文章基本信息

标题：Increasing neuronal glucose uptake attenuates brain aging and promotes life span under dietary restriction in Drosophila
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作者：Mikiko Oka ; Emiko Suzuki ; Akiko Asada 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2021
卷号：24
期号：1
页码：1-24
DOI：10.1016/j.isci.2020.101979
语种：English
出版社：Elsevier
摘要：SummaryBrain neurons play a central role in organismal aging, but there is conflicting evidence about the role of neuronal glucose availability because glucose uptake and metabolism are associated with both aging and extended life span. Here, we analyzed metabolic changes in the brain neurons ofDrosophiladuring aging. Using a genetically encoded fluorescent adenosine triphosphate (ATP) biosensor, we found decreased ATP concentration in the neuronal somata of aged flies, correlated with decreased glucose content, expression of glucose transporter and glycolytic enzymes and mitochondrial quality. The age-associated reduction in ATP concentration did not occur in brain neurons with suppressed glycolysis or enhanced glucose uptake, suggesting these pathways contribute to ATP reductions. Despite age-associated mitochondrial damage, increasing glucose uptake maintained ATP levels, suppressed locomotor deficits, and extended the life span. Increasing neuronal glucose uptake during dietary restriction resulted in the longest life spans, suggesting an additive effect of enhancing glucose availability during a bioenergetic challenge on aging.Graphical AbstractDisplay OmittedFor a Figure360 author presentation of this figure, seehttps://doi.org/10.1016/j.isci.2020.101979Highlights•Imaging ofDrosophilabrain reveals aged neurons suffer from energy deficits•Increased neuronal glucose uptake attenuates age-dependent declines in ATP•Increased glucose uptake is beneficial despite age-dependent mitochondrial damage•Increased neuronal glucose uptake and dietary restriction further extend life spanBiological Sciences; Cellular Neuroscience; Endocrinology; Neuroscience; Physiology