Transcriptome analysis of human ageing in male skin shows mid-life period of variability and central role of NF-κB

Scientific Reports - Tập 6 Số 1
Daniel Haustead1, Andrew Stevenson1, Vishal Saxena2, Fiona Marriage3, Martin J. Firth4, Robyn C Silla1, Lisa M. Martin1, Katharine F. Adcroft1, Suzanne Rea1, Philip J. Day3, Phillip E. Melton5, Fiona M. Wood4, Mark W. Fear1
1The Fiona Wood Foundation, Perth, 6000, WA, Australia
2Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, 02139, Massachusetts, USA
3Faculty of Medicine and Health Sciences, University of Manchester, M1 7DN, Manchester, UK
4Faculty of Medicine, Dentistry and Health Sciences, University of Western Australia, Crawley, 6009, WA, Australia
5Centre for Genetic Origins of Health and Disease, University of Western Australia, Crawley, 6009, WA, Australia

Tóm tắt

AbstractAge 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.

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