TY - JOUR
T1 - Glycine promotes longevity in caenorhabditis elegans in a methionine cycle-dependent fashion
AU - Liu, Yasmine J.
AU - Janssens, Georges E.
AU - McIntyre, Rebecca L.
AU - Molenaars, Marte
AU - Kamble, Rashmi
AU - Gao, Arwen W.
AU - Jongejan, Aldo
AU - Van Weeghel, Michel
AU - Macinnes, Alyson W.
AU - Houtkooper, Riekelt H.
PY - 2019/3/1
Y1 - 2019/3/1
N2 - 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 serineand glycine-supplemented worms both demarked by wide-spread gene repression. Taken together, these data uncover a novel role of glycine in the deceleration of aging through its function in the methionine cycle. The authors thank the Caenorhabditis Genetics Center (CGC) at the University of Minnesota for providing C. elegans strains.
AB - 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 serineand glycine-supplemented worms both demarked by wide-spread gene repression. Taken together, these data uncover a novel role of glycine in the deceleration of aging through its function in the methionine cycle. The authors thank the Caenorhabditis Genetics Center (CGC) at the University of Minnesota for providing C. elegans strains.
KW - Aging/drug effects
KW - Animals
KW - Caenorhabditis elegans/drug effects
KW - Diet
KW - Genes, Helminth
KW - Glycine/administration & dosage
KW - Longevity/drug effects
KW - Metabolic Networks and Pathways/genetics
KW - Methionine/metabolism
KW - Mutation
KW - RNA Interference
KW - Serine/administration & dosage
KW - Transcriptome/drug effects
UR - http://www.scopus.com/inward/record.url?scp=85063302618&partnerID=8YFLogxK
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85063302618&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/30845140
U2 - https://doi.org/10.1371/journal.pgen.1007633
DO - https://doi.org/10.1371/journal.pgen.1007633
M3 - Article
C2 - 30845140
SN - 1553-7390
VL - 15
SP - e1007633
JO - PLoS genetics
JF - PLoS genetics
IS - 3
M1 - e1007633
ER -