Increased mitochondrial biogenesis preserves intestinal stem cell homeostasis and contributes to longevity in Indy mutant flies

Rogers, Ryan Patricia; Rogina, Blanka

doi:10.18632/aging.100658

Cited by 32 publications

(64 citation statements)

References 36 publications

(87 reference statements)

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“…Additionally, specific rpd3 downregulation in fly heart tissue extends fly longevity and increases fly resistance to oxidation, starvation, and heat (Kopp et al, 2015). Consistently, increased resistance to stress is associated with longer life in many other long-lived flies, such as mth and Indy mutants (Lin et al, 1998; Rogers and Rogina, 2014). …”

Section: Effects Of Rpd3 On Longevitymentioning

confidence: 78%

The effects of Rpd3 on fly metabolism, health, and longevity

Woods

Rogina

2016

Experimental Gerontology

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The epigenetic regulation of DNA structure and function is essential for changes in gene expression involved in development, growth, and maintenance of cellular function. Epigenetic changes include histone modifications such as methylation, acetylation, ubiquitination, and phosphorylation. Histone deacetylase (HDAC) proteins have a major role in epigenetic regulation of chromatin structure. HDACs are enzymes that catalyze the removal of acetyl groups from lysine residues within histones, as well as a range of other proteins including transcriptional factors. HDACs are highly conserved proteins divided into two families and based on sequence similarity in four classes. Here we will discuss the roles of Rpd3 in physiology and longevity with emphasis on its role in flies. Rpd3, the Drosophila HDAC1 homologue, is a class I lysine deacetylase and a member of a large family of HDAC proteins. Rpd3 has multiple functions including control of proliferation, development, metabolism, and aging. Pharmacological and dietary HDAC inhibitors have been used as therapeutics in psychiatry, cancer, and neurology.

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Section: Effects Of Rpd3 On Longevitymentioning

confidence: 78%

The effects of Rpd3 on fly metabolism, health, and longevity

Woods

Rogina

2016

Experimental Gerontology

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“…For protein, BioRad protein solution was diluted 1:5, added to each well, and then the plate was read at 595 nm. For triglycerides, free glycerol and triglyceride reagents were added to each well, the plate was incubated at 37°C, and the optic density was read at 540 nm [45, 46]. …”

Section: Methodsmentioning

confidence: 99%

Rpd3 interacts with insulin signaling in Drosophila longevity extension

Woods

Ziafazeli

Rogina

2016

Aging

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Histone deacetylase (HDAC) 1 regulates chromatin compaction and gene expression by removing acetyl groups from lysine residues within histones. HDAC1 affects a variety of processes including proliferation, development, metabolism, and cancer. Reduction or inhibition of Rpd3, yeast and flyHDAC1 orthologue, extends longevity. However, the mechanism of rpd3's effects on longevity remains unclear. Here we report an overlap between rpd3 and the Insulin/Insulin-like growth factor signaling (IIS) longevity pathways. We demonstrated that rpd3 reduction downregulates expression of members of the IIS pathway, which is associated with altered metabolism, increased energy storage, and higher resistance to starvation and oxidative stress. Genetic studies support the role of IIS in rpd3 longevity pathway, as illustrated with reduced stress resistance and longevity of flies double mutant for rpd3 and dfoxo, a downstream target of IIS pathway compared to rpd3 single mutant flies. Our data suggest that increased dfoxo is a mediator of rpd3's effects on fly longevity and intermediary metabolism, and confer a new link between rpd3 and IIS longevity pathways.

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“…Moreover, Indy mRNA was shown to be downregulated in diet-restricted healthy flies, and Indy-mutated long-lived flies share several phenotypes with long-lived caloric-restricted flies. Therefore, NaCT has been proposed to regulate the aging processes at least in part by activating an AMP-activated protein kinase/peroxisome proliferator-activated receptor g coactivator 1a network (Rogina et al, 2000;Neretti et al, 2009;Wang et al, 2009;Rogers and Rogina, 2014;Schwarz et al, 2015). b. Solute carrier 13A5 genetic variants.…”

Section: Skeletal Musclementioning

confidence: 99%