ABSTRACT
Abstract@#The study elaborates on the historical development of the home-school-community partnership in the United States, as well as physical activity strategies to prevent overweight and obesity in school age children. Feasible suggestions are proposed for implementing the home-school-community collaboration in China. The finding suggests that in addition to cooperation with schools, families and communities need to take initiatives to actively support children s participation in various physical activities and provide facilities and guarantees. Schools should also do a top level design that links with families and communities, and incorporate their participation into long term physical education planning, making them an integral part of a closely interconnected collaborative network to further prevent overweight and obesity in school age children.
ABSTRACT
In Alzheimer's disease, ion permeability through the ionic channel formed by Aß peptides on cellular membranes appears to underlie neuronal cell death. An understanding of the formation mechanism of the toxic ionic channel by Aß peptides is very important, but remains unclear. Our simulation results demonstrated the dynamics and mechanism of channel formation by Aß1-28 peptides on the DPPC and POPC membrane by the coarse-grained method. The ionic channel formation is driven by the gyration of the radius and solvent accessible molecular surface area of Aß1-28 peptides. The ionic channel formation mechanism was explored by the free energy profile based on the distribution of the gyration of the radius and solvent accessible molecular surface area of Aß1-28 peptides on the fluid membrane. The stability and water permeability of the ionic channel formed by Aß peptides was investigated by all-atomic model simulation. Our simulation showed that the ionic channel formed by Aß1-28 peptides is very stable and has a good water permeability. This could help us to understand the pore formation mechanism by Aß1-28 peptides on the fluidic membrane. It also provides us with a guideline by which to understand the toxicity of Aß1-28 peptides' pores to the cell.
Subject(s)
Alzheimer Disease , Amyloid beta-Peptides , Alzheimer Disease/metabolism , Amyloid beta-Peptides/metabolism , Humans , Ion Channels/metabolism , Molecular Dynamics Simulation , Peptide Fragments/chemistry , Solvents , Water/metabolismABSTRACT
The contents of numerous membrane lipids change upon ageing. However, it is unknown whether and how any of these changes are causally linked to lifespan regulation. Acyl chains contribute to the functional specificity of membrane lipids. In this study, working with C. elegans, we identified an acyl chain-specific sphingolipid, C22 glucosylceramide, as a longevity metabolite. Germline deficiency, a conserved lifespan-extending paradigm, induces somatic expression of the fatty acid elongase ELO-3, and behenic acid (22:0) generated by ELO-3 is incorporated into glucosylceramide for lifespan regulation. Mechanistically, C22 glucosylceramide is required for the membrane localization of clathrin, a protein that regulates membrane budding. The reduction in C22 glucosylceramide impairs the clathrin-dependent autophagic lysosome reformation, which subsequently leads to TOR activation and longevity suppression. These findings reveal a mechanistic link between membrane lipids and ageing and suggest a model of lifespan regulation by fatty acid-mediated membrane configuration.
Subject(s)
Caenorhabditis elegans/physiology , Fatty Acids, Nonesterified/metabolism , Glycosphingolipids/metabolism , Homeostasis , Longevity/physiology , Lysosomes/metabolism , Animals , Caenorhabditis elegans Proteins/metabolism , Ceramides/metabolism , Cholesterol/metabolism , Clathrin/metabolism , Germ-Line Mutation/genetics , Green Fluorescent Proteins/metabolism , Larva/metabolism , Models, Biological , RNA Interference , Stress, PhysiologicalABSTRACT
The transcription factor SKN-1, the C. elegans ortholog of mammalian Nrf protein, is a well-known longevity factor, and its activation is observed in several long-lived models. SKN-1 also plays essential roles in xenobiotic and oxidative stress responses. Here, we report deleterious functions of SKN-1 in somatic stress resistance that may impair lifespan. Constitutive SKN-1 activation impairs animal resistance to several stresses, including heat, ER stress and mitochondrial stress, which result from the suppression of DAF-16, another master regulator of longevity. SKN-1 activation abrogates DAF-16 nuclear import and downregulates DAF-16 target genes under stress conditions, while SKN-1 inhibition promotes the expression of DAF-16 targets, even in long-lived mutants. Further, SKN-1 activation induces the expression of vitellogenin proteins, which are required for SKN-1-mediated suppression of DAF-16 and stress resistance. Together, these findings identify detrimental roles for SKN-1 activation in animal health, and more importantly, inspire the rethinking of the complex roles for SKN-1 in aging regulation.
