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Tissue-Specific Landscape of Metabolic Dysregulation during Ageing

Zhang, Fangrong ; Kerbl-Knapp, Jakob ; Akhmetshina, Alena ; Korbelius, Melanie ; Kuentzel, Katharina Barbara LU orcid ; Vujić, Nemanja ; Hörl, Gerd ; Paar, Margret ; Kratky, Dagmar and Steyrer, Ernst , et al. (2021) In Biomolecules 11(2).
Abstract

The dysregulation of cellular metabolism is a hallmark of ageing. To understand the metabolic changes that occur as a consequence of the ageing process and to find biomarkers for age-related diseases, we conducted metabolomic analyses of the brain, heart, kidney, liver, lung and spleen in young (9-10 weeks) and old (96-104 weeks) wild-type mice [mixed genetic background of 129/J and C57BL/6] using NMR spectroscopy. We found differences in the metabolic fingerprints of all tissues and distinguished several metabolites to be altered in most tissues, suggesting that they may be universal biomarkers of ageing. In addition, we found distinct tissue-clustered sets of metabolites throughout the organism. The associated metabolic changes may... (More)

The dysregulation of cellular metabolism is a hallmark of ageing. To understand the metabolic changes that occur as a consequence of the ageing process and to find biomarkers for age-related diseases, we conducted metabolomic analyses of the brain, heart, kidney, liver, lung and spleen in young (9-10 weeks) and old (96-104 weeks) wild-type mice [mixed genetic background of 129/J and C57BL/6] using NMR spectroscopy. We found differences in the metabolic fingerprints of all tissues and distinguished several metabolites to be altered in most tissues, suggesting that they may be universal biomarkers of ageing. In addition, we found distinct tissue-clustered sets of metabolites throughout the organism. The associated metabolic changes may reveal novel therapeutic targets for the treatment of ageing and age-related diseases. Moreover, the identified metabolite biomarkers could provide a sensitive molecular read-out to determine the age of biologic tissues and organs and to validate the effectiveness and potential off-target effects of senolytic drug candidates on both a systemic and tissue-specific level.

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publishing date
type
Contribution to journal
publication status
published
keywords
Aging/metabolism, Animals, Biomarkers/metabolism, Brain/metabolism, Female, Kidney/metabolism, Liver/metabolism, Lung/metabolism, Magnetic Resonance Spectroscopy/methods, Metabolomics/methods, Mice, Mice, Inbred C57BL, Myocardium/metabolism, Spleen/metabolism
in
Biomolecules
volume
11
issue
2
article number
235
publisher
MDPI AG
external identifiers
  • scopus:85100517285
  • pmid:33562384
ISSN
2218-273X
DOI
10.3390/biom11020235
language
English
LU publication?
no
id
38528831-e5c3-4af1-b375-9baf2b56aea9
date added to LUP
2022-10-10 16:27:40
date last changed
2024-07-11 16:58:22
@article{38528831-e5c3-4af1-b375-9baf2b56aea9,
  abstract     = {{<p>The dysregulation of cellular metabolism is a hallmark of ageing. To understand the metabolic changes that occur as a consequence of the ageing process and to find biomarkers for age-related diseases, we conducted metabolomic analyses of the brain, heart, kidney, liver, lung and spleen in young (9-10 weeks) and old (96-104 weeks) wild-type mice [mixed genetic background of 129/J and C57BL/6] using NMR spectroscopy. We found differences in the metabolic fingerprints of all tissues and distinguished several metabolites to be altered in most tissues, suggesting that they may be universal biomarkers of ageing. In addition, we found distinct tissue-clustered sets of metabolites throughout the organism. The associated metabolic changes may reveal novel therapeutic targets for the treatment of ageing and age-related diseases. Moreover, the identified metabolite biomarkers could provide a sensitive molecular read-out to determine the age of biologic tissues and organs and to validate the effectiveness and potential off-target effects of senolytic drug candidates on both a systemic and tissue-specific level.</p>}},
  author       = {{Zhang, Fangrong and Kerbl-Knapp, Jakob and Akhmetshina, Alena and Korbelius, Melanie and Kuentzel, Katharina Barbara and Vujić, Nemanja and Hörl, Gerd and Paar, Margret and Kratky, Dagmar and Steyrer, Ernst and Madl, Tobias}},
  issn         = {{2218-273X}},
  keywords     = {{Aging/metabolism; Animals; Biomarkers/metabolism; Brain/metabolism; Female; Kidney/metabolism; Liver/metabolism; Lung/metabolism; Magnetic Resonance Spectroscopy/methods; Metabolomics/methods; Mice; Mice, Inbred C57BL; Myocardium/metabolism; Spleen/metabolism}},
  language     = {{eng}},
  month        = {{02}},
  number       = {{2}},
  publisher    = {{MDPI AG}},
  series       = {{Biomolecules}},
  title        = {{Tissue-Specific Landscape of Metabolic Dysregulation during Ageing}},
  url          = {{http://dx.doi.org/10.3390/biom11020235}},
  doi          = {{10.3390/biom11020235}},
  volume       = {{11}},
  year         = {{2021}},
}