Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Tissue-Specific Landscape of Metabolic Dysregulation During Ageing

Fangrong Zhang
ORCID logo ,
Jakob Kerbl-Knapp
,
Alena Akhmetshina
,
Melanie Korbelius
,
Katharina Küntzel
,
Nemanja Vujic
,
Gerd Hörl
,
Margret Paar
,
Dagmar Kratky
ORCID logo ,
Ernst Steyrer
,
Tobias Madl
* ORCID logo
Version 1 : Received: 6 December 2020 / Approved: 7 December 2020 / Online: 7 December 2020 (15:46:43 CET)

A peer-reviewed article of this Preprint also exists.

Zhang, F.; Kerbl-Knapp, J.; Akhmetshina, A.; Korbelius, M.; Kuentzel, K.B.; Vujić, N.; Hörl, G.; Paar, M.; Kratky, D.; Steyrer, E.; Madl, T. Tissue-Specific Landscape of Metabolic Dysregulation during Ageing. Biomolecules 2021, 11, 235. Zhang, F.; Kerbl-Knapp, J.; Akhmetshina, A.; Korbelius, M.; Kuentzel, K.B.; Vujić, N.; Hörl, G.; Paar, M.; Kratky, D.; Steyrer, E.; Madl, T. Tissue-Specific Landscape of Metabolic Dysregulation during Ageing. Biomolecules 2021, 11, 235.

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 a metabolomic analysis of brain, heart, kidney, liver, lung and spleen in young (9-10 weeks) and old (96-104 weeks) wild type (mixed genetic background of 129/J and C57BL/6) mice using NMR spectroscopy. We found differences in metabolic fingerprints of all tissues and identified 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 age determine the age of biologic tissues and to validate the effectiveness and potential off-target effects of senolytic drug candidates on both a systemic and tissue-specific level.

Keywords

ageing; metabolomics; biomarker.; nmr spectroscopy

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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