title: Transcriptome analysis of human ageing in male skin shows mid-life period of variability and central role of NF-κB.
abstract: Age is well-known to be a significant factor in both disease pathology and response to treatment, yet the molecular changes that occur with age in humans remain ill-defined. Here, using transcriptome profiling of healthy human male skin, we demonstrate that there is a period of significantly elevated, transcriptome-wide expression changes occurring predominantly in middle age. Both pre and post this period, the transcriptome appears to undergo much smaller, linear changes with increasing age. Functional analysis of the transient changes in middle age suggest a period of heightened metabolic activity and cellular damage associated with NF-kappa-B and TNF signaling pathways. Through meta-analysis we also show the presence of global, tissue independent linear transcriptome changes with age which appear to be regulated by NF-kappa-B. These results suggest that aging in human skin is associated with a critical mid-life period with widespread transcriptome changes, both preceded and proceeded by a relatively steady rate of linear change in the transcriptome. The data provides insight into molecular changes associated with normal aging and will help to better understand the increasingly important pathological changes associated with aging.
authors.affiliation: The Fiona Wood Foundation, Perth, WA 6000, Australia.|Faculty of Medicine, Dentistry and Health Sciences, University of Western Australia, Crawley WA 6009, Australia.|Faculty of Medicine and Health Sciences, University of Manchester, Manchester, M1 7DN, UK.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Haustead
authors.affiliation: The Fiona Wood Foundation, Perth, WA 6000, Australia.|Burn Injury Research Unit, School of Surgery, University of Western Australia, Crawley WA 6009, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Stevenson
authors.affiliation: Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Vishal
authors.initials: V
authors.lastname: Saxena
authors.affiliation: Faculty of Medicine and Health Sciences, University of Manchester, Manchester, M1 7DN, UK.
authors.forename: Fiona
authors.initials: F
authors.lastname: Marriage
authors.affiliation: Faculty of Medicine, Dentistry and Health Sciences, University of Western Australia, Crawley WA 6009, Australia.
authors.forename: Martin
authors.initials: M
authors.lastname: Firth
authors.affiliation: The Fiona Wood Foundation, Perth, WA 6000, Australia.|Burns Service of Western Australia, Royal Perth Hospital and Princess Margaret Hospital, WA 6000, Australia.
authors.forename: Robyn
authors.initials: R
authors.lastname: Silla
authors.affiliation: The Fiona Wood Foundation, Perth, WA 6000, Australia.|Burns Service of Western Australia, Royal Perth Hospital and Princess Margaret Hospital, WA 6000, Australia.
authors.forename: Lisa
authors.initials: L
authors.lastname: Martin
authors.affiliation: The Fiona Wood Foundation, Perth, WA 6000, Australia.|Burn Injury Research Unit, School of Surgery, University of Western Australia, Crawley WA 6009, Australia.
authors.forename: Katharine F
authors.initials: KF
authors.lastname: Adcroft
authors.affiliation: The Fiona Wood Foundation, Perth, WA 6000, Australia.|Burn Injury Research Unit, School of Surgery, University of Western Australia, Crawley WA 6009, Australia.|Burns Service of Western Australia, Royal Perth Hospital and Princess Margaret Hospital, WA 6000, Australia.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Rea
authors.affiliation: Faculty of Medicine and Health Sciences, University of Manchester, Manchester, M1 7DN, UK.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Day
authors.affiliation: Centre for Genetic Origins of Health and Disease, University of Western Australia, Crawley WA , Australia 6009.
authors.forename: Phillip
authors.initials: P
authors.lastname: Melton
authors.affiliation: The Fiona Wood Foundation, Perth, WA 6000, Australia.|Faculty of Medicine, Dentistry and Health Sciences, University of Western Australia, Crawley WA 6009, Australia.|Burn Injury Research Unit, School of Surgery, University of Western Australia, Crawley WA 6009, Australia.|Burns Service of Western Australia, Royal Perth Hospital and Princess Margaret Hospital, WA 6000, Australia.
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Wood
authors.affiliation: The Fiona Wood Foundation, Perth, WA 6000, Australia.|Burn Injury Research Unit, School of Surgery, University of Western Australia, Crawley WA 6009, Australia.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Fear
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D012867:Skin / Q000378:metabolism*; D013312:Stress, Physiological; D059467:Transcriptome; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016328:NF-kappa B; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha