Glycine promotes longevity in Caenorhabditis elegans in a methionine cycle-dependent fashion.
Aging
/ drug effects
Animals
Caenorhabditis elegans
/ drug effects
Diet
Genes, Helminth
Glycine
/ administration & dosage
Longevity
/ drug effects
Metabolic Networks and Pathways
/ genetics
Methionine
/ metabolism
Mutation
RNA Interference
Serine
/ administration & dosage
Transcriptome
/ drug effects
Journal
PLoS genetics
ISSN: 1553-7404
Titre abrégé: PLoS Genet
Pays: United States
ID NLM: 101239074
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
10
08
2018
accepted:
06
02
2019
revised:
19
03
2019
pubmed:
8
3
2019
medline:
17
9
2019
entrez:
8
3
2019
Statut:
epublish
Résumé
The deregulation of metabolism is a hallmark of aging. As such, changes in the expression of metabolic genes and the profiles of amino acid levels are features associated with aging animals. We previously reported that the levels of most amino acids decline with age in Caenorhabditis elegans (C. elegans). Glycine, in contrast, substantially accumulates in aging C. elegans. In this study we show that this is coupled to a decrease in gene expression of enzymes important for glycine catabolism. We further show that supplementation of glycine significantly prolongs C. elegans lifespan, and early adulthood is important for its salutary effects. Moreover, supplementation of glycine ameliorates specific transcriptional changes that are associated with aging. Glycine feeds into the methionine cycle. We find that mutations in components of this cycle, methionine synthase (metr-1) and S-adenosylmethionine synthetase (sams-1), completely abrogate glycine-induced lifespan extension. Strikingly, the beneficial effects of glycine supplementation are conserved when we supplement with serine, which also feeds into the methionine cycle. RNA-sequencing reveals a similar transcriptional landscape in serine- and glycine-supplemented worms both demarked by widespread gene repression. Taken together, these data uncover a novel role of glycine in the deceleration of aging through its function in the methionine cycle.
Identifiants
pubmed: 30845140
doi: 10.1371/journal.pgen.1007633
pii: PGENETICS-D-18-01607
pmc: PMC6424468
doi:
Substances chimiques
Serine
452VLY9402
Methionine
AE28F7PNPL
Glycine
TE7660XO1C
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1007633Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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