Abstract
In Caenorhabditis elegans (C. elegans), ablation of germline stem cells (GSCs) leads to infertility, which extends lifespan. It has been reported that aging and reproduction are both inextricably associated with metabolism. However, few studies have investigated the roles of polar small molecules metabolism in regulating longevity by reproduction. In this work, we combined the nuclear magnetic resonance (NMR) and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) to profile the water-soluble metabolome in C. elegans. Comparing the metabolic fingerprint between two physiological ages among different mutants, our results demonstrate that aging is characterized by metabolome remodeling and metabolic decline. In addition, by analyzing the metabolic profiles of long-lived germline-less glp-1 mutants, we discovered that glp-1 mutants regulate the levels of many age-variant metabolites to attenuate aging, including elevated concentrations of the pyrimidine and purine metabolism intermediates and decreased concentrations of the citric acid cycle intermediates. Interestingly, by analyzing the metabolome of daf-16;glp-1 double mutants, our results revealed that some metabolic exchange contributing to germline-mediated longevity was mediated by transcription factor FOXO/DAF-16, including pyrimidine metabolism and the TCA cycle. Based on a comprehensive metabolic analysis, we provide novel insight into the relationship between longevity and metabolism regulated by germline signals in C. elegans
Highlights
Aging is an inevitable and complex part of life and has been a fascinating phenomenon for several thousands of years
To characterize the metabolic changes that occur during aging in C. elegans, we acquired 1H nuclear magnetic resonance (NMR) metabolic profiles of wild-type N2 in young adults (YA) and day 10 adults (10A) and analyzed the data using two multivariate statistical methods: unsupervised principal component analysis (PCA) [30] and supervised OPLS-DA [31] models (Figure 1A and Figure 6A)
Our results showed that, compared with YA N2, the concentrations of alanine, cystathionine, isoleucine, leucine, lysine, phenylalanine, glycine, valine, 3aminoisobutyric acid, and succinate were decreased in the 10A N2 worms, while those of GPC, phosphorylcholine, aspartate and trehalose were increased (Figure 1A)
Summary
Aging is an inevitable and complex part of life and has been a fascinating phenomenon for several thousands of years. Reproductive capacity is closely related to aging, and previous studies have demonstrated the apparent trade-off between reproduction and aging Consistent with this idea, longevity can be achieved by sacrificing fertile potential in many species, including Caenorhabditis elegans (C. elegans) [1, 2], drosophila melanogaster [3], and humans [4], suggesting that the relationship between reproduction and aging is conserved. Reproduction is an energetically costly process, and it has been reported that reduced reproduction is associated with elevated fat storage and prolonged lifespans in multiple organisms [5, 6]. These findings seem to indicate that the longevity of a species is a direct result how it distributes its resources between reproduction and survival. In the nematode C. elegans, laser ablation of germline stem cells (GSCs) precursors or genetic ablation of GLP-1/Notch signaling causes GSC proliferation to be inhibited, which can activate signals in somatic tissues that significantly lengthen lifespan [1] and alter lipid metabolism [7], known as the www.aging‐us.com
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
