Journal
BIOMOLECULES
Volume 11, Issue 2, Pages -Publisher
MDPI
DOI: 10.3390/biom11020235
Keywords
ageing; tissue-specific; metabolomics; biomarker
Categories
Funding
- Austrian Science Fund (FWF) [P28854, I3792, DK-MCD W1226]
- Austrian Research Promotion Agency (FFG) [864690, 870454]
- Integrative Metabolism Research Center Graz
- Austrian Infrastructure Program 2016/2017
- Styrian Government (Zukunftsfonds)
- BioTechMed-Graz (flagship project)
- FWF [SFB F73, W1226, P32400, P30882, DP-iDP DOC 31]
- BioTechMed-Graz flagship project Lipases and Lipid Signaling
- County of Styria
- City of Graz
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The dysregulation of cellular metabolism is a irreversible hallmark of ageing, with each tissue having a unique metabolic fingerprint that could serve as potential universal biomarkers of ageing. Further exploration of these metabolic changes could provide novel therapeutic targets for the treatment of ageing and age-related diseases, and accurately assessing the age of individuals based on identified metabolite biomarkers.
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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