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Increasing neuronal glucose uptake attenuates brain aging and promotes life span under dietary restriction in Drosophila
Brain 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 of Drosophila...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806808/ https://www.ncbi.nlm.nih.gov/pubmed/33490892 http://dx.doi.org/10.1016/j.isci.2020.101979 |
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author | Oka, Mikiko Suzuki, Emiko Asada, Akiko Saito, Taro Iijima, Koichi M. Ando, Kanae |
author_facet | Oka, Mikiko Suzuki, Emiko Asada, Akiko Saito, Taro Iijima, Koichi M. Ando, Kanae |
author_sort | Oka, Mikiko |
collection | PubMed |
description | Brain 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 of Drosophila during 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. |
format | Online Article Text |
id | pubmed-7806808 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-78068082021-01-22 Increasing neuronal glucose uptake attenuates brain aging and promotes life span under dietary restriction in Drosophila Oka, Mikiko Suzuki, Emiko Asada, Akiko Saito, Taro Iijima, Koichi M. Ando, Kanae iScience Article Brain 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 of Drosophila during 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. Elsevier 2021-01-05 /pmc/articles/PMC7806808/ /pubmed/33490892 http://dx.doi.org/10.1016/j.isci.2020.101979 Text en © 2020 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Oka, Mikiko Suzuki, Emiko Asada, Akiko Saito, Taro Iijima, Koichi M. Ando, Kanae Increasing neuronal glucose uptake attenuates brain aging and promotes life span under dietary restriction in Drosophila |
title | Increasing neuronal glucose uptake attenuates brain aging and promotes life span under dietary restriction in Drosophila |
title_full | Increasing neuronal glucose uptake attenuates brain aging and promotes life span under dietary restriction in Drosophila |
title_fullStr | Increasing neuronal glucose uptake attenuates brain aging and promotes life span under dietary restriction in Drosophila |
title_full_unstemmed | Increasing neuronal glucose uptake attenuates brain aging and promotes life span under dietary restriction in Drosophila |
title_short | Increasing neuronal glucose uptake attenuates brain aging and promotes life span under dietary restriction in Drosophila |
title_sort | increasing neuronal glucose uptake attenuates brain aging and promotes life span under dietary restriction in drosophila |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806808/ https://www.ncbi.nlm.nih.gov/pubmed/33490892 http://dx.doi.org/10.1016/j.isci.2020.101979 |
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