Rpd3 interacts with insulin signaling in Drosophila longevity extension

Woods, Jared K.; Ziafazeli, Tahereh; Rogina, Blanka

doi:10.18632/aging.101110

Cited by 10 publications

(11 citation statements)

References 46 publications

(60 reference statements)

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“…We have reported that rpd3 reduction increases resistance to hydrogen peroxide, but this resistance depends on fly age and sex. Resistance is higher in females compared to males, and more pronounced at older ages [ 18 ]. Increased resistance to paraquat is also observed in flies with heart-specific rpd3 reduction, as well as whole body reduction in 2 days old flies [ 15 ].…”

Section: Resultsmentioning

confidence: 99%

The effects of reduced rpd3 levels on fly physiology

Woods

Ziafazeli

Rogina

2017

NHA

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BACKGROUND: Rpd3 is a conserved histone deacetylase that removes acetyl groups from lysine residues within histones and other proteins. Reduction or inhibition of Rpd3 extends longevity in yeast, worms, and flies. Previous studies in flies suggest an overlap with the mechanism of lifespan extension by dietary restriction. However, the mechanism of rpd3’s effects on longevity remains unclear.OBJECTIVES: In this study we investigated how rpd3 reduction affects fly spontaneous physical activity, fecundity, and stress resistance.METHODS: We examined the effects of rpd3 reduction on fly spontaneous physical activity by using population monitors, we determined female fecundity by counting daily egg laying, and we determined fly survivorship in response to starvation and paraquat.RESULTS: In flies, rpd3 reduction increases peak spontaneous physical activity of rpd3def male flies at a young age but does not affect total 24 hour activity. Male and female rpd3def mutants are more resistant to starvation on low and high calorie diets. In addition, increased resistance to paraquat was observed in females of one allele. A decrease in rpd3 levels does not affect female fecundity.CONCLUSIONS: A decrease in rpd3 levels mirrors some but not all changes associated with calorie restriction, illustrated by an increased peak of spontaneous activity in rpd3def/+ heterozygous male flies but no effect on total spontaneous activity and fecundity.

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Section: Resultsmentioning

confidence: 99%

The effects of reduced rpd3 levels on fly physiology

Woods

Ziafazeli

Rogina

2017

NHA

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“…This reduced catabolism is related to the dietary restriction (DR) that extends lifespan in several species [39]. Also, it was recently reported that Rpd3 interacts partially with the insulin signaling pathway of the DR longevity mechanism [8,45].…”

Section: Discussionmentioning

confidence: 99%

“…However, systemic downregulation of Rpd3 extends lifespan [5,6], which is also observed in yeast with reduced Rpd3 expression [7]. Recently, it has been reported that Rpd3 interacts partially with the insulin signaling longevity pathway [8]. As several long-lived mutant flies display increased resistance to numerous stressors including oxidation, starvation, and heat compared to wild-type flies [9-12], Rpd3 downregulation also enhances stress resistance with extended lifespan [6].…”

Section: Introductionmentioning

confidence: 99%

Longer lifespan in the Rpd3 and Loco signaling results from the reduced catabolism in young age with noncoding RNA

Kopp

Park

2019

Aging

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Downregulation of Rpd3 (histone deacetylase) or Loco (regulator of G-protein signaling protein) extends Drosophila lifespan with higher stress resistance. We found rpd3-downregulated long-lived flies genetically interact with loco-upregulated short-lived flies in stress resistance and lifespan. Gene expression profiles between those flies revealed that they regulate common target genes in metabolic enzymes and signaling pathways, showing an opposite expression pattern in their contrasting lifespans. Functional analyses of more significantly changed genes indicated that the activities of catabolic enzymes and uptake/storage proteins are reduced in long-lived flies with Rpd3 downregulation. This reduced catabolism exhibited from a young age is considered to be necessary for the resultant longer lifespan of the Rpd3- and Loco-downregulated old flies, which mimics the dietary restriction (DR) effect that extends lifespan in the several species. Inversely, those catabolic activities that break down carbohydrates, lipids, and peptides were high in the short lifespan of Loco-upregulated flies. Long noncoding gene, dntRL (CR45923), was also found as a putative target modulated by Rpd3 and Loco for the longevity. Interestingly, this dntRL could affect stress resistance and lifespan, suggesting that the dntRL lncRNA may be involved in the metabolic mechanism of Rpd3 and Loco signaling.

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“…Rpd3 is a zinc-dependent histone deacetylase in Drosophila and a homolog of mammal HDAC1. Reduction or inhibition of rpd3 extends longevity, increases energy storage and downregulates gene expressions of the IIS pathway [72]. There is an overlap between rpd3 and IIS longevity pathways, as mutations in rpd3 and dfoxo showed weakened stress resistance compared with rpd3 single mutant flies [72].…”

Section: Histone Modifications In Invertebrate Agingmentioning

confidence: 99%

“…Reduction or inhibition of rpd3 extends longevity, increases energy storage and downregulates gene expressions of the IIS pathway [72]. There is an overlap between rpd3 and IIS longevity pathways, as mutations in rpd3 and dfoxo showed weakened stress resistance compared with rpd3 single mutant flies [72]. Lifespan extension in rpd3 mutant flies may overlap with the mechanism of extension seen in dietary restriction (DR).…”

Section: Histone Modifications In Invertebrate Agingmentioning

confidence: 99%

The Epigenetics of Aging in Invertebrates

Gao

et al. 2019

IJMS

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Aging is an unstoppable process coupled to the loss of physiological function and increased susceptibility to diseases. Epigenetic alteration is one of the hallmarks of aging, which involves changes in DNA methylation patterns, post-translational modification of histones, chromatin remodeling and non-coding RNA interference. Invertebrate model organisms, such as Drosophila melanogaster and Caenorhabditis elegans, have been used to investigate the biological mechanisms of aging because they show, evolutionarily, the conservation of many aspects of aging. In this review, we focus on recent advances in the epigenetic changes of aging with invertebrate models, providing insight into the relationship between epigenetic dynamics and aging. conserved in both insects and mammals, where it regulates the rate of aging [11]. Therefore, this review will summarize recent advances in the roles of epigenetic changes in aging in these two invertebrates. DNA Methylation in Invertebrate AgingDNA methylation is a covalent chemical modification, which usually occurs at 5-methyl cytosine (5mC) and which is enriched in cytosine phosphate guanine (CpG) dinucleotides [12]. CpG methylation within promoters leads to transcriptional repression through the formation of compact chromatin structures such as heterochromatin. Conversely, promoters of genes that are highly expressed are devoid of DNA methylation, hence their name-CpG islands [13]. The dynamic changes in DNA methylation can impact aging and health. The local methylation level increases while the global methylation level decreases with aging [14]. Age-related DNA methylation changes are also correlated with human age-related diseases, such as cancer and sarcopenia [15,16]. Cytosine methylation is catalyzed by three DNA methyltransferases (DNMTs): DNMT1, DNMT3a, and DNMT3b. Three ten-eleven translocation (TET) proteins initiate the specific demethylation of 5mC residues in DNA: TET1, TET2, and TET3 [17]. The schematic diagram of DNA methylation and demethylation is shown in Figure 1. Worms do not encode a conventional DNA methyltransferase to silence DNA repeats, which led to the prevailing view that DNA methylation does not occur in C. elegans [18]. Similarly, in adult D. melanogaster, only a low level of DNA methylation was confirmed [19,20]. In Drosophila, overexpression of the DNA methyltransferase gene, dDnmt2, extends lifespan in a small heat shock protein-dependent way [21]. However, although 5mC methylation is rare, methylation on N6 adenine (6mA) is prevalent in C. elegans and D. melanogaster [22,23]. Recent studies have confirmed that NMAD-1 (MT-A70 family) and DMAD (DNA 6mA demethylase, TET ortholog) are 6mA demethylases in C. elegans and D. melanogaster, respectively. DAMT-1 (AlKB family) is likely a 6mA methyltransferase in C. elegans [24]. NMAD-1 and DAMT-1 can regulate 6mA levels and control the epigenetic inheritance of phenotypes associated with the loss of the H3K4me2 demethylase spr-5 [22]. The worm mutant of spr-5 displayed a transgenerational increase in H3K4me...

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Rpd3 interacts with insulin signaling in Drosophila longevity extension

Cited by 10 publications

References 46 publications

The effects of reduced rpd3 levels on fly physiology

The effects of reduced rpd3 levels on fly physiology

Longer lifespan in the Rpd3 and Loco signaling results from the reduced catabolism in young age with noncoding RNA

The Epigenetics of Aging in Invertebrates

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