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Understanding metabolic changes in aging bone marrow

BACKGROUND: Aging is associated with complex molecular alterations at the cellular level. Bone marrow exhibits distinct phenotypic, genetic and epigenetic alterations with aging. Metabolic changes in the bone marrow related to aging have not been studied. METHODS: In this study, we characterized the...

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Autores principales: Connor, Kwasi M., Hsu, Young, Aggarwal, Pardeep Kumar, Capone, Stephen, Colombo, Anthony R., Ramsingh, Giridharan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5966925/
https://www.ncbi.nlm.nih.gov/pubmed/29796337
http://dx.doi.org/10.1186/s40164-018-0105-x
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author Connor, Kwasi M.
Hsu, Young
Aggarwal, Pardeep Kumar
Capone, Stephen
Colombo, Anthony R.
Ramsingh, Giridharan
author_facet Connor, Kwasi M.
Hsu, Young
Aggarwal, Pardeep Kumar
Capone, Stephen
Colombo, Anthony R.
Ramsingh, Giridharan
author_sort Connor, Kwasi M.
collection PubMed
description BACKGROUND: Aging is associated with complex molecular alterations at the cellular level. Bone marrow exhibits distinct phenotypic, genetic and epigenetic alterations with aging. Metabolic changes in the bone marrow related to aging have not been studied. METHODS: In this study, we characterized the metabolome and transcriptome of aging murine bone marrow and compared it with bone marrow from young healthy mice and chemotherapy treated mice; chemotherapy treatment is known to induce age-related changes in hematopoiesis. RESULTS: The metabolome of the aging bone marrow exhibited a signature of suppressed fatty-acid oxidation: accumulation of free fatty acids, reduced acyl-carnitines and low β-hydroxy butyric acid. The aged bone marrow also exhibited a significant reduction in amino acid and nucleic acid pool. The transcriptome of the aging bone marrow revealed a signature of oxidative stress, known to be associated with mitochondrial dysfunction. Lastly, the metabolic and transcriptomic profiles of the bone marrow of chemotherapy treated mice did not show broad age-related changes but rather mostly resembled young healthy mice, suggestive of a lack of ‘metabolic aging’ with chemotherapy exposure. CONCLUSION: Our results revealed broad changes in lipids, amino acids, and nucleotides in aging marrow tissue. Together, these data provide a rich resource for the study of metabolic changes associated with aging in bone marrow. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40164-018-0105-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-59669252018-05-24 Understanding metabolic changes in aging bone marrow Connor, Kwasi M. Hsu, Young Aggarwal, Pardeep Kumar Capone, Stephen Colombo, Anthony R. Ramsingh, Giridharan Exp Hematol Oncol Research BACKGROUND: Aging is associated with complex molecular alterations at the cellular level. Bone marrow exhibits distinct phenotypic, genetic and epigenetic alterations with aging. Metabolic changes in the bone marrow related to aging have not been studied. METHODS: In this study, we characterized the metabolome and transcriptome of aging murine bone marrow and compared it with bone marrow from young healthy mice and chemotherapy treated mice; chemotherapy treatment is known to induce age-related changes in hematopoiesis. RESULTS: The metabolome of the aging bone marrow exhibited a signature of suppressed fatty-acid oxidation: accumulation of free fatty acids, reduced acyl-carnitines and low β-hydroxy butyric acid. The aged bone marrow also exhibited a significant reduction in amino acid and nucleic acid pool. The transcriptome of the aging bone marrow revealed a signature of oxidative stress, known to be associated with mitochondrial dysfunction. Lastly, the metabolic and transcriptomic profiles of the bone marrow of chemotherapy treated mice did not show broad age-related changes but rather mostly resembled young healthy mice, suggestive of a lack of ‘metabolic aging’ with chemotherapy exposure. CONCLUSION: Our results revealed broad changes in lipids, amino acids, and nucleotides in aging marrow tissue. Together, these data provide a rich resource for the study of metabolic changes associated with aging in bone marrow. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40164-018-0105-x) contains supplementary material, which is available to authorized users. BioMed Central 2018-05-23 /pmc/articles/PMC5966925/ /pubmed/29796337 http://dx.doi.org/10.1186/s40164-018-0105-x Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Connor, Kwasi M.
Hsu, Young
Aggarwal, Pardeep Kumar
Capone, Stephen
Colombo, Anthony R.
Ramsingh, Giridharan
Understanding metabolic changes in aging bone marrow
title Understanding metabolic changes in aging bone marrow
title_full Understanding metabolic changes in aging bone marrow
title_fullStr Understanding metabolic changes in aging bone marrow
title_full_unstemmed Understanding metabolic changes in aging bone marrow
title_short Understanding metabolic changes in aging bone marrow
title_sort understanding metabolic changes in aging bone marrow
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5966925/
https://www.ncbi.nlm.nih.gov/pubmed/29796337
http://dx.doi.org/10.1186/s40164-018-0105-x
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