Heat shock factor 1 mediates the longevity conferred by inhibition of TOR and insulin/IGF‐1 signaling pathways in <i>C. elegans</i>

Seo, Keunhee; Choi, Eun-Chang; Lee, Dong-Yeop; Jeong, Dae‐Eun; Jang, Sung Key; Lee, Seung-Jae

doi:10.1111/acel.12140

Cited by 114 publications

(98 citation statements)

References 46 publications

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“…Lifespan assays were performed as described previously with some modifications (Seo et al ., 2013). Briefly, synchronized young adult worms were transferred onto 5 μ m 5‐fluoro‐2′‐deoxyuridine (FUdR, Sigma, St. Louis, MO, USA)‐treated NGM plates with E. coli food.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of elongin C promotes longevity and protein homeostasis via HIF‐1 in C. elegans

et al. 2015

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SummaryThe transcription factor hypoxia‐inducible factor 1 (HIF‐1) is crucial for responses to low oxygen and promotes longevity in Caenorhabditis elegans. We previously performed a genomewide RNA interference screen and identified many genes that act as potential negative regulators of HIF‐1. Here, we functionally characterized these genes and found several novel genes that affected lifespan. The worm ortholog of elongin C, elc‐1, encodes a subunit of E3 ligase and transcription elongation factor. We found that knockdown of elc‐1 prolonged lifespan and delayed paralysis caused by impaired protein homeostasis. We further showed that elc‐1 RNA interference increased lifespan and protein homeostasis by upregulating HIF‐1. The roles of elongin C and HIF‐1 are well conserved in eukaryotes. Thus, our study may provide insights into the aging regulatory pathway consisting of elongin C and HIF‐1 in complex metazoans.

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Section: Methodsmentioning

confidence: 99%

Inhibition of elongin C promotes longevity and protein homeostasis via HIF‐1 in C. elegans

et al. 2015

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“…qRT-PCR was performed as described previously (Seo et al 2013). Synchronized worms treated with sbp-1 RNAi or mdt-15 RNAi from eggs with or without 2% glucose treatment were harvested at young adult stage (day 1) with M9 buffer by washing three times.…”

Section: Quantitative Rt-pcr (Qrt-pcr)mentioning

confidence: 99%

SREBP and MDT-15 protect C. elegans from glucose-induced accelerated aging by preventing accumulation of saturated fat

et al. 2015

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Glucose-rich diets shorten the life spans of various organisms. However, the metabolic processes involved in this phenomenon remain unknown. Here, we show that sterol regulatory element-binding protein (SREBP) and mediator-15 (MDT-15) prevent the life-shortening effects of a glucose-rich diet by regulating fat-converting processes in Caenorhabditis elegans. Up-regulation of the SREBP/MDT-15 transcription factor complex was necessary and sufficient for alleviating the life-shortening effect of a glucose-rich diet. Glucose feeding induced key enzymes that convert saturated fatty acids (SFAs) to unsaturated fatty acids (UFAs), which are regulated by SREBP and MDT-15. Furthermore, SREBP/MDT-15 reduced the levels of SFAs and moderated glucose toxicity on life span. Our study may help to develop strategies against elevated blood glucose and free fatty acids, which cause glucolipotoxicity in diabetic patients.

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“…Heat stress resistance assays were performed as previously described, with minor modifications (58). Synchronized eggs were allowed to develop on control RNAi plates until they reached L4 stage.…”

Section: Dod-11mentioning

confidence: 99%

RNA helicase HEL-1 promotes longevity by specifically activating DAF-16/FOXO transcription factor signaling in Caenorhabditis elegans

Seo

Hwang

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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The homeostatic maintenance of the genomic DNA is crucial for regulating aging processes. However, the role of RNA homeostasis in aging processes remains unknown. RNA helicases are a large family of enzymes that regulate the biogenesis and homeostasis of RNA. However, the functional significance of RNA helicases in aging has not been explored. Here, we report that a large fraction of RNA helicases regulate the lifespan of Caenorhabditis elegans. In particular, we show that a DEAD-box RNA helicase, helicase 1 (HEL-1), promotes longevity by specifically activating the DAF-16/forkhead box O (FOXO) transcription factor signaling pathway. We find that HEL-1 is required for the longevity conferred by reduced insulin/insulin-like growth factor 1 (IGF-1) signaling (IIS) and is sufficient for extending lifespan. We further show that the expression of HEL-1 in the intestine and neurons contributes to longevity. HEL-1 enhances the induction of a large fraction of DAF-16 target genes. Thus, the RNA helicase HEL-1 appears to promote longevity in response to decreased IIS as a transcription coregulator of DAF-16. Because HEL-1 and IIS are evolutionarily well conserved, a similar mechanism for longevity regulation via an RNA helicase-dependent regulation of FOXO signaling may operate in mammals, including humans.arious genetic and environmental factors, including insulin/ insulin-like growth factor 1 (IGF-1) signaling (IIS), target of rapamycin signaling, dietary restriction, mitochondrial respiration, and reproductive systems, influence aging across phyla (reviewed in refs. 1-3). IIS is one of the most evolutionarily conserved pathways involved in the regulation of aging. Mutations in Caenorhabditis elegans daf-2, which encodes an insulin/IGF-1 receptor homolog, double the lifespan of C. elegans (4). Inhibition of DAF-2 reduces phosphatidylinositide 3 (PI3)-kinase signaling, which upregulates several transcription factors, including DAF-16/forkhead box O (FOXO), heat shock factor-1 (HSF-1), and SKN-1/NRF2 (reviewed in refs. 1, 3, and 5). DAF-16 is one of the best characterized of these longevity factors; reduced PI3-kinase signaling leads to the dephosphorylation and nuclear translocation of DAF-16, which up-regulates the expression of various target genes. DAF-16 target genes contribute to longevity by promoting stress resistance, reproductive span, innate immunity, and protein homeostasis.RNA helicases are essential for biogenesis, maturation, processing, and homeostasis of various types of RNAs (reviewed in ref. 6). In addition, RNA helicases work with factors, such as a CREBbinding protein, RNA polymerases I and II, and histone deacetylases, to regulate transcriptional activity (7,8). For example, DDX5 (p68), a DEAD-box RNA helicase, interacts with Smad3, a transcriptional activator and intracellular effector of TGF-β (9), and with RNA polymerase II to modulate transcriptional activity (10). Because RNA helicases comprise a large family of housekeeping proteins essential for RNA biogenesis and homeostasis, their importanc...

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Heat shock factor 1 mediates the longevity conferred by inhibition of TOR and insulin/IGF‐1 signaling pathways in C. elegans

Cited by 114 publications

References 46 publications

Inhibition of elongin C promotes longevity and protein homeostasis via HIF‐1 in C. elegans

Inhibition of elongin C promotes longevity and protein homeostasis via HIF‐1 in C. elegans

SREBP and MDT-15 protect C. elegans from glucose-induced accelerated aging by preventing accumulation of saturated fat

RNA helicase HEL-1 promotes longevity by specifically activating DAF-16/FOXO transcription factor signaling in Caenorhabditis elegans

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