Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Tissue-Specific Landscape of Metabolic Dysregulation During Ageing

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.

Journal reference: Biomolecules 2021, 11, 235
DOI: 10.3390/biom11020235

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.

Subject Areas

ageing; metabolomics; biomarker.; nmr spectroscopy

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