Tissue-Specific Landscape of Metabolic Dysregulation during Ageing
Fangrong Zhang,
Jakob Kerbl-Knapp,
Alena Akhmetshina,
Melanie Korbelius,
Katharina Barbara Kuentzel,
Nemanja Vujić,
Gerd Hörl,
Margret Paar,
Dagmar Kratky,
Ernst Steyrer,
Tobias Madl
Affiliations
Fangrong Zhang
Gottfried Schatz Research Center for Cell Signaling, Metabolism and Ageing, Molecular Biology and Biochemistry, Medical University of Graz, 8010 Graz, Austria
Jakob Kerbl-Knapp
Gottfried Schatz Research Center for Cell Signaling, Metabolism and Ageing, Molecular Biology and Biochemistry, Medical University of Graz, 8010 Graz, Austria
Alena Akhmetshina
Gottfried Schatz Research Center for Cell Signaling, Metabolism and Ageing, Molecular Biology and Biochemistry, Medical University of Graz, 8010 Graz, Austria
Melanie Korbelius
Gottfried Schatz Research Center for Cell Signaling, Metabolism and Ageing, Molecular Biology and Biochemistry, Medical University of Graz, 8010 Graz, Austria
Katharina Barbara Kuentzel
Gottfried Schatz Research Center for Cell Signaling, Metabolism and Ageing, Molecular Biology and Biochemistry, Medical University of Graz, 8010 Graz, Austria
Nemanja Vujić
Gottfried Schatz Research Center for Cell Signaling, Metabolism and Ageing, Molecular Biology and Biochemistry, Medical University of Graz, 8010 Graz, Austria
Gerd Hörl
Otto-Loewi Research Center, Physiological Chemistry, Medical University of Graz, 8010 Graz, Austria
Margret Paar
Otto-Loewi Research Center, Physiological Chemistry, Medical University of Graz, 8010 Graz, Austria
Dagmar Kratky
Gottfried Schatz Research Center for Cell Signaling, Metabolism and Ageing, Molecular Biology and Biochemistry, Medical University of Graz, 8010 Graz, Austria
Ernst Steyrer
Gottfried Schatz Research Center for Cell Signaling, Metabolism and Ageing, Molecular Biology and Biochemistry, Medical University of Graz, 8010 Graz, Austria
Tobias Madl
Gottfried Schatz Research Center for Cell Signaling, Metabolism and Ageing, Molecular Biology and Biochemistry, Medical University of Graz, 8010 Graz, Austria
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.
