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.
journal_name
PLoS Genetjournal_title
PLoS geneticsauthors
Liu YJ,Janssens GE,McIntyre RL,Molenaars M,Kamble R,Gao AW,Jongejan A,Weeghel MV,MacInnes AW,Houtkooper RHdoi
10.1371/journal.pgen.1007633subject
Has Abstractpub_date
2019-03-07 00:00:00pages
e1007633issue
3eissn
1553-7390issn
1553-7404pii
PGENETICS-D-18-01607journal_volume
15pub_type
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