Glycine promotes longevity in Caenorhabditis elegans in a methionine cycle-dependent fashion

PLoS Genet. 2019 Mar 7;15(3):e1007633. doi: 10.1371/journal.pgen.1007633. eCollection 2019 Mar.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / drug effects
  • Aging / genetics
  • Aging / metabolism
  • Animals
  • Caenorhabditis elegans / drug effects
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism*
  • Diet
  • Genes, Helminth
  • Glycine / administration & dosage
  • Glycine / metabolism*
  • Longevity / drug effects
  • Longevity / genetics
  • Longevity / physiology*
  • Metabolic Networks and Pathways / genetics
  • Methionine / metabolism*
  • Mutation
  • RNA Interference
  • Serine / administration & dosage
  • Serine / metabolism
  • Transcriptome / drug effects

Substances

  • Serine
  • Methionine
  • Glycine

Grants and funding

Work in the Houtkooper group is financially supported by an ERC Starting grant (no. 638290, https://erc.europa.eu/), and a VIDI grant from ZonMw (no. 91715305, https://www.zonmw.nl). AWM is supported by E-Rare-2, the ERA-Net for Research on Rare Diseases (ZonMW #40-44000-98-1008, www.erare.eu). GEJ is supported by a Federation of European Biochemical Society (FEBS, https://www.febs.org) long-term fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.