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Inositol polyphosphate multikinase (IPMK) is a conserved protein that initiates the production of inositol phosphate intracellular messengers and is critical for regulating a variety of cellular processes. Here, we report that the C. elegans IPMK-1, which is homologous to the mammalian inositol polyphosphate multikinase, plays a crucial role in regulating rhythmic behavior and development. The deletion mutant ipmk-1(tm2687) displays a long defecation cycle period and retarded postembryonic growth. The expression of functional ipmk-1::GFP was detected in the pharyngeal muscles, amphid sheath cells, the intestine, excretory (canal) cells, proximal gonad, and spermatheca. The expression of IPMK-1 in the intestine was sufficient for the wild-type phenotype. The IP3-kinase activity of IPMK-1 is required for defecation rhythms and postembryonic development. The defective phenotypes of ipmk-1(tm2687) could be rescued by a loss-of-function mutation in type I inositol 5-phosphatase homolog (IPP-5) and improved by a supplemental Ca 2+ in the medium. Our work demonstrates that IPMK-1 and the signaling molecule inositol triphosphate (IP3) pathway modulate rhythmic behaviors and development by dynamically regulating the concentration of intracellular Ca 2+ in C. elegans. Advances in understanding the molecular regulation of Ca 2+ homeostasis and regulation of organism development may lead to therapeutic strategies that modulate Ca 2+ signaling to enhance function and counteract disease processes. Unraveling the physiological role of IPMK and the underlying functional mechanism in C. elegans would contribute to understanding the role of IPMK in other species, especially in mammals, and benefit further research on the involvement of IPMK in disease., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Aging is related to the lowered overall functioning and increased risk for various age-related diseases in humans. Tectochrysin is a flavonoid compound and rich in a traditional Chinese Medicine Alpinia oxyphylla Miq., which has antioxidant, anti-inflammatory, anti-cancer, anti-bacterial, anti-diarrhea, hepatoprotective, and neuro-protective effects. Therefore, we tested if tectochrysin had an effect on aging in Caenorhabditis elegans (C. elegans). Our results showed that tectochrysin could extend the lifespan of C. elegans by up to 21.0%, delay the age-related decline of body movement, improve high temperature-stress resistance and anti-infection capacity, and protected worms against Aβ1-42-induced toxicity. Tectochrysin could not extend the lifespan of the mutants from genes daf-2, daf-16, eat-2, aak-2, skn-1, and hsf-1. Tectochrysin could increase the expression of DAF-16 regulated genes. The extension of lifespan by tectochrysin requires FOXO/DAF-16 and HSF-1. Overall, our findings suggest that tectochrysin may have a potential effect on extending lifespan and age-related diseases.

Aging is a complex life process, and a unified view is that metabolism plays key roles in all biological processes. Here, we determined the lipidomic profile of Caenorhabditis elegans ( C. elegans ) using ultraperformance liquid chromatography high-resolution mass spectrometry (UPLC-HRMS). Using a nontargeted approach, we detected approximately 3000 species. Analysis of the lipid metabolic profiles at young adult and ten-day-old ages among wild-type N2, glp-1 defective mutant, and double mutant daf-16;glp-1 uncovered significant age-related differences in the total amount of phosphatidylcholines (PC), sphingomyelins (SM), ceramides (Cer), diglycerides (DG), and triglycerides (TG). In addition, the age-associated lipid profiles were characterized by ratio of polyunsaturated (PUFA) over monounsaturated (MUFA) lipid species. Lipid metabolism modulation plays an important role in reproduction-regulated aging; to identify the variations of lipid metabolites during germ line loss-induced longevity, we investigated the lipidomic profiles of long-lived glp-1 /notch receptor mutants, which have reproductive deficiency when grown at nonpermissive temperature. The results showed that there was some age-related lipid variation, including TG 40:2, TG 40:1, and TG 41:1, which contributed to the long-life phenotype. The longevity of glp-1 mutant was daf-16 -dependent; the lipidome analysis of daf-16;glp-1 double mutant revealed that the changes of some metabolites in the glp-1 mutant were daf-16 -dependent, while other metabolites displayed more complex epistatic patterns. We first conducted a comprehensive lipidome analysis to provide novel insights into the relationships between longevity and lipid metabolism regulated by germ line signals in C. elegans .