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了解衰老骨髓中的代谢变化。

Understanding metabolic changes in aging bone marrow.

作者信息

Connor Kwasi M, Hsu Young, Aggarwal Pardeep Kumar, Capone Stephen, Colombo Anthony R, Ramsingh Giridharan

机构信息

1Jane Anne Nohl Division of Hematology and Center for the Study of Blood Diseases, Keck School of Medicine of University of Southern California, 441 Eastlake Ave, MC 9172, Los Angeles, CA 90033 USA.

2Department of Biology, California Lutheran University, Thousand Oaks, CA 91360 USA.

出版信息

Exp Hematol Oncol. 2018 May 23;7:13. doi: 10.1186/s40164-018-0105-x. eCollection 2018.

DOI:10.1186/s40164-018-0105-x
PMID:29796337
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5966925/
Abstract

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.

摘要

背景

衰老与细胞水平上复杂的分子改变相关。随着衰老，骨髓会出现明显的表型、基因和表观遗传改变。与衰老相关的骨髓代谢变化尚未得到研究。

方法

在本研究中，我们对衰老小鼠骨髓的代谢组和转录组进行了表征，并将其与年轻健康小鼠和化疗处理小鼠的骨髓进行了比较；已知化疗会诱导造血过程中与年龄相关的变化。

结果

衰老骨髓的代谢组呈现出脂肪酸氧化受抑制的特征：游离脂肪酸积累、酰基肉碱减少以及β-羟基丁酸水平降低。衰老骨髓中的氨基酸和核酸池也显著减少。衰老骨髓的转录组揭示出氧化应激特征，已知其与线粒体功能障碍相关。最后，化疗处理小鼠骨髓的代谢和转录组谱未显示出广泛的与年龄相关的变化，而是大多类似于年轻健康小鼠，这表明化疗暴露不会导致“代谢衰老”。

结论

我们的结果揭示了衰老骨髓组织中脂质、氨基酸和核苷酸的广泛变化。这些数据共同为研究骨髓中与衰老相关的代谢变化提供了丰富的资源。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c1a/5966925/c7a31d529c41/40164_2018_105_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c1a/5966925/26e0acf78244/40164_2018_105_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c1a/5966925/bbbdc807c56b/40164_2018_105_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c1a/5966925/6ba173049bda/40164_2018_105_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c1a/5966925/04bcca6407a3/40164_2018_105_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c1a/5966925/c7a31d529c41/40164_2018_105_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c1a/5966925/26e0acf78244/40164_2018_105_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c1a/5966925/bbbdc807c56b/40164_2018_105_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c1a/5966925/6ba173049bda/40164_2018_105_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c1a/5966925/04bcca6407a3/40164_2018_105_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c1a/5966925/c7a31d529c41/40164_2018_105_Fig5_HTML.jpg

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