Unlocking Aging Astrocyte Metabolic Switch | Aging-US



October 23, 2023

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  • Aging-US published this research paper on April 18, 2023 in Volume 15, Issue 19, entitled, “Metabolic switch in the aging astrocyte supported via integrative approach comprising network and transcriptome analyses" by researchers from Instituto de Nutrición y Tecnología de Alimentos (INTA), Universidad de Chile, Santiago, Región Metropolitana 7800003, Chile; Department of Physics, Universidad de Chile, Santiago, Región Metropolitana 7800003, Chile; Center for the Development of Nanoscience and Nanotechnology, CEDENNA, Santiago, Región Metropolitana 7800003, Chile; Department of Physics, Center for Advanced Nanoscience, University of California, San Diego, CA; Centro de Estudios Científicos (CECs), Valdivia 5110466, Chile; Facultad de Medicina y Ciencia, Universidad San Sebastián, Valdivia, Región de Los Ríos 5110773, Chile; Department of Biology, Laboratory of Cellular and Neuronal Dynamics, Faculty of Sciences, Universidad de Chile, Santiago, Región Metropolitana 7800003, Chile; Geroscience Center for Brain Health and Metabolism (GERO), Santiago, Región Metropolitana 7800003, Chile; Facultad de Medicina y Ciencia, Universidad San Sebastián, Santiago, Región Metropolitana 7510157, Chile; The Buck Institute for Research on Aging, Novato, CA. DOI - https://doi.org/10.18632/aging.204663 Corresponding authors - Christian González-Billault - chrgonza@uchile.cl, and Dasfne Lee-Liu - dasfne.lee@uss.cl Abstract Dysregulated central-energy metabolism is a hallmark of brain aging. Supplying enough energy for neurotransmission relies on the neuron-astrocyte metabolic network. To identify genes contributing to age-associated brain functional decline, we formulated an approach to analyze the metabolic network by integrating flux, network structure and transcriptomic databases of neurotransmission and aging. Our findings support that during brain aging: (1) The astrocyte undergoes a metabolic switch from aerobic glycolysis to oxidative phosphorylation, decreasing lactate supply to the neuron, while the neuron suffers intrinsic energetic deficit by downregulation of Krebs cycle genes, including mdh1 and mdh2 (Malate-Aspartate Shuttle); (2) Branched-chain amino acid degradation genes were downregulated, identifying dld as a central regulator; (3) Ketone body synthesis increases in the neuron, while the astrocyte increases their utilization, in line with neuronal energy deficit in favor of astrocytes. We identified candidates for preclinical studies targeting energy metabolism to prevent age-associated cognitive decline. Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204663 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, astrocyte, neuron, brain aging, flux balance analysis, network centrality About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM


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