Nicotinamide adenine dinucleotide extends the lifespan of Caenorhabditis elegans mediated by sir-2.1 and daf-16

Hashimoto, Teppei; Horikawa, Makoto; Nomura, Toshihisa; Sakamoto, Kazuichi

doi:10.1007/s10522-009-9225-3

Cited by 51 publications

(40 citation statements)

References 56 publications

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“…SIR proteins (collectively known as sirtuins) belong to a conserved family of nicotinamide adenine dinucleotide (NAD)-dependent deacetylases (class III NAD+-dependent deacetylase) implicated in the regulation of life span under calorie restriction. Their key role is in regulating glucose and lipid metabolism [135][136][137][138] . In mammals, there are seven homologs of SIR (SIRT1-7).…”

Section: Sirtuins Oxidative Stress and Mitochondrial Dysfunctionmentioning

confidence: 99%

“…The differential distribution of sirtuins implicates their distinct roles in cytosolic, mitochondrial, and nuclear events. SIRT1 is predominantly localized to the nuclear compartment and is implicated in regulating the transcriptional and epigenetic regulation of gene expression [135][136][137][138] . In contrast, SIRT2 is cytosolic, and SIRT3, SIRT4, and SIRT5 are mainly mitochondrial sirtuins [135][136][137][138] .…”

Section: Sirtuins Oxidative Stress and Mitochondrial Dysfunctionmentioning

confidence: 99%

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Mitochondria and Oxidative Stress in the Cardiorenal Metabolic Syndrome

et al. 2012

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Mitochondria play a fundamental role in the maintenance of normal structure, function, and survival of tissues. There is considerable evidence for mitochondrial dysfunction in association with metabolic diseases including insulin resistance, obesity, diabetes, and the cardiorenal metabolic syndrome. The phenomenon of reactive oxygen species (ROS)-induced ROS release through interactions between cytosolic and mitochondrial oxidative stress contributes to a vicious cycle of enhanced oxidative stress and mitochondrial dysfunction. Activation of the cytosolic and mitochondrial NADPH oxidase system, impairment of the mitochondrial electron transport, activation of p66shc pathway-targeting mitochondria, endoplasmic reticular stress, and activation of the mammalian target of the rapamycin-S6 kinase pathway underlie dysregulation of mitochondrial dynamics and promote mitochondrial oxidative stress. These processes are further modulated by acetyltransferases including sirtuin 1 and sirtuin 3, the former regulating nuclear acetylation and the latter regulating mitochondrial acetylation. The regulation of mitochondrial functions by microRNAs forms an additional layer of molecular control of mitochondrial oxidative stress. Alcohol further exacerbates mitochondrial oxidative stress induced by overnutrition and promotes the development of metabolic diseases.

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Section: Sirtuins Oxidative Stress and Mitochondrial Dysfunctionmentioning

confidence: 99%

Section: Sirtuins Oxidative Stress and Mitochondrial Dysfunctionmentioning

confidence: 99%

Mitochondria and Oxidative Stress in the Cardiorenal Metabolic Syndrome

et al. 2012

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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%

Age‐associated de‐repression of retrotransposons in the Drosophila fat body, its potential cause and consequence

et al. 2016

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SummaryEukaryotic genomes contain transposable elements (TE) that can move into new locations upon activation. Since uncontrolled transposition of TEs, including the retrotransposons and DNA transposons, can lead to DNA breaks and genomic instability, multiple mechanisms, including heterochromatin‐mediated repression, have evolved to repress TE activation. Studies in model organisms have shown that TEs become activated upon aging as a result of age‐associated deregulation of heterochromatin. Considering that different organisms or cell types may undergo distinct heterochromatin changes upon aging, it is important to identify pathways that lead to TE activation in specific tissues and cell types. Through deep sequencing of isolated RNAs, we report an increased expression of many retrotransposons in the old Drosophila fat body, an organ equivalent to the mammalian liver and adipose tissue. This de‐repression correlates with an increased number of DNA damage foci and decreased level of Drosophila lamin‐B in the old fat body cells. Depletion of the Drosophila lamin‐B in the young or larval fat body results in a reduction of heterochromatin and a corresponding increase in retrotransposon expression and DNA damage. Further manipulations of lamin‐B and retrotransposon expression suggest a role of the nuclear lamina in maintaining the genome integrity of the Drosophila fat body by repressing retrotransposons.

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“…In addition, accumulated data also show that the life-extending effects of CR are attributable to the increase of concentration of NAD ? , which then activates sirtuins (Lu and Lin 2010;Hashimoto et al 2010;Wood et al 2004). Our findings that 2-DG can extend lifespan of Hs68 cells in parallel with increased intracellular NAD ?…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have demonstrated that life extension of CR in organisms is mediated through the activation of Sirtuins (e.g., Sir2 in yeast and SIRT1 in human), possibly via sensing the increase of cellular NAD ? levels (Lu and Lin 2010;Kyrylenko and Baniahmad 2010;Hashimoto et al 2010;Ghosh 2008;Wood et al 2004). To date, it has become an interesting area for anti-aging research on CRM via the activation of sirtuins by pharmacological means (Ingram et al 2006;Chen and Guarente 2007;Aljada et al 2010).…”

Section: Introductionmentioning

confidence: 99%

Effects of 2-deoxyglucose and dehydroepiandrosterone on intracellular NAD+ level, SIRT1 activity and replicative lifespan of human Hs68 cells

et al. 2011

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2-Deoxy-D-glucose (2-DG) and dehydroepiandrosterone (DHEA) have been hypothesized to extend lifespan via mimicking calorie restriction (CR). Activation of sirtuins has been proposed to contribute to life extension of CR by increasing intercellular levels of NAD(+) in several organisms. However, it is unclear whether 2-DG and DHEA may affect intracellular NAD(+) levels and human sirtuin 1 (SIRT1) activities. Here, using human fibroblast Hs68 cells we showed that 2-DG increased intracellular NAD(+) levels in both time- and concentration-dependent manners. 2-DG also dose-dependently increased SIRT1 activities and the lifespan (measured as the cumulated growth curve of population doubling levels) of Hs68 cells. In contrast, DHEA at non-cytotoxic concentrations (≤50 μM) did not significantly affect NAD(+) levels, SIRT1 activities or the lifespan of Hs68 cells. These results suggest that 2-DG extends the lifespan of Hs68 cells by increased NAD(+) levels and SIRT1 activities, and that 2-DG has a potential as a CR mimetic.

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Nicotinamide adenine dinucleotide extends the lifespan of Caenorhabditis elegans mediated by sir-2.1 and daf-16

Cited by 51 publications

References 56 publications

Mitochondria and Oxidative Stress in the Cardiorenal Metabolic Syndrome

Mitochondria and Oxidative Stress in the Cardiorenal Metabolic Syndrome

Age‐associated de‐repression of retrotransposons in the Drosophila fat body, its potential cause and consequence

Effects of 2-deoxyglucose and dehydroepiandrosterone on intracellular NAD+ level, SIRT1 activity and replicative lifespan of human Hs68 cells

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