübingen, 72074 Tübingen, Germany.
⁴ Department of Biochemistry and Biotechnology, Vasyl Stefanyk Precarpathian National University, 57 Shevchenko Str., Ivano-Frankivsk 76018, Ukraine. Electronic address: volodymyr.lushchak@pnu.edu.ua.

PMID: 33290862
DOI: 10.1016/j.exger.2020.111182

Abstract

Normal brain aging is accompanied by intensification of free radical processes and compromised bioenergetics. Caloric restriction is expected to counteract these changes but the underlying protective mechanisms remain poorly understood. The present work aimed to investigate the intensity of oxidative stress and energy metabolism in the cerebral cortex comparing mice of different ages as well as comparing mice given one of two regimens of food availability: ad libitum versus every-other-day fasting (EODF). Levels of oxidative stress markers, ketone bodies, glycolytic intermediates, mitochondrial respiration, and activities of antioxidant and glycolytic enzymes were assessed in cortex from 6-, 12- and 18-month old C57BL/6J mice. The greatest increase in oxidative stress markers and the sharpest decline in key glycolytic enzyme activities was observed in mice upon the transition from young (6 months) to middle (12 months) age, with smaller changes occurring upon transition to old-age (18 months). Brain mitochondrial respiration showed no significant changes with age. A decrease in the activities of key glycolytic enzymes was accompanied by an increase in the activity of glucose-6-phosphate dehydrogenase suggesting that during normal brain aging glucose metabolism is altered to lower glycolytic activity and increase dependence on the pentose-phosphate pathway. Interestingly, levels of ketone bodies and antioxidant capacity showed a greater decrease in the brain cortex of females as compared with males. The EODF regimen further suppressed glycolytic enzyme activities in the cortex of old mice, and partially enhanced oxygen consumption and respiratory control in the cortex of middle aged and old males. Thus, in the mammalian cortex the major aging-induced metabolic changes are already seen in middle age and are slightly alleviated by an intermittent fasting mode of feeding.

Keywords: Aging; Antioxidant enzymes; Cerebral cortex; Glycolytic enzymes; Mitochondrial respiration; Pentose phosphate pathway.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aging
Animals
Cerebral Cortex
Energy Metabolism
Fasting*
Female
Male
Mice
Mice, Inbred C57BL
Oxidation-Reduction
Pentose Phosphate Pathway*