Metabolic drift in the aging nervous system is reflected in human cerebrospinal fluid

Abstract Chronic diseases affecting the central nervous system (CNS) like Alzheimer’s or Parkinson’s disease typically develop with advanced chronological age. Yet, aging at the metabolic level has been explored only sporadically in humans using biofluids in close proximity to the CNS such as the ce...

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Autores principales:	Kristian Peters, Stephanie Herman, Payam Emami Khoonsari, Joachim Burman, Steffen Neumann, Kim Kultima
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5882fcde31ea44aca5247d8eacedbba8
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spelling	oai:doaj.org-article:5882fcde31ea44aca5247d8eacedbba82021-12-02T15:15:14ZMetabolic drift in the aging nervous system is reflected in human cerebrospinal fluid10.1038/s41598-021-97491-12045-2322https://doaj.org/article/5882fcde31ea44aca5247d8eacedbba82021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97491-1https://doaj.org/toc/2045-2322Abstract Chronic diseases affecting the central nervous system (CNS) like Alzheimer’s or Parkinson’s disease typically develop with advanced chronological age. Yet, aging at the metabolic level has been explored only sporadically in humans using biofluids in close proximity to the CNS such as the cerebrospinal fluid (CSF). We have used an untargeted liquid chromatography high-resolution mass spectrometry (LC-HRMS) based metabolomics approach to measure the levels of metabolites in the CSF of non-neurological control subjects in the age of 20 up to 74. Using a random forest-based feature selection strategy, we extracted 69 features that were strongly related to age (p age < 0.001, rage = 0.762, R2 Boruta age = 0.764). Combining an in-house library of known substances with in silico chemical classification and functional semantic annotation we successfully assigned putative annotations to 59 out of the 69 CSF metabolites. We found alterations in metabolites related to the Cytochrome P450 system, perturbations in the tryptophan and kynurenine pathways, metabolites associated with cellular energy (NAD+, ADP), mitochondrial and ribosomal metabolisms, neurological dysfunction, and an increase of adverse microbial metabolites. Taken together our results point at a key role for metabolites found in CSF related to the Cytochrome P450 system as most often associated with metabolic aging.Kristian PetersStephanie HermanPayam Emami KhoonsariJoachim BurmanSteffen NeumannKim KultimaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kristian Peters Stephanie Herman Payam Emami Khoonsari Joachim Burman Steffen Neumann Kim Kultima Metabolic drift in the aging nervous system is reflected in human cerebrospinal fluid
description	Abstract Chronic diseases affecting the central nervous system (CNS) like Alzheimer’s or Parkinson’s disease typically develop with advanced chronological age. Yet, aging at the metabolic level has been explored only sporadically in humans using biofluids in close proximity to the CNS such as the cerebrospinal fluid (CSF). We have used an untargeted liquid chromatography high-resolution mass spectrometry (LC-HRMS) based metabolomics approach to measure the levels of metabolites in the CSF of non-neurological control subjects in the age of 20 up to 74. Using a random forest-based feature selection strategy, we extracted 69 features that were strongly related to age (p age < 0.001, rage = 0.762, R2 Boruta age = 0.764). Combining an in-house library of known substances with in silico chemical classification and functional semantic annotation we successfully assigned putative annotations to 59 out of the 69 CSF metabolites. We found alterations in metabolites related to the Cytochrome P450 system, perturbations in the tryptophan and kynurenine pathways, metabolites associated with cellular energy (NAD+, ADP), mitochondrial and ribosomal metabolisms, neurological dysfunction, and an increase of adverse microbial metabolites. Taken together our results point at a key role for metabolites found in CSF related to the Cytochrome P450 system as most often associated with metabolic aging.
format	article
author	Kristian Peters Stephanie Herman Payam Emami Khoonsari Joachim Burman Steffen Neumann Kim Kultima
author_facet	Kristian Peters Stephanie Herman Payam Emami Khoonsari Joachim Burman Steffen Neumann Kim Kultima
author_sort	Kristian Peters
title	Metabolic drift in the aging nervous system is reflected in human cerebrospinal fluid
title_short	Metabolic drift in the aging nervous system is reflected in human cerebrospinal fluid
title_full	Metabolic drift in the aging nervous system is reflected in human cerebrospinal fluid
title_fullStr	Metabolic drift in the aging nervous system is reflected in human cerebrospinal fluid
title_full_unstemmed	Metabolic drift in the aging nervous system is reflected in human cerebrospinal fluid
title_sort	metabolic drift in the aging nervous system is reflected in human cerebrospinal fluid
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/5882fcde31ea44aca5247d8eacedbba8
work_keys_str_mv	AT kristianpeters metabolicdriftintheagingnervoussystemisreflectedinhumancerebrospinalfluid AT stephanieherman metabolicdriftintheagingnervoussystemisreflectedinhumancerebrospinalfluid AT payamemamikhoonsari metabolicdriftintheagingnervoussystemisreflectedinhumancerebrospinalfluid AT joachimburman metabolicdriftintheagingnervoussystemisreflectedinhumancerebrospinalfluid AT steffenneumann metabolicdriftintheagingnervoussystemisreflectedinhumancerebrospinalfluid AT kimkultima metabolicdriftintheagingnervoussystemisreflectedinhumancerebrospinalfluid
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Metabolic drift in the aging nervous system is reflected in human cerebrospinal fluid

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