2013
DOI: 10.18632/aging.100614
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Abstract: During aging, changes in chromatin state that alter gene transcription have been postulated to result in expression of genes that are normally silenced, leading to deleterious age-related effects on cellular physiology. Despite the prevalence of this hypothesis, it is primarily in yeast that loss of gene silencing with age has been well documented. We use a novel position effect variegation (PEV) reporter in Drosophila melanogaster to show that age-related loss of repressive heterochromatin is associated with … Show more

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Cited by 44 publications
(63 citation statements)
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References 27 publications
(63 reference statements)
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“…Importantly, overexpression of Sir2, a histone deacetylase required for heterochromatin formation and gene silencing, induces an increased lifespan in yeast (Kaeberlein et al ., 1999). The connection between heterochromatin maintenance and lifespan extension is further strengthened by studies in Caenorhabditis elegans and Drosophila (Rogina & Helfand, 2004; Hashimoto et al ., 2010; Jiang et al ., 2013; Whitaker et al ., 2013). Disruption of UTX‐1, a histone demethylase that reduces the heterochromatin epigenetic modification called histone H3 K27 trimethylation (H3K27me3), in C. elegans leads to increased H3K27me3 levels and prolonged lifespan (Jin et al ., 2011; Maures et al ., 2011).…”
Section: Introductionmentioning
confidence: 99%
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“…Importantly, overexpression of Sir2, a histone deacetylase required for heterochromatin formation and gene silencing, induces an increased lifespan in yeast (Kaeberlein et al ., 1999). The connection between heterochromatin maintenance and lifespan extension is further strengthened by studies in Caenorhabditis elegans and Drosophila (Rogina & Helfand, 2004; Hashimoto et al ., 2010; Jiang et al ., 2013; Whitaker et al ., 2013). Disruption of UTX‐1, a histone demethylase that reduces the heterochromatin epigenetic modification called histone H3 K27 trimethylation (H3K27me3), in C. elegans leads to increased H3K27me3 levels and prolonged lifespan (Jin et al ., 2011; Maures et al ., 2011).…”
Section: Introductionmentioning
confidence: 99%
“…Despite a clear connection between heterochromatin maintenance and lifespan extension (Feser et al ., 2010; Meister et al ., 2011; Larson et al ., 2012; Jiang et al ., 2013), the cause of heterochromatin loss and how it leads to cellular damage and aging is not well understood. Generally speaking, heterochromatin loss would lead to a mis‐expression of genes that are normally repressed, which could result in age‐ associated cellular defects.…”
Section: Introductionmentioning
confidence: 99%
“…In Caenorhabditis elegans, genetic manipulation of chromatin factors affecting histone methylation and acetylation directly affect life span (4). In Drosophila, the integrity of constitutive repressive heterochromatin declines with age at both the genomic and cellular level (5), with one consequence of these changes being an age-related loss of gene silencing in repressive constitutive heterochromatin regions in multiple tissues of the fly (6). In mice, changes in epigenetic chromatin marks are seen with age, and age-related phenotypes of behavior, memory, and learning are observed on genetic manipulation of certain histone marks (1).…”
mentioning
confidence: 99%
“…silencing in heterochromatin regions of yeast and flies through deacetylation of specific histone lysines required for establishment and spreading of heterochromatin (3,6,22). Increasing Sir2 expression has been shown to repress the normal age-related loss of gene silencing in heterochromatin regions in both yeast and flies (3,6), as well as the loss of gene silencing seen in mammalian embryonic stem cells undergoing genotoxic stress (23).…”
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confidence: 99%
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