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Roforth et al. Genetic changes that come with age: Analyzing the genes involved



DOI:10.1038/bonekey.2016.6

Roforth et al. set out to find out more about how the aging process alters patterns of gene expression and DNA methylation within the bone marrow. They obtained and compared the mesenchymal cell population from young study participants who had a mean age of 28.7 (n=16) and an older population with a mean age of 73.3 (n=12).

The bone marrow mononuclear cells obtained from both groups were processed by cell sorting techniques to deliver a study population of lin−/CD34−/CD31− cells. These cells, which can differentiate into osteoblasts, have not previously been characterized. When freshly isolated cells were subjected to whole transcriptome RNA sequencing, 279 genes that were significantly differentially expressed between young and old subjects were identified.

Alterations in several signaling pathways were detected, including those for NFAT, calcium, gap junction, mTOR and melatonin. Significant differences were also noted in pathways important in protein synthesis and degradation. The promoters of 1528 genes that exhibited significant differences in gene expression by RNAseq, also showed differences in methylation when Reduced Representational Bisulphite DNA methylation sequencing was employed.

Editor’s comment: These studies provide novel insights into potential pathways affected by aging in a bone marrow aspirate. Findings of alterations in several genes and pathways leading to impaired protein synthesis and turnover with aging may help our understanding of age-related impairment in osteoblast function.


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