Microarray-based identification of age-dependent differences in gene expression of human dermal fibroblasts

Pim Dekker, David Gunn, Tony McBryan, Roeland W. Dirks, Diana van Heemst, Fei Ling Lim, Aart G. Jochemsen, Matty Verlaan-de Vries, Julia Nagel, Peter D. Adams, Hans J. Tanke, Rudi G J Westendorp, Andrea B. Maier*

*Corresponding author for this work

    Research output: Contribution to JournalArticleAcademicpeer-review

    Abstract

    Senescence is thought to play an important role in the progressive age-related decline in tissue integrity and concomitant diseases, but not much is known about the complex interplay between upstream regulators and downstream effectors. We profiled whole genome gene expression of non-stressed and rotenone-stressed human fibroblast strains from young and oldest old subjects, and measured senescence associated β-gal activity. Microarray results identified gene sets involved in carbohydrate metabolism, Wnt/β-catenin signaling, the cell cycle, glutamate signaling, RNA-processing and mitochondrial function as being differentially regulated with chronological age. The most significantly differentially regulated mRNA corresponded to the p16 gene. p16 was then investigated using qPCR, Western blotting and immunocytochemistry. In conclusion, we have identified cellular pathways that are differentially expressed between fibroblast strains from young and old subjects.

    Original languageEnglish
    Pages (from-to)498-507
    Number of pages10
    JournalMechanisms of Ageing and Development
    Volume133
    Issue number7
    Early online date18 Jun 2012
    DOIs
    Publication statusPublished - Jul 2012

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    Keywords

    • Gene expression
    • Microarray
    • P16
    • Senescence
    • Skin fibroblasts
    • Stress

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