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

Nature Communications
Andrea AnnibalAdam Antebi

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.

References

May 1, 1974·Genetics·S Brenner
Jul 21, 2001·Journal of Molecular Endocrinology·S Najib, V Sánchez-Margalet
Sep 11, 2002·The Journal of Nutrition·Dongmei SunAlison M Stephen
Oct 12, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Colin SelmanDominic J Withers
Dec 14, 2007·Proceedings of the National Academy of Sciences of the United States of America·Dana L Miller, Mark B Roth
May 6, 2009·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Liou SunJames M Harper
Feb 12, 2010·BMC Biology·Silke FuchsArmand M Leroi
Jun 24, 2011·Journal of the American College of Nutrition·Francesca PizzoloSimonetta Friso
Sep 21, 2011·Proceedings of the National Academy of Sciences of the United States of America·Hadise KabilScott D Pletcher
Mar 23, 2012·Nature Reviews. Molecular Cell Biology·Gary J PattiGary Siuzdak
May 31, 2012·Proceedings of the National Academy of Sciences of the United States of America·Lorenza E Moronetti MazzeoTodd Lamitina
Jul 24, 2012·Experimental Gerontology·Carmen E PerroneNorman Orentreich
Nov 24, 2012·Aging Cell·Jeffrey A ButlerShane L Rea
Jun 12, 2013·Cell·Carlos López-OtínGuido Kroemer
May 9, 2014·Nature·Jing FanJoshua D Rabinowitz
Aug 27, 2014·Biogerontology·Jennifer M A Tullet
Jan 17, 2015·Nature·Alejo EfeyanDavid M Sabatini
Dec 10, 2015·Nature Medicine·Toren Finkel
May 18, 2016·Journal of Biomolecular Structure & Dynamics·Anna AntosiewiczJoanna Cieśla
Jun 13, 2016·Trends in Endocrinology and Metabolism : TEM·George A Lemieux, Kaveh Ashrafi
Oct 30, 2016·Proceedings of the National Academy of Sciences of the United States of America·Takafumi OgawaMasaki Mizunuma
Jan 22, 2017·Experimental Gerontology·Gene P Ables, Jay E Johnson
May 4, 2017·Cell Metabolism·Bret H Goodpaster, Lauren M Sparks
Aug 31, 2017·Nature Communications·Varnesh TikuAdam Antebi
Oct 11, 2017·Journal of Cardiovascular Pharmacology·Desiree SmithYvo M Smulders
Nov 11, 2017·Science·Xin GuDavid M Sabatini

❮ Previous
Next ❯

Citations


❮ Previous
Next ❯

Software Mentioned

Compound discoverer
Excel
Trace finder
R ( Rstudio
GraphPad Prism
PIUMet
gplot

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Proceedings of the National Academy of Sciences of the United States of America
Wayne A Van Voorhies, S Ward
Free Radical Biology & Medicine
Natàlia Mota-MartorellReinald Pamplona
© 2021 Meta ULC. All rights reserved