Regulation of the one carbon folate cycle as a shared metabolic signature of 
longevity

Annibal, A.; Tharyan, R. G.; Schonewolff, M. F.; Tam, H.; Latza, C.; Auler, M. M. K.; Grönke, S.; Partridge, L.; Annibal, A.

doi:10.1038/s41467-021-23856-9

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Regulation of the one carbon folate cycle as a shared metabolic signature of longevity

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Annibal, A.
Department Antebi - Molecular Genetics of Ageing, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons277998

Tharyan, R. G.
Department Antebi - Molecular Genetics of Ageing, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons278001

Schonewolff, M. F.
Department Antebi - Molecular Genetics of Ageing, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons278004

Tam, H.
Department Antebi - Molecular Genetics of Ageing, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons130926

Latza, C.
Department Antebi - Molecular Genetics of Ageing, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons278008

Auler, M. M. K.
Department Antebi - Molecular Genetics of Ageing, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons129428

Grönke, S.
Department Partridge - Biological Mechanisms of Ageing, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons129348

Partridge, L.
Department Partridge - Biological Mechanisms of Ageing, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons277995

Annibal, A.
Department Antebi - Molecular Genetics of Ageing, Max Planck Institute for Biology of Ageing, Max Planck Society;

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https://www.ncbi.nlm.nih.gov/pubmed/34108489
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Citation

Annibal, A., Tharyan, R. G., Schonewolff, M. F., Tam, H., Latza, C., Auler, M. M. K., et al. (2021). Regulation of the one carbon folate cycle as a shared metabolic signature of longevity. Nat Commun, 12(1), 3486. doi:10.1038/s41467-021-23856-9.

Cite as: https://hdl.handle.net/21.11116/0000-000A-F8C9-C

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.