title: Age gene expression and coexpression progressive signatures in peripheral blood leukocytes.
abstract: Both cellular senescence and organismic aging are known to be dynamic processes that start early in life and progress constantly during the whole life of the individual. In this work, with the objective of identifying signatures of age-related progressive change at the transcriptomic level, we have performed a whole-genome gene expression analysis of peripheral blood leukocytes in a group of healthy individuals with ages ranging from 14 to 93 years. A set of genes with progressively changing gene expression (either increase or decrease with age) has been identified and contextualized in a coexpression network. A modularity analysis has been performed on this network and biological-term and pathway enrichment analyses have been used for biological interpretation of each module. In summary, the results of the present work reveal the existence of a transcriptomic component that shows progressive expression changes associated to age in peripheral blood leukocytes, highlighting both the dynamic nature of the process and the need to complement young vs. elder studies with longitudinal studies that include middle aged individuals. From the transcriptional point of view, immunosenescence seems to be occurring from a relatively early age, at least from the late 20s/early 30s, and the 49-56 year old age-range appears to be critical. In general, the genes that, according to our results, show progressive expression changes with aging are involved in pathogenic/cellular processes that have classically been linked to aging in humans: cancer, immune processes and cellular growth vs. maintenance.
authors.affiliation: Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1498, New York, NY, USA; Multiple Sclerosis and Neuromuscular Diseases Groups, Neurosciences Area, Biodonostia Health Research Institute, Donostia/San Sebastián, Spain. Electronic address: haritz.irizar@biodonostia.org.
authors.forename: Haritz
authors.initials: H
authors.lastname: Irizar
authors.affiliation: Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, USA. Electronic address: goni.joaquin@gmail.com.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Goñi
authors.affiliation: Multiple Sclerosis and Neuromuscular Diseases Groups, Neurosciences Area, Biodonostia Health Research Institute, Donostia/San Sebastián, Spain. Electronic address: ainhoa.alzualde@gmail.com.
authors.forename: Ainhoa
authors.initials: A
authors.lastname: Alzualde
authors.affiliation: Multiple Sclerosis and Neuromuscular Diseases Groups, Neurosciences Area, Biodonostia Health Research Institute, Donostia/San Sebastián, Spain; Neurology Department, Donostia University Hospital, Donostia/San Sebastián, Spain. Electronic address: tamara.castillotrivino@osakidetza.eus.
authors.forename: Tamara
authors.initials: T
authors.lastname: Castillo-Triviño
authors.affiliation: Multiple Sclerosis and Neuromuscular Diseases Groups, Neurosciences Area, Biodonostia Health Research Institute, Donostia/San Sebastián, Spain; Neurology Department, Donostia University Hospital, Donostia/San Sebastián, Spain. Electronic address: olascoaga.javier@gmail.com.
authors.forename: Javier
authors.initials: J
authors.lastname: Olascoaga
authors.affiliation: Multiple Sclerosis and Neuromuscular Diseases Groups, Neurosciences Area, Biodonostia Health Research Institute, Donostia/San Sebastián, Spain; Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, USA; Neurology Department, Donostia University Hospital, Donostia/San Sebastián, Spain; Department of Neuroscience, University of the Basque Country (UPV/EHU), Leioa, Spain; Centro Investigación Biomédica en Red Enfermedades Neurodegenerativas (CIBERNED), Spain. Electronic address: adolfojose.lopezdemunainarregui@osakidetza.eus.
authors.forename: Adolfo
authors.initials: A
authors.lastname: Lopez de Munain
authors.affiliation: Multiple Sclerosis and Neuromuscular Diseases Groups, Neurosciences Area, Biodonostia Health Research Institute, Donostia/San Sebastián, Spain; Neurology Department, Donostia University Hospital, Donostia/San Sebastián, Spain. Electronic address: david.otaegui@biodonostia.org.
authors.forename: David
authors.initials: D
authors.lastname: Otaegui
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D016922:Cellular Senescence / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D064368:Healthy Volunteers; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000235:genetics*; D055815:Young Adult
keywords: Aging; Coexpression; Peripheral blood; Progressive change; Transcriptomics