Journal
MECHANISMS OF AGEING AND DEVELOPMENT
Volume 133, Issue 7, Pages 498-507Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mad.2012.06.002
Keywords
Microarray; Gene expression; P16; Senescence; Skin fibroblasts; Stress
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Funding
- Innovation Oriented Research Program on Genomics (SenterNovem) [IGE01014, IGE5007]
- The Netherlands Genomics Initiative/Netherlands Organization for Scientific Research (NGI/NWO) [05040202, 050-060-810]
- Unilever PLC
- EU [FP6 036894]
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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 beta-gal activity. Microarray results identified gene sets involved in carbohydrate metabolism, Wnt/beta-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. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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