TY - JOUR
T1 - Transcriptomic profiles of aging in purified human immune cells
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
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
N1 - Publisher Copyright:
© 2015 Reynolds et al.; licensee BioMed Central.
PY - 2015/12/12
Y1 - 2015/12/12
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
UR - http://www.scopus.com/inward/record.url?scp=85014973164&partnerID=8YFLogxK
U2 - 10.1186/s12864-015-1522-4
DO - 10.1186/s12864-015-1522-4
M3 - Article
C2 - 25898983
AN - SCOPUS:85014973164
SN - 1471-2164
VL - 16
JO - BMC genomics
JF - BMC genomics
IS - 1
M1 - 333
ER -