A sensitive mass spectrometry platform identifies metabolic changes of life history traits in C. elegans

Abstract

Abnormal nutrient metabolism is a hallmark of aging, and the underlying genetic and nutritional framework is rapidly being uncovered, particularly using C. elegans as a model. However, the direct metabolic consequences of perturbations in life history of C. elegans remain to be clarified. Based on recent advances in the metabolomics field, we optimized and validated a sensitive mass spectrometry (MS) platform for identification of major metabolite classes in worms and applied it to study age and diet related changes. Using this platform that allowed detection of over 600 metabolites in a sample of 2500 worms, we observed marked changes in fatty acids, amino acids and phospholipids during worm life history, which were independent from the germ-line. Worms underwent a striking shift in lipid metabolism after early adulthood that was at least partly controlled by the metabolic regulator AAK-2/AMPK. Most amino acids peaked during development, except aspartic acid and glycine, which accumulated in aged worms. Dietary intervention also influenced worm metabolite profiles and the regulation was highly specific depending on the metabolite class. Altogether, these MS-based methods are powerful tools to perform worm metabolomics for aging and metabolism-oriented studies.

Dietary Restriction and AMPK Increase Lifespan via Mitochondrial Network and Peroxisome Remodeling

“…Interestingly, a recent study in C. elegans that examined the effect of age on metabolite profiles reported that FA levels in wild-type and aak-2 null mutants are very similar at day 1. However, there is an increase in wild-type FA levels at day 7 that is blunted in aak-2 mutants (Gao et al, 2017), which led us to hypothesize that activating AMPK might increase lifespan via a shift to FAO as animals age. In support of a causal role for FAO, treatment with PHX has no effect on wild-type animals but reduces lifespan extension by 50% in CA-AAK-2 animals (Figures 7C and 7D; Table S1).…”

Glycine promotes longevity inCaenorhabditis elegansin a methionine cycle-dependent fashion

“…We reported that the concentrations of most amino acids peak at the later larval stage or early adult phase and then began declining at different adult stages, reaching low levels by the latest stages of the animals' life (21). One stark exception was glycine, which continued to accumulate in aged worms (21).…”

“…We previously measured amino acid levels throughout the life of C. elegans, including four larval phases (L1-L4) and ten days of adulthood from young worms to aged ones (days 1-10) (21). We reported that the concentrations of most amino acids peak at the later larval stage or early adult phase and then began declining at different adult stages, reaching low levels by the latest stages of the animals' life (21). One stark exception was glycine, which continued to accumulate in aged worms (21).…”

“…We recently showed that glycine accumulates with age in a large scale metabolomics study profiling levels of fatty acids, amino acids, and phospholipids across the lifespan of C. elegans, (21). Another study in human fibroblast suggested that the epigenetic suppression of two nuclear-coded genes, glycine C-acetyltransferase (GCAT) and serine hydroxymethyltransferase 2 (SHMT2), which are involved in glycine synthesis in mitochondria, was partly responsible for aging-associated mitochondrial respiration defects and that glycine treatment rejuvenated the respiration capacity of fibroblasts derived from elderly individuals (22).…”

In vitro and in vivo defensive effect of probiotic LAB against Pseudomonas aeruginosa using Caenorhabditis elegans model

“…The longevity of C. elegans was measured using a previously described method by Smolentsevae et al [32]. In the experiment, 50 μL of the target bacterial strain cultured in TS and MRS broth at 25°C for 24 h was spread on a 35 mm diameter NGM agar plate and incubated overnight at 37°C.…”