Lee D et al. (2019) PLoS Biol "MDT-15/MED15 permits longevity at low temperature via enhancing lipidostasis and proteostasis."

Taubert S, Lee Y, Beigi A, Yang JS, Jung Y, Ryu Y, Ma DK, Goh GYS, Yamaoka Y, An SWA, Ha CM, Lee SV, Lee D, Jung GY

[PLoS Biol, 2019]

Low temperatures delay aging and promote longevity in many organisms. However, the metabolic and homeostatic aspects of low-temperature-induced longevity remain poorly understood. Here, we show that lipid homeostasis regulated by Caenorhabditis elegans Mediator 15 (MDT-15 or MED15), a transcriptional coregulator, is essential for low-temperature-induced longevity and proteostasis. We find that inhibition of mdt-15 prevents animals from living long at low temperatures. We show that MDT-15 up-regulates fat-7, a fatty acid desaturase that converts saturated fatty acids (SFAs) to unsaturated fatty acids (UFAs), at low temperatures. We then demonstrate that maintaining a high UFA/SFA ratio is essential for proteostasis at low temperatures. We show that dietary supplementation with a monounsaturated fatty acid, oleic acid (OA), substantially mitigates the short life span and proteotoxicity in mdt-15(-) animals at low temperatures. Thus, lipidostasis regulated by MDT-15 appears to be a limiting factor for proteostasis and longevity at low temperatures. Our findings highlight the crucial roles of lipid regulation in maintaining normal organismal physiology under different environmental conditions.

Kumar GK (2016) Elife "Adapt or avoid."

Kumar GK

[Elife, 2016]

An enzyme called p38 MAP kinase helps nematodes to adapt to low-oxygen environments, and also to escape from them.

Brys K et al. (2007) Exp Gerontol "Testing the rate-of-living/oxidative damage theory of aging in the nematode model Caenorhabditis elegans."

Brys K, Braeckman BP, Vanfleteren JR

[Exp Gerontol, 2007]

The integration of the rate-of-living and oxidative damage theory of aging predicts that lifespan extension is linked to low energy metabolism, low ROS production rates, low molecular damage and a slow aging rate. In the long-lived Caenorhabditis elegans Ins/IGF-1 mutant daf-2(e1370), low carbonylation levels and postponed morphological decline comply with the latter two of these predictions. However, metabolic rates in daf-2(e1370) refute the rate-of-living theory. The apparent contradiction between increased ROS generation and long lifespan in daf-2(e1370) is reconciled by an enhanced stress defense, acknowledging oxidative damage as a probable cause of aging.

Kage-Nakadai E et al. (2014) Methods "Methods for single/low-copy integration by ultraviolet and trimethylpsoralen treatment in Caenorhabditis elegans."

Imae R, Mitani S, Yoshina S, Kage-Nakadai E

[Methods, 2014]

Single/low-copy transgene integration is essential for avoiding overexpression, ectopic expression and gene silencing in the germline. Here, we present an overview of a method that uses ultraviolet and trimethylpsoralen (UV/TMP) to generate single/low-copy gene integrations in Caenorhabditis elegans. Single/low-copy transgenes from extrachromosomal arrays are integrated into the genome using positive selection based on temperature sensitivity with a vps-45 rescue fragment and negative selection based on benzimidazole sensitivity with a ben-1 rescue fragment. The copy number of the integrated transgenes is determined using quantitative PCR. Our UV/TMP integration method, which is based on familiar extrachromosomal transgenics, provides a simple approach for generating single/low-copy gene integrations.

Kage-Nakadai, Eriko et al. (2011) International Worm Meeting "Low-copy integration of transgenes by TMP/UV methods."

Yoshina, Sawako, Gengyo-Ando, Keiko, Kage-Nakadai, Eriko, Kobuna, Hiroyuki, Funatsu, Osamu, Mitani, Shohei, Ootori, Muneyoshi, Hori, Sayaka

[International Worm Meeting, 2011]

In Caenorhabditis elegans, transgenic strains are typically generated by injecting DNA into the germline to form high-copy extrachromosomal arrays. These transgenes are semi-stable and their expression are silenced in germline. In order to create single- or low-copy chromosomal integrated lines, methods using Mos1 transposon or microparticle bombardment have been developed. We have developed an alternative method by using TMP/UV, that produces low-copy integrations. We have successfully integrated low-copy of transgenes using positive selection with vps-45 rescue fragment / temperature sensitivity and negative selection with ben-1 rescue fragment / benomyl sensitivity. We confirmed that low-copy integrants express transgenes in germline. Currently, using this method, we are constructing a PhiC31-attBP / Cre-LoxP system.

Li Y et al. (2019) Front Microbiol "Anticandidal Activity of Kalopanaxsaponin A: Effect on Proliferation, Cell Morphology, and Key Virulence Attributes of Candida albicans."

Zhu Z, Li Y, Shan M, Yao H, Yan M, Wang Y, Li H, Gu B

[Front Microbiol, 2019]

Background: . Methods: . Results: and a low possibility of developing resistance. Conclusion: pathogenicity, suggesting that it could be a potential option for the clinical treatment of candidiasis.

Dietrich N et al. (2017) Nucleic Acids Res "A pathway for low zinc homeostasis that is conserved in animals and acts in parallel to the pathway for high zinc homeostasis."

Kornfeld K, Schneider DL, Dietrich N

[Nucleic Acids Res, 2017]

The essential element zinc plays critical roles in biology. High zinc homeostasis mechanisms are beginning to be defined in animals, but low zinc homeostasis is poorly characterized. We investigated low zinc homeostasis in Caenorhabditis elegans because the genome encodes 14 evolutionarily conserved Zrt, Irt-like protein (ZIP) zinc transporter family members. Three C. elegans zipt genes were regulated in zinc-deficient conditions; these promoters contained an evolutionarily conserved motif that we named the low zinc activation (LZA) element that was both necessary and sufficient for activation of transcription in response to zinc deficiency. These results demonstrated that the LZA element is a critical part of the low zinc homeostasis pathway. Transcriptional regulation of the LZA element required the transcription factor ELT-2 and mediator complex member MDT-15. We investigated conservation in mammals by analyzing LZA element function in human cultured cells; the LZA element-mediated transcriptional activation in response to zinc deficiency in cells, suggesting a conserved pathway of low zinc homeostasis. We propose that the pathway for low zinc homeostasis, which includes the LZA element and ZIP transporters, acts in parallel to the pathway for high zinc homeostasis, which includes the HZA element, HIZR-1 transcription factor and cation diffusion facilitator transporters.

Kage-Nakadai E et al. (2012) BMC Biotechnol "Single/low-copy integration of transgenes in Caenorhabditis elegans using an ultraviolet trimethylpsoralen method."

Hori S, Gengyo-Ando K, Funatsu O, Otori M, Kobuna H, Yoshina S, Mitani S, Kage-Nakadai E

[BMC Biotechnol, 2012]

BACKGROUND: Transgenic strains of Caenorhabditis elegans are typically generated by injecting DNA into the germline to form multi-copy extrachromosomal arrays. These transgenes are semi-stable and their expression is silenced in the germline. Mos1 transposon or microparticle bombardment methods have been developed to create single- or low-copy chromosomal integrated lines. Here we report an alternative method using ultraviolet trimethylpsoralen (UV/TMP) to generate single/low-copy gene integrations. RESULTS: We successfully integrated low-copy transgenes from extrachromosomal arrays using positive selection based on temperature sensitivity with a vps-45 rescue fragment and negative selection based on benzimidazole sensitivity with a ben-1 rescue fragment. We confirmed that the integrants express transgenes in the germline. Quantitative PCR revealed that strains generated by this method contain single- or low-copy transgenes. Moreover, positive selection marker genes flanked by LoxP sites were excised by Cre recombinase mRNA microinjection, demonstrating Cre-mediated chromosomal excision for the first time in C. elegans. CONCLUSION: Our UV/TMP integration method, based on familiar extrachromosomal transgenics, provides a useful approach for generating single/low-copy gene integrations.

Wu, Ziyun et al. (2017) International Worm Meeting "An essential role for p38/ATF-7 pathway in survival under low potassium environment in C. elegans."

Blackwell, T. Keith, Wu, Ziyun

[International Worm Meeting, 2017]

Potassium ions are essential for all living cells. In humans, potassium levels have critical effects on action potentials, blood pressure, osmotic pressure, acid-base balance, metabolism and many other health parameters. Although C. elegans has frequently been employed to study the nervous system, genetics, development, metabolism and aging, how potassium levels affect C. elegans survival has not been investigated, the molecular mechanisms in regulation of survival in response to low potassium environment are unknown. Here we determined that the conserved p38 MAPK signaling pathway NSY-1(ASK1)- SEK-1(MKK3)-PMK-1(p38) is essential for C. elegans survival under low potassium conditions. Wild-type worms are not sensitive to low potassium environment and able to survive more than one month. By contrast, under these conditions animals in which this p38 pathway is disabled become paralyzed within two hours, and die within a few days. Through EMS mutagenesis screening of sek-1(km4) animals for resistance to low potassium, we determined that the p38 pathway mediates resistance to low potassium by regulating the transcription factor ATF-7. Additionally, pharmacological studies suggest that A-type K+ channels are critical for survival under low potassium conditions. The essential function of sek-1 in resistance to low potassium can be rescued by its expression specifically in the ASI chemosensory neurons and not the intestine, revealing that this function is distinct from the roles of sek-1 and p38 signaling in dietary restriction and pathogen resistance. Further genetic analyses in C. elegans may be invaluable for unraveling neuronal tissue-nonautonomous signaling mechanisms that maintain potassium homeostasis.

Liu P et al. (2024) Elife "UPRER-immunity axis acts as physiological food evaluation system that promotes aversion behavior in sensing low-quality food."

Liu P, Qi B, Liu X

[Elife, 2024]

To survive in challenging environments, animals must develop a system to assess food quality and adjust their feeding behavior accordingly. However, the mechanisms that regulate this chronic physiological food evaluation system, which monitors specific nutrients from ingested food and influences food-response behavior, are still not fully understood. Here, we established a low-quality food evaluation assay system and found that heat-killed <i>E. coli</i> (HK-<i>E. coli),</i> a low-sugar food, triggers cellular UPR^ER and immune response. This encourages animals to avoid low-quality food. The physiological system for evaluating low-quality food depends on the UPR^ER (IRE-1/XBP-1) - Innate immunity (PMK-1/p38 MAPK) axis, particularly its neuronal function, which subsequently regulates feeding behaviors. Moreover, animals can adapt to a low-quality food environment through sugar supplementation, which inhibits the UPR^ER -PMK-1 regulated stress response by increasing vitamin C biosynthesis. This study reveals the role of the cellular stress response pathway as physiological food evaluation system for assessing nutritional deficiencies in food, thereby enhancing survival in natural environments.