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

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.

ZIP-5/bZIP transcription factor regulation of folate metabolism is critical for aging axon regeneration

“…Unbiased bioinformatics analysis predicted that the human homologs of C. elegans ZIP-5 targets, including those regulating one-carbon metabolism, play a role in neurodegenerative diseases (Supplementary Table 5). In fact, one-carbon metabolism is upregulated in multiple longevity mutants 14 , and folic acid supplementation in wild-type animals increases lifespan 18 , suggesting a central role for folate metabolism in mediating longevity as well as repair. Our work suggests that dietary folate supplementation should be further developed as a novel approach to promote healthy brain aging, and also as a non-invasive treatment for patients with nerve trauma or neurodegenerative diseases associated with aging.…”

Mitochondrial translation and dynamics synergistically extend lifespan inC. elegansthrough HLH-30

“…no. c1389) that had been seeded with HT115 (DE3) bacteria transformed with either pL4440 empty vector or the indicated RNAi construct, as described before (Liu et al, 2019). At L4 larval stage, worms were transferred to 10 µM 5-fluorouracil (Sigma, cat.…”

“…Worms were subjected to RNAi bacteria upon hatching and grown at 20 °C until young adulthood, as described before (Liu et al, 2019). Approximately 500 synchronized worms were collected for total mRNA extraction at day 1 of adulthood.…”

Systematic Identification of Housekeeping Genes Possibly Used as References in Caenorhabditis elegans by Large-Scale Data Integration

“…Gene expression analysis in this model organism constitutes a powerful tool to discover new roles for different types of molecules. Traditionally, a set of housekeeping genes encoding actin (act-1) [7,8], tubulin (tba-1) [9][10][11], glyceraldehyde-3-phosphate dehydrogenase (gpd-2) [12,13], translation initiation factor 3C (eif-3.C) [14,15], calsequestrin (csq-1) [13,16], Rho GTPase (cdc-42) [17][18][19][20], and peroxisomal membrane protein related (pmp-3) [18,21] were thought to be appropriate reference genes for the normalization of gene expression in C. elegans. However, some reports indicated that the transcription levels of these conserved reference genes may be changed under different conditions, such as developmental stages, drug treatments, and hypoxia [22,23].…”