title: Transcriptomic profiles of aging in purified human immune cells.
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.
authors.affiliation: Department of Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, 27157, USA. lireynol@wakehealth.edu.
authors.forename: Lindsay M
authors.initials: LM
authors.lastname: Reynolds
authors.affiliation: Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, 27157, USA. jding@wakehealth.edu.
authors.forename: Jingzhong
authors.initials: J
authors.lastname: Ding
authors.affiliation: Department of Gerontology and Geriatric Medicine, J. Paul Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, North Carolina, 27157, USA. jtaylor@wakehealth.edu.
authors.forename: Jackson R
authors.initials: JR
authors.lastname: Taylor
authors.affiliation: Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, 27157, USA. klohman@wakehealth.edu.
authors.forename: Kurt
authors.initials: K
authors.lastname: Lohman
authors.affiliation: CRS4 Bioinformatica, Pula, 09010, Italy. soranzo@crs4.it.
authors.forename: Nicola
authors.initials: N
authors.lastname: Soranzo
authors.affiliation: FBN, Leibniz Institute for Farm Animal Biology, Genetics and Biometry, Mecklenburg-Vorpommern, Germany. alf@fbn-dummerstorf.de.
authors.forename: Alberto
authors.initials: A
authors.lastname: de la Fuente
authors.affiliation: Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, 27157, USA. tliu@wakehealth.edu.
authors.forename: Tie Fu
authors.initials: TF
authors.lastname: Liu
authors.affiliation: Departments of Medicine and Epidemiology, Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, 98115, USA. wcraigj@u.washington.edu.
authors.forename: Craig
authors.initials: C
authors.lastname: Johnson
authors.affiliation: Departments of Medicine and Epidemiology, Columbia University, New York, New York, 10032, USA. rgb9@columbia.edu.
authors.forename: R Graham
authors.initials: RG
authors.lastname: Barr
authors.affiliation: Department of Pathology, Wake Forest School of Medicine, Winston-Salem, North Carolina, 27157, USA. register@wakehealth.edu.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Register
authors.affiliation: Departments of Medicine and Epidemiology, Columbia University, New York, New York, 10032, USA. kd2128@columbia.edu.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Donohue
authors.affiliation: Department of Pathology, Johns Hopkins University, Baltimore, Maryland, 21205, USA. mtalor@jhmi.edu.
authors.forename: Monica V
authors.initials: MV
authors.lastname: Talor
authors.affiliation: Department of Pathology, Johns Hopkins University, Baltimore, Maryland, 21205, USA. dcihako1@jhmi.edu.
authors.forename: Daniela
authors.initials: D
authors.lastname: Cihakova
authors.affiliation: Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri, 63110, USA. gc@wubios.wustl.edu.
authors.forename: Charles
authors.initials: C
authors.lastname: Gu
authors.affiliation: Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, 27157, USA. jdivers@wakehealth.edu.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Divers
authors.affiliation: New York Academy of Medicine, New York, New York, 10029, USA. dsiscovick@nyam.org.
authors.forename: David
authors.initials: D
authors.lastname: Siscovick
authors.affiliation: Department of Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, 27157, USA. gburke@wfubmc.edu.
authors.forename: Gregory
authors.initials: G
authors.lastname: Burke
authors.affiliation: Department of Pathology, Johns Hopkins University, Baltimore, Maryland, 21205, USA. wpost@jhmi.edu.
authors.forename: Wendy
authors.initials: W
authors.lastname: Post
authors.affiliation: Departments of Medicine and Epidemiology, Columbia University, New York, New York, 10032, USA. ss35@columbia.edu.
authors.forename: Steven
authors.initials: S
authors.lastname: Shea
authors.affiliation: Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, 55454, USA. jacob004@umn.edu.
authors.forename: David R
authors.initials: DR
authors.lastname: Jacobs
authors.affiliation: Virginia Bioinformatics Institute, Virginia Tech, Blacksburg, Virginia, 24061, USA. inah@vbi.vt.edu.
authors.forename: Ina
authors.initials: I
authors.lastname: Hoeschele
authors.affiliation: Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, 27157, USA. chmccall@wfubmc.edu.|Department of Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, 27157, USA. chmccall@wfubmc.edu.
authors.forename: Charles E
authors.initials: CE
authors.lastname: McCall
authors.affiliation: Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, 27157, USA. skritche@wakehealth.edu.|Department of Gerontology and Geriatric Medicine, J. Paul Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, North Carolina, 27157, USA. skritche@wakehealth.edu.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Kritchevsky
authors.affiliation: Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, 27157, USA. dherring@wakehealth.edu.
authors.forename: David
authors.initials: D
authors.lastname: Herrington
authors.affiliation: Department of Pathology, University of Vermont, Colchester, Vermont, 05446, USA. russell.tracy@uvm.edu.
authors.forename: Russell P
authors.initials: RP
authors.lastname: Tracy
authors.affiliation: Department of Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, 27157, USA. yoliu@wakehealth.edu.
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D001343:Autophagy / Q000235:genetics; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D005260:Female; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D014176:Protein Biosynthesis / Q000235:genetics; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D059467:Transcriptome
chemical_list: D018950:Lipopolysaccharide Receptors