title: Cytomegalovirus (CMV)-dependent and -independent changes in the aging of the human immune system: a transcriptomic analysis.
abstract: Aging is associated with a profound reduction of the immune capacity (i.e., immunosenescence), which is manifested as increased morbidity and mortality due to infectious diseases in the elderly. The association of cytomegalovirus (CMV) with several aging-associated phenomena has been extensively characterized, e.g., the accumulation of CD8+ nonproliferative, apoptosis-resistant memory cells that have lost the expression of the costimulatory molecule CD28. However, as the CMV seroprevalence is notably high in elderly individuals, the role of CMV-independent changes has been difficult to analyze. To address this question, we performed a transcriptomic analysis (Illumina Human HT12 microarray) of the peripheral blood mononuclear cells (PBMCs) in a cohort of 90-year-old individuals (CMV seronegative, n=6; CMV seropositive, n=140) using the PBMCs of young CMV-seronegative individuals (n=11) as the controls. The cell type distribution (CD3, CD4, CD8, CD28 and CD14) was analyzed using FACS. The data showed that the gene expression profiles of the CMV+ and CMV- nonagenarians were different compared to the CMV- controls. Compared to the CMV- controls, 667 genes showed altered expression in the CMV- nonagenarians, and 559 genes were altered in the CMV+ nonagenarians. Of these, 337 genes were common. An analysis of the canonical pathways revealed that the number of affected pathways was also different (42 in CMV-, 13 in CMV+; of these, 9 were common). Taken together, these results indicate that the CMV-dependent and CMV-independent changes in the aging of the immune system are fundamentally different.
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, 33014 University of Tampere, Tampere, Finland. taru.kuparinen@uta.fi
authors.forename: Taru
authors.initials: T
authors.lastname: Kuparinen
authors.forename: Saara
authors.initials: S
authors.lastname: Marttila
authors.forename: Juulia
authors.initials: J
authors.lastname: Jylhävä
authors.forename: Liina
authors.initials: L
authors.lastname: Tserel
authors.forename: Pärt
authors.initials: P
authors.lastname: Peterson
authors.forename: Marja
authors.initials: M
authors.lastname: Jylhä
authors.forename: Antti
authors.initials: A
authors.lastname: Hervonen
authors.forename: Mikko
authors.initials: M
authors.lastname: Hurme
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics / Q000276:immunology*; D016022:Case-Control Studies; D003586:Cytomegalovirus Infections / Q000235:genetics / Q000276:immunology*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D055815:Young Adult