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Accumulation of Long-Chain Glycosphingolipids during Aging Is Prevented by Caloric Restriction

BACKGROUND: Chronic kidney disease and end-stage renal disease are major causes of morbidity and mortality that are seen far more commonly in the aged population. Interestingly, kidney function declines during aging even in the absence of underlying renal disease. Declining renal function has been a...

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Autores principales: Hernández-Corbacho, María José, Jenkins, Russell W., Clarke, Christopher J., Hannun, Yusuf A., Obeid, Lina M., Snider, Ashley J., Siskind, Leah J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3110726/
https://www.ncbi.nlm.nih.gov/pubmed/21687659
http://dx.doi.org/10.1371/journal.pone.0020411
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author Hernández-Corbacho, María José
Jenkins, Russell W.
Clarke, Christopher J.
Hannun, Yusuf A.
Obeid, Lina M.
Snider, Ashley J.
Siskind, Leah J.
author_facet Hernández-Corbacho, María José
Jenkins, Russell W.
Clarke, Christopher J.
Hannun, Yusuf A.
Obeid, Lina M.
Snider, Ashley J.
Siskind, Leah J.
author_sort Hernández-Corbacho, María José
collection PubMed
description BACKGROUND: Chronic kidney disease and end-stage renal disease are major causes of morbidity and mortality that are seen far more commonly in the aged population. Interestingly, kidney function declines during aging even in the absence of underlying renal disease. Declining renal function has been associated with age-related cellular damage and dysfunction with reports of increased levels of apoptosis, necrosis, and inflammation in the aged kidney. Bioactive sphingolipids have been shown to regulate these same cellular processes, and have also been suggested to play a role in aging and cellular senescence. METHODOLOGY/PRINCIPAL FINDINGS: We hypothesized that alterations in kidney sphingolipids play a role in the declining kidney function that occurs during aging. To begin to address this, the sphingolipid profile was measured in young (3 mo), middle aged (9 mo) and old (17 mo) C57BL/6 male mice. Interestingly, while modest changes in ceramides and sphingoid bases were evident in kidneys from older mice, the most dramatic elevations were seen in long-chain hexosylceramides (HexCer) and lactosylceramides (LacCer), with C14- and C16-lactosylceramides elevated as much as 8 and 12-fold, respectively. Increases in long-chain LacCers during aging are not exclusive to the kidney, as they also occur in the liver and brain. Importantly, caloric restriction, previously shown to prevent the declining kidney function seen in aging, inhibits accumulation of long-chain HexCer/LacCers and prevents the age-associated elevation of enzymes involved in their synthesis. Additionally, long-chain LacCers are also significantly elevated in human fibroblasts isolated from elderly individuals. CONCLUSION/SIGNIFICANCE: This study demonstrates accumulation of the glycosphingolipids HexCer and LacCer in several different organs in rodents and humans during aging. In addition, data demonstrate that HexCer and LacCer metabolism is regulated by caloric restriction. Taken together, data suggest that HexCer/LacCers are important mediators of cellular processes fundamental to mammalian aging.
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spelling pubmed-31107262011-06-16 Accumulation of Long-Chain Glycosphingolipids during Aging Is Prevented by Caloric Restriction Hernández-Corbacho, María José Jenkins, Russell W. Clarke, Christopher J. Hannun, Yusuf A. Obeid, Lina M. Snider, Ashley J. Siskind, Leah J. PLoS One Research Article BACKGROUND: Chronic kidney disease and end-stage renal disease are major causes of morbidity and mortality that are seen far more commonly in the aged population. Interestingly, kidney function declines during aging even in the absence of underlying renal disease. Declining renal function has been associated with age-related cellular damage and dysfunction with reports of increased levels of apoptosis, necrosis, and inflammation in the aged kidney. Bioactive sphingolipids have been shown to regulate these same cellular processes, and have also been suggested to play a role in aging and cellular senescence. METHODOLOGY/PRINCIPAL FINDINGS: We hypothesized that alterations in kidney sphingolipids play a role in the declining kidney function that occurs during aging. To begin to address this, the sphingolipid profile was measured in young (3 mo), middle aged (9 mo) and old (17 mo) C57BL/6 male mice. Interestingly, while modest changes in ceramides and sphingoid bases were evident in kidneys from older mice, the most dramatic elevations were seen in long-chain hexosylceramides (HexCer) and lactosylceramides (LacCer), with C14- and C16-lactosylceramides elevated as much as 8 and 12-fold, respectively. Increases in long-chain LacCers during aging are not exclusive to the kidney, as they also occur in the liver and brain. Importantly, caloric restriction, previously shown to prevent the declining kidney function seen in aging, inhibits accumulation of long-chain HexCer/LacCers and prevents the age-associated elevation of enzymes involved in their synthesis. Additionally, long-chain LacCers are also significantly elevated in human fibroblasts isolated from elderly individuals. CONCLUSION/SIGNIFICANCE: This study demonstrates accumulation of the glycosphingolipids HexCer and LacCer in several different organs in rodents and humans during aging. In addition, data demonstrate that HexCer and LacCer metabolism is regulated by caloric restriction. Taken together, data suggest that HexCer/LacCers are important mediators of cellular processes fundamental to mammalian aging. Public Library of Science 2011-06-08 /pmc/articles/PMC3110726/ /pubmed/21687659 http://dx.doi.org/10.1371/journal.pone.0020411 Text en This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
spellingShingle Research Article
Hernández-Corbacho, María José
Jenkins, Russell W.
Clarke, Christopher J.
Hannun, Yusuf A.
Obeid, Lina M.
Snider, Ashley J.
Siskind, Leah J.
Accumulation of Long-Chain Glycosphingolipids during Aging Is Prevented by Caloric Restriction
title Accumulation of Long-Chain Glycosphingolipids during Aging Is Prevented by Caloric Restriction
title_full Accumulation of Long-Chain Glycosphingolipids during Aging Is Prevented by Caloric Restriction
title_fullStr Accumulation of Long-Chain Glycosphingolipids during Aging Is Prevented by Caloric Restriction
title_full_unstemmed Accumulation of Long-Chain Glycosphingolipids during Aging Is Prevented by Caloric Restriction
title_short Accumulation of Long-Chain Glycosphingolipids during Aging Is Prevented by Caloric Restriction
title_sort accumulation of long-chain glycosphingolipids during aging is prevented by caloric restriction
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3110726/
https://www.ncbi.nlm.nih.gov/pubmed/21687659
http://dx.doi.org/10.1371/journal.pone.0020411
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