RNAi Interrogation of Dietary Modulation of Development, Metabolism, Behavior, and Aging in C. elegans

Xiao, Rui; Lei, Chun; Ronan, Elizabeth A.; Friedman, David I.; Liu, Jianfeng; Xu, Xiangru

doi:10.1016/j.celrep.2015.04.024

Cited by 99 publications

(110 citation statements)

References 65 publications

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“…When C. elegans is grown on the standard E. coli food OP50, inhibition of mTORC2 activity by mutation of its subunit gene rict-1 (Rictor) decreases lifespan [99,104,119]. This seems to be because neuronal mTORC2 is required in a little-understood skn-1 -independent pathway that promotes longevity at moderate and lower temperatures [99,120].…”

Section: Importance Of Skn-1 For Longevitymentioning

confidence: 99%

“…This seems to be because neuronal mTORC2 is required in a little-understood skn-1 -independent pathway that promotes longevity at moderate and lower temperatures [99,120]. In contrast, with feeding of certain other bacterial strains (such as HT115), the net effect of mTORC2 reduction on lifespan is positive [29,99,119], because under these conditions mTORC2 inhibition increases SKN-1 nuclear accumulation and target gene activation (Figs. 5A and 6B) [29,99].…”

Section: Importance Of Skn-1 For Longevitymentioning

confidence: 99%

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SKN-1/Nrf, stress responses, and aging in Caenorhabditis elegans

Blackwell

Steinbaugh

Hourihan

et al. 2015

Free Radical Biology and Medicine

442

481

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The mammalian Nrf/CNC proteins (Nrf1, Nrf2, Nrf3, p45 NF-E2) perform a wide range of cellular protective and maintenance functions. The most thoroughly described of these proteins, Nrf2, is best known as a regulator of antioxidant and xenobiotic defense, but more recently has been implicated in additional functions that include proteostasis and metabolic regulation. In the nematode Caenorhabditis elegans, which offers many advantages for genetic analyses, the Nrf/CNC proteins are represented by their ortholog SKN-1. Although SKN-1 has diverged in aspects of how it binds DNA, it exhibits remarkable functional conservation with Nrf/CNC proteins in other species and regulates many of the same target gene families. C. elegans may therefore have considerable predictive value as a discovery model for understanding how mammalian Nrf/CNC proteins function and are regulated in vivo. Work in C. elegans indicates that SKN-1 regulation is surprisingly complex and is influenced by numerous growth, nutrient, and metabolic signals. SKN-1 is also involved in a wide range of homeostatic functions that extend well beyond the canonical Nrf2 function in responses to acute stress. Importantly, SKN-1 plays a central role in diverse genetic and pharmacologic interventions that promote C. elegans longevity, suggesting that mechanisms regulated by SKN-1 may be of conserved importance in aging. These C. elegans studies predict that mammalian Nrf/CNC protein functions and regulation may be similarly complex and that the proteins and processes that they regulate are likely to have a major influence on mammalian life- and healthspan.

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Section: Importance Of Skn-1 For Longevitymentioning

confidence: 99%

Section: Importance Of Skn-1 For Longevitymentioning

confidence: 99%

SKN-1/Nrf, stress responses, and aging in Caenorhabditis elegans

Blackwell

Steinbaugh

Hourihan

et al. 2015

Free Radical Biology and Medicine

442

481

View full text Add to dashboard Cite

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“…We modified our standard system by substituting concentrated RNAi bacteria for the standard OP50 food and adding ampicillin and the IPTG inducing agent to the corral-NGM recipe. Figure 6 shows results using the RNAi-competent OP50-derivative xu363 as feeding bacteria; 46 we have observed equivalent effects using the standard RNAi strain HT115 (not shown). First, lifelong RNAi against GFP effectively knocks down fluorescence from a mir-1p::GFP transgenic strain relative to control RNAi (Fig.…”

Section: Resultsmentioning

confidence: 85%

“…Single colonies of RNAi bacteria (strain xu363) 46 were selected from a plate and inoculated overnight at 37°C with shaking, in LB supplemented with 100 mg/mL ampicillin. The overnight cultures were spun down and resuspended in M9 to 50% w / v and stored in aliquots at 4°C until use.…”

Section: Methodsmentioning

confidence: 99%

A simple culture system for long-term imaging of individual C. elegans

et al. 2017

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We have miniaturized standard culture techniques to rear arrays of isolated, individual C. elegans throughout their lives on solid gel media. The resulting apparatus is compatible with brightfield and fluorescent microscopy, enabling longitudinal studies of morphology and fluorescent transgene expression. Our culture system exploits a novel crosslinking reaction between a polyethylene glycol hydrogel and a silicone elastomer to constrain animals to individual “corrals” on the gel surface. These devices are simple to construct on the benchtop with commercially available reagents, and, unlike microfluidic isolation methods, does not rely on micropatterned materials. We demonstrate that this new culture method has negligible effects on the physiology of C. elegans compared to standard culture on agar plates. In addition, RNAi techniques are effective in this system. Finally, the hydrogel–silicone binding chemistry that we developed also allows traditional microfluidic devices to be covalently attached to gel substrates instead of glass.

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“…[38][39][40] Recently, a new RNAi competent bacterial strain derived from the OP50 background was generated. 41 Even though most, if not all, RNAi screens are far from being saturated -particularly those for aging and lifespan -this reagent will prove to be an extremely powerful tool to reprobe previously done RNAi screens to more fully identify genetic regulators of worm physiology. 42 C. elegans remains a premiere model to study the impact of diet -both composition and amount -on animal life history traits.…”

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confidence: 99%

The SKN-1 hunger games: May the odds be ever in your favor

Lynn

Curran

2015

Worm

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Animals must continually assess nutrient availability to develop appropriate strategies for survival and reproductive success. It is no secret that nutritional state plays a large role in both aging and health.(1-7) Appropriate cellular energy usage is not only crucial for animal starvation survival, but is also important for diseases such as obesity and cancer, which characteristically have metabolic dysfunction.(8-10) C. elegans are exceptionally well poised to handle bouts of starvation as resource availability in the wild varies greatly.(11,12) We recently discovered an evolutionarily conserved pathway, regulated by the cytoprotective transcription factor SKN-1/Nrf2, which integrates diet composition and availability with utilization for survival.(13,14) These responses have potent impact on organismal physiology and remarkably are influenced by current and parental life history events, including choice of diet. In this commentary we will focus on recent insights concerning dietary intake and the impact that this can have throughout the life history of the nematode, Caenorhabditis elegans. In light of the strong impact that diet plays throughout life we urge caution when interpreting previous studies that make use of only one diet and suggest a reinvestigation utilizing a different diet is warranted.

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RNAi Interrogation of Dietary Modulation of Development, Metabolism, Behavior, and Aging in C. elegans

Cited by 99 publications

References 65 publications

SKN-1/Nrf, stress responses, and aging in Caenorhabditis elegans

SKN-1/Nrf, stress responses, and aging in Caenorhabditis elegans

A simple culture system for long-term imaging of individual C. elegans

The SKN-1 hunger games: May the odds be ever in your favor

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