Integrative Analysis Reveals Metabolic Switch in Aging Astrocytes
10-24-2023“We identified candidates for preclinical studies targeting energy metabolism to prevent age-associated cognitive decline.”
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BUFFALO, NY- October 24, 2023 – A new research paper was published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 15, Issue 19, entitled, “Metabolic switch in the aging astrocyte supported via integrative approach comprising network and transcriptome analyses.”
Dysregulated central-energy metabolism is a hallmark of brain aging. Supplying enough energy for neurotransmission relies on the neuron-astrocyte metabolic network. In their new study, researchers Alejandro Acevedo, Felipe Torres, Miguel Kiwi, Felipe Baeza-Lehnert, L. Felipe Barros, Dasfne Lee-Liu, and Christian González-Billault from Universidad de Chile, Cedenna, University of California, San Diego, Centro de Estudios Científicos (CECs), Geroscience Center for Brain Health and Metabolism (GERO), Universidad San Sebastián, and the Buck Institute for Research on Aging aimed 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.”
Their 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.
“The genes identified here are valuable candidates for future studies to understand the molecular mechanisms of healthy brain aging and prevent brain age-associated failure using energy metabolism as a target.”
Read the full paper: DOI: https://doi.org/10.18632/aging.204663
Corresponding Authors: Christian González-Billault, Dasfne Lee-Liu
Corresponding Emails: chrgonza@uchile.cl, dasfne.lee@uss.cl
Keywords: astrocyte, neuron, brain aging, flux balance analysis, network centrality
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About Aging-US:
Aging publishes research papers in all fields of aging research including but not limited, aging from yeast to mammals, cellular senescence, age-related diseases such as cancer and Alzheimer’s diseases and their prevention and treatment, anti-aging strategies and drug development and especially the role of signal transduction pathways such as mTOR in aging and potential approaches to modulate these signaling pathways to extend lifespan. The journal aims to promote treatment of age-related diseases by slowing down aging, validation of anti-aging drugs by treating age-related diseases, prevention of cancer by inhibiting aging. Cancer and COVID-19 are age-related diseases.
Aging is indexed by PubMed/Medline (abbreviated as “Aging (Albany NY)”), PubMed Central, Web of Science: Science Citation Index Expanded (abbreviated as “Aging‐US” and listed in the Cell Biology and Geriatrics & Gerontology categories), Scopus (abbreviated as “Aging” and listed in the Cell Biology and Aging categories), Biological Abstracts, BIOSIS Previews, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).
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