Jiang S et al. (2021) Food Funct "Rhodiola extract promotes longevity and stress resistance of Caenorhabditis elegans via DAF-16 and SKN-1."

Jiang S, Deng N, Liu RH, Zheng B, Li T

[Food Funct, 2021]

The effects of Rhodiola extract (RE) on longevity and stress resistance in Caenorhabditis elegans (C. elegans), and the underlying molecular mechanisms were explored in the present study. Results showed that the lifespan of C. elegans was remarkably prolonged by 37.1% after treated with high-dose RE (480 g mL-1). Intervention with RE alleviated aging-related declines in the C. elegans model, and enhanced the stress resistance against heat shock, ultraviolet radiation and paraquat. Moreover, RE reduced the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) and increased the activities of superoxide dismutase (SOD) and catalase (CAT). RE also upregulated the gene expression of sod-3, gst-4, daf-16, skn-1 in C. elegans, downregulated the gene expression of daf-2 and age-1, and accelerated the translocation of DAF-16 and SKN-1 into the nucleus. Furthermore, the daf-16(mu86) and skn-1(zu169) mutants reversed the extension of lifespan triggered by RE, indicating that these genes were involved in RE-regulated longevity. These results demonstrated that RE could enhance lifespan extension, healthspan and stress resistance of C. elegans via insulin/IGF signaling and SKN-1 pathways. Therefore, the present findings suggested Rhodiola as a potential candidate to ameliorate the symptoms of aging.

Wakabayashi T et al. (2020) Biol Trace Elem Res "Multiple Chemosensory Neurons Mediate Avoidance Behavior to Rare Earth Ions in Caenorhabditis elegans."

Wakabayashi T, Nojiri Y, Takahashi-Watanabe M

[Biol Trace Elem Res, 2020]

As rare earth (RE) metals are abundantly present in the soil, in spite of their name, it is conceivable that organisms may encounter and interact with RE ions. In the present study, we demonstrated that the soil nematode Caenorhabditis elegans avoids RE ions, such as yttrium and all examined lanthanide ions, which exhibit toxic effects on nematodes. We also demonstrated that the chemosensory system of this animal mediates avoidance behavior toward RE ions similar to heavy metal (HM) ion avoidance. The C. elegans dyf-11(pe554) mutant is unable to respond to chemosensory cues because it lacks all ciliated endings of the chemosensory neurons required for the detection of environmental chemicals. Cell-specific rescue of the dyf-11 mutant and cell-specific genetic ablation studies revealed that the avoidance behavior toward HM and RE ions was mediated by a partially overlapping but distinct subset of chemosensory neurons (ASH, ADL, ASE, ADF, and ASK). With the help of multiple chemosensory neurons, worms may improve the fidelity of avoidance behavior to evade RE ions. Among the chemosensory neurons in C. elegans, ADF and ASK neurons were involved in RE avoidance, but not in HM avoidance. These results suggested that ADF and ASK neurons in C. elegans have RE-selective mechanisms to mediate the avoidance response.

LaRocca TJ et al. (2020) Aging Cell "Repetitive elements as a transcriptomic marker of aging: Evidence in multiple datasets and models."

Wahl D, LaRocca TJ, Cavalier AN

[Aging Cell, 2020]

Transcriptomic markers of aging can be useful for studying age-related processes and diseases. However, noncoding repetitive element (RE) transcripts, which may play an important role in aging, are commonly overlooked in transcriptome studies-and their potential as a transcriptomic marker of aging has not been evaluated. Here, we used multiple RNA-seq datasets generated from human samples and Caenorhabditis elegans and found that most RE transcripts (a) accumulate progressively with aging; (b) can be used to accurately predict age; and (c) may be a good marker of biological age. The strong RE/aging correlations we observed are consistent with growing evidence that RE transcripts contribute directly to aging and disease.

Fay, Samuel F. et al. MicroPubl Biol

Chhatre, Vikram E., Fay, David S., Fay, Samuel F.

[MicroPubl Biol, 2021]

CRISPR/Cas9 genome editing strategies often rely on the placement of an introduced restriction endonuclease (RE) site adjacent to the genomic edit of interest. This allows for rapid initial PCR-based detection of cells and organisms containing the edit of interest and may also be used for subsequent genotyping. Nevertheless, engineering RE sites at optimal locations within coding regions can be difficult due to the many hundreds of potential endonuclease options and the strict requirement to maintain the correct amino acid sequence. Here we report CRISPRcruncher, a computational tool that analyzes an input coding sequence and produces a complete list of all possible changes that could be made that will create new RE sites while preserving the original peptide sequence. Notably, for sequences tested, CRISPRcruncher identified approximately one new RE site per input nucleotide when mining for 4-bp or longer RE motifs and 0.5 new RE sites per input nucleotide when mining for 6-bp or longer motifs. Therefore, CRISPRcruncher represents a powerful new computational tool in the CRISPR arsenal.

Wakabayashi T et al. (2018) Biol Trace Elem Res "Stress Responses Against Rare Earth Ions Are Mediated by the JNK and p38 MAPK Pathways in Caenorhabditis elegans."

Nakano Y, Wakabayashi T

[Biol Trace Elem Res, 2018]

Rare earth (RE) ions at high concentrations are toxic to many organisms as they induce oxidative stress and cause improper incorporation of the ions into calcium-binding proteins. Although the mechanism of action underlying the toxicity of REs has been identified, intracellular signaling pathways involved in stress responses against RE ions still remain unclear. In Caenorhabditis elegans, cellular responses against heavy metal stresses are primarily regulated by the c-Jun N-terminal kinase (JNK)-like mitogen-activated protein kinase (MAPK) pathway with a minor contribution of the p38-like MAPK pathway. In this study, we found that both JNK- and p38-like MAPK pathways were involved in stress responses against RE. Unlike heavy metal responses, mutations in both the JNK and p38 pathways caused similar hypersensitivity to RE ions. Although the signaling pathways used for these stress responses were found to be similar, the degree of their respective contribution slightly differed between heavy metal and RE ions.

Meserve JH et al. (2021) Elife "Deciding when to exit."

Duronio RJ, Meserve JH

[Elife, 2021]

A new imaging approach can distinguish between cells destined to stop proliferating and those committed to re-entering the cell cycle in live animals.

Palmer RE et al. (1994) Worm Breeder's Gazette "Use of an Expression Library to Clone Genes by Complementation"

Palmer RE, Sternberg PW

[Worm Breeder's Gazette, 1994]

Use of an expression library to clone genes by complemcntation. RE. Palmer and P.W. Sternberg, HHMI and Division of Biology, Caltech, Pasadena, CA 91125

Khan MA et al. (2004) Ann Trop Med Parasitol "Responses of Mastomys coucha, that have been infected with Brugia malayi and treated with diethylcarbamazine or albendazole, to re-exposure to infection."

Saleemuddin M, Gaur RL, Dixit S, Khan MA, Murthy PK

[Ann Trop Med Parasitol, 2004]

The responses of Mastomys coucha to re-exposure to infection with homologous infective larvae (L(3)) of Brugia malayi were investigated, after initial infections with the nematode had been treated subcutaneously for 5 days with diethylcarbamazine (DEC; 150 mg citrate/kg. day) or albendazole (ALB; 50 mg/kg. day). The parasite burdens, serum concentrations of IgG reacting with a soluble somatic extract of adult B. malayi (BmAS), and cytokine and lymphocyte-proliferative responses to filarial antigen (BmAS) or mitogen (concanavilin A or lipopolysaccharide) were studied. The results demonstrated, for the first time, that re-infection with L(3) was only successful in the DEC-treated animals, not the ALB-treated ones. When the ALB-treated animals were re-exposed, interferon-gamma production decreased, lymphocyte-proliferative responses either remained the same (with concanavilin A) or decreased (with BmAS), and concentrations of specific IgG decreased. When the DEC-treated animals were re-exposed, microfilaraemias re-appeared and, although production of interferon-gamma decreased, there were no detectable lymphocyte proliferative responses, and concentrations of specific IgG remained unchanged. Taken together, the results indicate that, at least in the M. coucha model of human filariasis, ALB but not DEC treatment may help to prevent the development of re-infections.

Kumar R et al. (2013) Ann Neurosci "Withania somnifera root extract extends lifespan of Caenorhabditis elegans."

Kumar R, Saharia K, Pradhan D, Gupta K, Subramaniam JR

[Ann Neurosci, 2013]

BACKGROUND: In the ancient Indian herbal medicine system several ayurvedic preparations are claimed to have longevity enhancing effects. But, so far, no clear scientific evidence has been provided. One among them, is the roots of the plant, commonly known as Ashwagandha (Withania somnifera Dunal- WSD), which is supposed to have myriad of beneficial effects including long life. PURPOSE: Here, we evaluated both the root extract (RE) and its purified ingredients (PI-RE) with a similar composition as in RE obtained from the roots of WSD for lifespan extension in the well established model system, C. elegans. PI-RE could extend the lifespan of C. elegans. METHODS: We used wild type C. elegans (N2) or RB918: acr-16 (ok789); andNL2099: rrf-3 (pk1426) mutant worms and analysed their lifespan assay in Ashwagandha extract spreaded on plates containing Bacterial Lawns. RESULTS: Strangely, while there was no effect on the wild type worms, the mutant for the human nicotinic acetylcholine receptor, nAchR, 7 equivalent, acr-16, showed around ~20% lifespan extension when treated with PI-RE. CONCLUSION: Thus, we are able to show that one of the age old healthy longlife supplements, Ashwagandha does extend lifespan of C. elegans.

Park, Eun Chan et al. (2013) International Worm Meeting "Mitochondrial Dynamics And Behavioral Plasticity In Response To Oxygen Deprivation Are Linked Through HIF-1."

Salazar-Vasquez, Nathaly, Ghose, Piya, Park, Eun Chan, Tabakin, Alexandra, Rongo, Christopher

[International Worm Meeting, 2013]

C. elegans can survive extreme oxygen deprivation (anoxia, < 0.1% O2) by entering into a suspended animation state during which locomotory behavior and development arrest. Upon re-exposure to normoxic conditions (21 % O2), animals resume their behavior and normal development. The underlying mechanism of this stress response is not well understood. Here we show that neuronal mitochondria undergo fission in response to anoxia co-temporaneously with the onset of suspended animation, followed by re-fusion upon re-oxygenation, suggesting that mitochondrial dynamics might contribute to anoxia-induced suspended animation. We find that the hypoxia response pathway, including EGL-9 and HIF-1, regulates the reconstitution of mitochondria following re-oxygenation. Under conditions of normal oxygen, EGL-9 represses the activity of HIF-1, a transcription factor that promotes the expression of hypoxia-response genes. Loss of function mutations in egl-9 result in rapid re-fusion of mitochondria and behavioral recovery from suspended animation following re-oxygenation; both phenotypes require HIF-1 activity. In addition, the mitochondria are significantly larger in egl-9 mutants after re-oxygenation than they were prior to anoxia exposure - a phenotype that resembles the stress-induced mitochondria hyperfusion (SIMH) that has been observed in mammalian cells. Both the changes in mitochondrial dynamics and suspended animation recovery of egl-9 mutants can be rescued by expressing wild-type EGL-9 solely in neurons. Mitochondrial hyperfusion and rapid recovery observed in egl-9 mutants following anoxia are modulated by STL-1, a mammalian stomatin-like protein (SLP2) homologue that is reported to function in SIMH. Our results suggest the existence of a conserved stress response involving changes in mitochondrial fission and fusion, and demonstrate that the behaviors executed by a simple neural circuit can be regulated through changes in mitochondrial dynamics.