Parabiosis Incompletely Reverses Aging-Induced Metabolic Changes and Oxidant Stress in Mouse Red Blood Cells

Evan J. Morrison, Devin P. Champagne, Monika Dzieciatkowska, Travis Nemkov, James C. Zimring, Kirk C. Hansen, Fangxia Guan, Derek M. Huffman, Laura Santambrogio, Angelo D'Alessandro

Research output: Contribution to journalArticle

Abstract

Mature red blood cells (RBCs) not only account for ~83% of the total host cells in the human body, but they are also exposed to all body tissues during their circulation in the bloodstream. In addition, RBCs are devoid of de novo protein synthesis capacity and, as such, they represent a perfect model to investigate system-wide alterations of cellular metabolism in the context of aging and age-related oxidant stress without the confounding factor of gene expression. In the present study, we employed ultra-high-pressure liquid chromatography coupled with mass spectrometry (UHPLC-MS)-based metabolomics and proteomics to investigate RBC metabolism across age in male mice (6, 15, and 25 months old). We report that RBCs from aging mice face a progressive decline in the capacity to cope with oxidant stress through the glutathione/NADPH-dependent antioxidant systems. Oxidant stress to tryptophan and purines was accompanied by declines in late glycolysis and methyl-group donors, a potential compensatory mechanism to repair oxidatively damaged proteins. Moreover, heterochronic parabiosis experiments demonstrated that the young environment only partially rescued the alterations in one-carbon metabolism in old mice, although it had minimal to no impact on glutathione homeostasis, the pentose phosphate pathway, and oxidation of purines and tryptophan, which were instead aggravated in old heterochronic parabionts.

Original languageEnglish (US)
JournalNutrients
Volume11
Issue number6
DOIs
StatePublished - Jun 14 2019

Fingerprint

Parabiosis
Oxidants
oxidants
erythrocytes
Erythrocytes
Purines
mice
purines
Tryptophan
tryptophan
metabolism
Glutathione
glutathione
Pentose Phosphate Pathway
Metabolomics
pentoses
Cell Aging
metabolomics
glycolysis
Glycolysis

Keywords

  • blood
  • erythrocyte
  • mass spectrometry
  • metabolism
  • metabolomics

ASJC Scopus subject areas

  • Food Science
  • Nutrition and Dietetics

Cite this

Morrison, E. J., Champagne, D. P., Dzieciatkowska, M., Nemkov, T., Zimring, J. C., Hansen, K. C., ... D'Alessandro, A. (2019). Parabiosis Incompletely Reverses Aging-Induced Metabolic Changes and Oxidant Stress in Mouse Red Blood Cells. Nutrients, 11(6). https://doi.org/10.3390/nu11061337

Parabiosis Incompletely Reverses Aging-Induced Metabolic Changes and Oxidant Stress in Mouse Red Blood Cells. / Morrison, Evan J.; Champagne, Devin P.; Dzieciatkowska, Monika; Nemkov, Travis; Zimring, James C.; Hansen, Kirk C.; Guan, Fangxia; Huffman, Derek M.; Santambrogio, Laura; D'Alessandro, Angelo.

In: Nutrients, Vol. 11, No. 6, 14.06.2019.

Research output: Contribution to journalArticle

Morrison, EJ, Champagne, DP, Dzieciatkowska, M, Nemkov, T, Zimring, JC, Hansen, KC, Guan, F, Huffman, DM, Santambrogio, L & D'Alessandro, A 2019, 'Parabiosis Incompletely Reverses Aging-Induced Metabolic Changes and Oxidant Stress in Mouse Red Blood Cells', Nutrients, vol. 11, no. 6. https://doi.org/10.3390/nu11061337
Morrison EJ, Champagne DP, Dzieciatkowska M, Nemkov T, Zimring JC, Hansen KC et al. Parabiosis Incompletely Reverses Aging-Induced Metabolic Changes and Oxidant Stress in Mouse Red Blood Cells. Nutrients. 2019 Jun 14;11(6). https://doi.org/10.3390/nu11061337
Morrison, Evan J. ; Champagne, Devin P. ; Dzieciatkowska, Monika ; Nemkov, Travis ; Zimring, James C. ; Hansen, Kirk C. ; Guan, Fangxia ; Huffman, Derek M. ; Santambrogio, Laura ; D'Alessandro, Angelo. / Parabiosis Incompletely Reverses Aging-Induced Metabolic Changes and Oxidant Stress in Mouse Red Blood Cells. In: Nutrients. 2019 ; Vol. 11, No. 6.
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