Transcriptomic profiles of aging in purified human immune cells

Lindsay M. Reynolds, Jingzhong Ding, Jackson R. Taylor, Kurt Lohman, Nicola Soranzo, Alberto de la Fuente, Tie Fu Liu, Craig Johnson, R. Graham Barr, Thomas C. Register, Kathleen M. Donohue, Monica V. Talor, Daniela Cihakova, Charles Gu, Jasmin Divers, David Siscovick, Gregory Burke, Wendy S Post, Steven Shea, David R. JacobsIna Hoeschele, Charles E. McCall, Stephen B. Kritchevsky, David Herrington, Russell P. Tracy, Yongmei Liu

Research output: Contribution to journalArticle

Abstract

Background: Transcriptomic studies hold great potential towards understanding the human aging process. Previous transcriptomic studies have identified many genes with age-associated expression levels; however, small samples sizes and mixed cell types often make these results difficult to interpret. Results: Using transcriptomic profiles in CD14+ monocytes from 1,264 participants of the Multi-Ethnic Study of Atherosclerosis (aged 55-94 years), we identified 2,704 genes differentially expressed with chronological age (false discovery rate, FDR = 0.001). We further identified six networks of co-expressed genes that included prominent genes from three pathways: protein synthesis (particularly mitochondrial ribosomal genes), oxidative phosphorylation, and autophagy, with expression patterns suggesting these pathways decline with age. Expression of several chromatin remodeler and transcriptional modifier genes strongly correlated with expression of oxidative phosphorylation and ribosomal protein synthesis genes. 17% of genes with age-associated expression harbored CpG sites whose degree of methylation significantly mediated the relationship between age and gene expression (p <0.05). Lastly, 15 genes with age-associated expression were also associated (FDR = 0.01) with pulse pressure independent of chronological age. Comparing transcriptomic profiles of CD14+ monocytes to CD4+ T cells from a subset (n = 423) of the population, we identified 30 age-associated (FDR <0.01) genes in common, while larger sets of differentially expressed genes were unique to either T cells (188 genes) or monocytes (383 genes). At the pathway level, a decline in ribosomal protein synthesis machinery gene expression with age was detectable in both cell types. Conclusions: An overall decline in expression of ribosomal protein synthesis genes with age was detected in CD14+ monocytes and CD4+ T cells, demonstrating that some patterns of aging are likely shared between different cell types. Our findings also support cell-specific effects of age on gene expression, illustrating the importance of using purified cell samples for future transcriptomic studies. Longitudinal work is required to establish the relationship between identified age-associated genes/pathways and aging-related diseases.

Original languageEnglish (US)
Article number333
JournalBMC Genomics
Volume16
Issue number1
DOIs
StatePublished - Apr 22 2015

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Genes
Monocytes
Protein Biosynthesis
Oxidative Phosphorylation
Gene Expression
Modifier Genes
T-Lymphocytes
Mitochondrial Genes
Autophagy
T-Lymphocyte Subsets
Sample Size
Methylation
Chromatin
Atherosclerosis
Blood Pressure
Population
Proteins

Keywords

  • Aging
  • Autophagy
  • Methylation
  • Mitochondrial ribosome
  • Monocyte
  • Oxidative phosphorylation
  • Protein synthesis
  • Ribonucleoprotein complex
  • T cell
  • Transcriptome
  • Translation

ASJC Scopus subject areas

  • Biotechnology
  • Genetics

Cite this

Reynolds, L. M., Ding, J., Taylor, J. R., Lohman, K., Soranzo, N., de la Fuente, A., ... Liu, Y. (2015). Transcriptomic profiles of aging in purified human immune cells. BMC Genomics, 16(1), [333]. https://doi.org/10.1186/s12864-015-1522-4

Transcriptomic profiles of aging in purified human immune cells. / Reynolds, Lindsay M.; Ding, Jingzhong; Taylor, Jackson R.; Lohman, Kurt; Soranzo, Nicola; de la Fuente, Alberto; Liu, Tie Fu; Johnson, Craig; Barr, R. Graham; Register, Thomas C.; Donohue, Kathleen M.; Talor, Monica V.; Cihakova, Daniela; Gu, Charles; Divers, Jasmin; Siscovick, David; Burke, Gregory; Post, Wendy S; Shea, Steven; Jacobs, David R.; Hoeschele, Ina; McCall, Charles E.; Kritchevsky, Stephen B.; Herrington, David; Tracy, Russell P.; Liu, Yongmei.

In: BMC Genomics, Vol. 16, No. 1, 333, 22.04.2015.

Research output: Contribution to journalArticle

Reynolds, LM, Ding, J, Taylor, JR, Lohman, K, Soranzo, N, de la Fuente, A, Liu, TF, Johnson, C, Barr, RG, Register, TC, Donohue, KM, Talor, MV, Cihakova, D, Gu, C, Divers, J, Siscovick, D, Burke, G, Post, WS, Shea, S, Jacobs, DR, Hoeschele, I, McCall, CE, Kritchevsky, SB, Herrington, D, Tracy, RP & Liu, Y 2015, 'Transcriptomic profiles of aging in purified human immune cells', BMC Genomics, vol. 16, no. 1, 333. https://doi.org/10.1186/s12864-015-1522-4
Reynolds LM, Ding J, Taylor JR, Lohman K, Soranzo N, de la Fuente A et al. Transcriptomic profiles of aging in purified human immune cells. BMC Genomics. 2015 Apr 22;16(1). 333. https://doi.org/10.1186/s12864-015-1522-4
Reynolds, Lindsay M. ; Ding, Jingzhong ; Taylor, Jackson R. ; Lohman, Kurt ; Soranzo, Nicola ; de la Fuente, Alberto ; Liu, Tie Fu ; Johnson, Craig ; Barr, R. Graham ; Register, Thomas C. ; Donohue, Kathleen M. ; Talor, Monica V. ; Cihakova, Daniela ; Gu, Charles ; Divers, Jasmin ; Siscovick, David ; Burke, Gregory ; Post, Wendy S ; Shea, Steven ; Jacobs, David R. ; Hoeschele, Ina ; McCall, Charles E. ; Kritchevsky, Stephen B. ; Herrington, David ; Tracy, Russell P. ; Liu, Yongmei. / Transcriptomic profiles of aging in purified human immune cells. In: BMC Genomics. 2015 ; Vol. 16, No. 1.
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AU - Reynolds, Lindsay M.

AU - Ding, Jingzhong

AU - Taylor, Jackson R.

AU - Lohman, Kurt

AU - Soranzo, Nicola

AU - de la Fuente, Alberto

AU - Liu, Tie Fu

AU - Johnson, Craig

AU - Barr, R. Graham

AU - Register, Thomas C.

AU - Donohue, Kathleen M.

AU - Talor, Monica V.

AU - Cihakova, Daniela

AU - Gu, Charles

AU - Divers, Jasmin

AU - Siscovick, David

AU - Burke, Gregory

AU - Post, Wendy S

AU - Shea, Steven

AU - Jacobs, David R.

AU - Hoeschele, Ina

AU - McCall, Charles E.

AU - Kritchevsky, Stephen B.

AU - Herrington, David

AU - Tracy, Russell P.

AU - Liu, Yongmei

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N2 - Background: Transcriptomic studies hold great potential towards understanding the human aging process. Previous transcriptomic studies have identified many genes with age-associated expression levels; however, small samples sizes and mixed cell types often make these results difficult to interpret. Results: Using transcriptomic profiles in CD14+ monocytes from 1,264 participants of the Multi-Ethnic Study of Atherosclerosis (aged 55-94 years), we identified 2,704 genes differentially expressed with chronological age (false discovery rate, FDR = 0.001). We further identified six networks of co-expressed genes that included prominent genes from three pathways: protein synthesis (particularly mitochondrial ribosomal genes), oxidative phosphorylation, and autophagy, with expression patterns suggesting these pathways decline with age. Expression of several chromatin remodeler and transcriptional modifier genes strongly correlated with expression of oxidative phosphorylation and ribosomal protein synthesis genes. 17% of genes with age-associated expression harbored CpG sites whose degree of methylation significantly mediated the relationship between age and gene expression (p <0.05). Lastly, 15 genes with age-associated expression were also associated (FDR = 0.01) with pulse pressure independent of chronological age. Comparing transcriptomic profiles of CD14+ monocytes to CD4+ T cells from a subset (n = 423) of the population, we identified 30 age-associated (FDR <0.01) genes in common, while larger sets of differentially expressed genes were unique to either T cells (188 genes) or monocytes (383 genes). At the pathway level, a decline in ribosomal protein synthesis machinery gene expression with age was detectable in both cell types. Conclusions: An overall decline in expression of ribosomal protein synthesis genes with age was detected in CD14+ monocytes and CD4+ T cells, demonstrating that some patterns of aging are likely shared between different cell types. Our findings also support cell-specific effects of age on gene expression, illustrating the importance of using purified cell samples for future transcriptomic studies. Longitudinal work is required to establish the relationship between identified age-associated genes/pathways and aging-related diseases.

AB - Background: Transcriptomic studies hold great potential towards understanding the human aging process. Previous transcriptomic studies have identified many genes with age-associated expression levels; however, small samples sizes and mixed cell types often make these results difficult to interpret. Results: Using transcriptomic profiles in CD14+ monocytes from 1,264 participants of the Multi-Ethnic Study of Atherosclerosis (aged 55-94 years), we identified 2,704 genes differentially expressed with chronological age (false discovery rate, FDR = 0.001). We further identified six networks of co-expressed genes that included prominent genes from three pathways: protein synthesis (particularly mitochondrial ribosomal genes), oxidative phosphorylation, and autophagy, with expression patterns suggesting these pathways decline with age. Expression of several chromatin remodeler and transcriptional modifier genes strongly correlated with expression of oxidative phosphorylation and ribosomal protein synthesis genes. 17% of genes with age-associated expression harbored CpG sites whose degree of methylation significantly mediated the relationship between age and gene expression (p <0.05). Lastly, 15 genes with age-associated expression were also associated (FDR = 0.01) with pulse pressure independent of chronological age. Comparing transcriptomic profiles of CD14+ monocytes to CD4+ T cells from a subset (n = 423) of the population, we identified 30 age-associated (FDR <0.01) genes in common, while larger sets of differentially expressed genes were unique to either T cells (188 genes) or monocytes (383 genes). At the pathway level, a decline in ribosomal protein synthesis machinery gene expression with age was detectable in both cell types. Conclusions: An overall decline in expression of ribosomal protein synthesis genes with age was detected in CD14+ monocytes and CD4+ T cells, demonstrating that some patterns of aging are likely shared between different cell types. Our findings also support cell-specific effects of age on gene expression, illustrating the importance of using purified cell samples for future transcriptomic studies. Longitudinal work is required to establish the relationship between identified age-associated genes/pathways and aging-related diseases.

KW - Aging

KW - Autophagy

KW - Methylation

KW - Mitochondrial ribosome

KW - Monocyte

KW - Oxidative phosphorylation

KW - Protein synthesis

KW - Ribonucleoprotein complex

KW - T cell

KW - Transcriptome

KW - Translation

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