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Middle aged turn point in parameters of oxidative stress and glucose catabolism in mouse cerebellum during lifespan: minor effects of every-other-day fasting

Abstract

The cerebellum is considered to develop aging markers more slowly than other parts of the brain. Intensification of free radical processes and compromised bioenergetics, critical hallmarks of normal brain aging, may be slowed down by caloric restriction. This study aimed to evaluate the intensity of oxidative stress and the enzymatic potential to utilize glucose via glycolysis or the pentose phosphate pathway (PPP) in the cerebellum of mice under ad libitum versus every-other-day fasting (EODF) feeding regimens. Levels of lipid peroxides, activities of antioxidant and key glycolytic and PPP enzymes were measured in young (6-month), middle-aged (12-month) and old (18-month) C57BL/6J mice. The cerebellum showed the most dramatic increase in lipid peroxide levels, antioxidant capacity and PPP key enzyme activities and the sharpest decline in the activities of key glycolytic enzymes under transition from young to middle age but these changes slowed when transiting from middle to old age. A decrease in the activity of the key glycolytic enzyme phosphofructokinase was accompanied by a concomitant increase in the activities of hexokinase and glucose-6-phosphate dehydrogenase (G6PDH), which may suggest that during normal cerebellar aging glucose metabolism shifts from glycolysis to the pentose phosphate pathway. The data indicate that intensification of free radical processes in the cerebellum occurred by middle age and that activation of the PPP together with increased antioxidant capacity can help to resist these changes into old age. However, the EODF regime did not significantly modulate or alleviate any of the metabolic processes studied in this analysis of the aging cerebellum.

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The data supporting the findings of this study are available on the request.

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Abbreviations

AL:

ad libitum

EODF:

Every-other-day fasting

G6PDH:

Glucose-6-phosphate dehydrogenase

GPx:

Glutathione peroxidase

GR:

Glutathione reductase

GST:

Glutathione-S-transferase

HK:

Hexokinase

KPi:

Potassium phosphate buffer

LDH:

Lactate dehydrogenase

LOOH:

Lipid peroxides

PFK:

Phosphofructokinase

PK:

Pyruvate kinase

PPP:

Pentose phosphate pathway

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Acknowledgements

We thank our students T. Pankiv and A. Klonovsky for technical assistance with biochemical measurements. This work was mainly supported by a grant from the Volkswagen Foundation (VolkswagenStiftung, #90233), Germany, to OG and VIL, and partially by a Ministry of Education and Science of Ukraine grant (#0118U003477) to VIL, and a Discovery grant from the Natural Sciences and Engineering Research Council of Canada (#6793) to KBS.

Funding

This work was mainly supported by the grant from Volkswagen Foundation (VolkswagenStiftung, #90233), Germany, to VIL and OG, partially by a Ministry of Education and Science of Ukraine grant (#0118U003477) to VIL, and by a Discovery grant from the Natural Sciences and Engineering Research Council of Canada (#6793) to KBS.

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Correspondence to Volodymyr I. Lushchak.

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The authors declare that they have no conflict of interest.

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All mouse protocols were approved by the Animal Experimental Committee of Vasyl Stefanyk Precarpathian National University (Ukraine) and were conducted in accordance with the European Communities Council Directives of 24 November 1986 (86/609/ECC). The manuscript does not contain clinical studies or patient data.

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Bayliak, M.M., Mosiichuk, N.M., Sorochynska, O.M. et al. Middle aged turn point in parameters of oxidative stress and glucose catabolism in mouse cerebellum during lifespan: minor effects of every-other-day fasting. Biogerontology 22, 315–328 (2021). https://doi.org/10.1007/s10522-021-09918-x

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  • DOI: https://doi.org/10.1007/s10522-021-09918-x

Keywords

  • Antioxidant enzymes
  • Aging
  • Brain
  • Glycolysis
  • Glucose-6-phosphate dehydrogenase
  • Lipid peroxides
  • Phosphofructokinase