Abstract
The natural polyphenol resveratrol stimulates sirtuins and extends lifespan. Here resveratrol inhibited expression of replicative senescence marker INK4a in human dermal fibroblasts, and 47 of 19,000 genes from microarray experiments were differentially expressed. These included genes for growth, cell division, cell signaling, apoptosis, and transcription. Genes involved in Ras and ubiquitin pathways, Ras-GRF1, RAC3, and UBE2D3, were downregulated. The changes suggest resveratrol might alter sirtuin-regulated downstream pathways, rather than sirtuin activity. Serum deprivation and high confluency caused nuclear translocation of the SIRT1-regulated transcription factor FOXO3a. Our data indicate resveratrol's actions might cause FOXO recruitment to the nucleus.
MeSH terms
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Aging / drug effects*
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Aging / genetics
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Aging / physiology*
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Cell Division / drug effects
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Cell Division / genetics
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Cell Line
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Cyclin-Dependent Kinase Inhibitor p16 / antagonists & inhibitors
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Cyclin-Dependent Kinase Inhibitor p16 / metabolism
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Fibroblasts / cytology*
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Fibroblasts / drug effects*
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Fibroblasts / metabolism
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Forkhead Box Protein O3
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Forkhead Transcription Factors / metabolism
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Gene Expression Profiling
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Humans
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Niacinamide / pharmacology
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Oligonucleotide Array Sequence Analysis
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Resveratrol
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Sirtuin 1
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Sirtuins / antagonists & inhibitors
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Sirtuins / physiology
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Stilbenes / metabolism
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Stilbenes / pharmacology*
Substances
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Cyclin-Dependent Kinase Inhibitor p16
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FOXO3 protein, human
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Forkhead Box Protein O3
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Forkhead Transcription Factors
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Stilbenes
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Niacinamide
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SIRT1 protein, human
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Sirtuin 1
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Sirtuins
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Resveratrol