Universität zu Köln

Annibal, Andrea ORCID: 0000-0003-4311-5417, Tharyan, Rebecca George, Schonewolff, Maribel Fides, Tam, Hannah ORCID: 0000-0002-8445-6798, Latza, Christian, Auler, Markus Max Karl and Antebi, Adam (2021). Regulation of the one carbon folate cycle as a shared metabolic signature of longevity. Nat. Commun., 12 (1). BERLIN: NATURE RESEARCH. ISSN 2041-1723

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Abstract

The metabolome represents a complex network of biological events that reflects the physiologic state of the organism in health and disease. Additionally, specific metabolites and metabolic signaling pathways have been shown to modulate animal ageing, but whether there are convergent mechanisms uniting these processes remains elusive. Here, we used high resolution mass spectrometry to obtain the metabolomic profiles of canonical longevity pathways in C. elegans to identify metabolites regulating life span. By leveraging the metabolomic profiles across pathways, we found that one carbon metabolism and the folate cycle are pervasively regulated in common. We observed similar changes in long-lived mouse models of reduced insulin/IGF signaling. Genetic manipulation of pathway enzymes and supplementation with one carbon metabolites in C. elegans reveal that regulation of the folate cycle represents a shared causal mechanism of longevity and proteoprotection. Such interventions impact the methionine cycle, and reveal methionine restriction as an underlying mechanism. This comparative approach reveals key metabolic nodes to enhance healthy ageing. Metabolic pathways are closely intertwined with longevity. Here the authors perform metabolomic profiling of canonical longevity pathways and show that folate and methionine cycle intermediates are changed in common, and further, genetic manipulation of pathway enzymes and supplementation with metabolites indicates that they causally regulate longevity.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Annibal, Andrea UNSPECIFIED orcid.org/0000-0003-4311-5417 UNSPECIFIED Tharyan, Rebecca George UNSPECIFIED UNSPECIFIED UNSPECIFIED Schonewolff, Maribel Fides UNSPECIFIED UNSPECIFIED UNSPECIFIED Tam, Hannah UNSPECIFIED orcid.org/0000-0002-8445-6798 UNSPECIFIED Latza, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Auler, Markus Max Karl UNSPECIFIED UNSPECIFIED UNSPECIFIED Antebi, Adam UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-572396
DOI:	10.1038/s41467-021-23856-9
Journal or Publication Title:	Nat. Commun.
Volume:	12
Number:	1
Date:	2021
Publisher:	NATURE RESEARCH
Place of Publication:	BERLIN
ISSN:	2041-1723
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language LIFE-SPAN EXTENSION; FOLIC-ACID; METHIONINE RESTRICTION; C. ELEGANS; S-ADENOSYLMETHIONINE; CALORIE RESTRICTION; DIETARY RESTRICTION; METHYLATION; BENEFIT; PATHWAY Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/57239