Anderson, Edward N. et al. (2011) International Worm Meeting "Osmotic stress and loss of Notch ligands extend C. elegans lifespan via FOXO and sirtuins."

Corkins, Mark, Sinclair, David, Anderson, Edward N., Hart, Anne C.

[International Worm Meeting, 2011]

Moderate environmental stress, such as oxidative stress, dietary restriction, or heat shock, can increase the lifespan of many species. In S. cerevisiae, moderate osmotic stress causes lifespan extension, and this extension requires sirtuin function in the NAD salvage pathway. (Kaeberlein et al. 2002). We find that moderate osmotic stress increases the lifespan of C. elegans. NGM contains 51 mM NaCl as the major osmolyte. Wild type animals reared on NGM with increased NaCl live longer than those reared on standard 51 mM NaCl. This lifespan extension occurs with other osmolytes and is dose-dependent. Maximal lifespan extension of 30% is observed at 300 mM NaCl. Osmotic stress starting after the L4 stage is sufficient to extend lifespan. Currently, we are investigating the underlying genetic pathways. Osmotic stress induced lifespan extension requires members of the sirtuin family and the FOXO transcription factor daf-16. We also find a partial requirement for pnc-1, a component of the NAD salvage pathway. Loss of Notch co-ligands osm-7 and osm-11 mimics osmotic stress and extends lifespan in a daf-16 dependent manner. Dietary restriction by eat-2 does not further extend lifespan under osmotic stress conditions. Overall, our results suggest that osmotic stress likely extends lifespan by activating conserved pathways.

Kipreos ET et al. (1992) Worm Breeder's Gazette "Cloning of the C. elegans Tumor Suppressor Genes lin-19 and lin-23"

Hedgecock EM, Kipreos ET

[Worm Breeder's Gazette, 1992]

Cloning of the C. elegans tumor suppressor genes lin-l9 and lin-23. Edward T. Kipreos and Edward M. Hedgecock Department of Biology, Johns Hopkins University, Baltimore, MD 21218

Plenefisch JD et al. (1994) Worm Breeder's Gazette "Cloning mua-3: Some Observations on the New Molecular Era"

Plenefisch JD, Hedgecock EM

[Worm Breeder's Gazette, 1994]

Cloning mua-3: some observations on the new Molecular Era John Plenefisch and Edward Hedgecock, Dept. of Biology, Johns Hopkins University, Baltimore MD 21218

Eve A (2021) Development "An interview with Swathi Arur."

Eve A

[Development, 2021]

Swathi Arur is an Associate Professor for the Department of Genetics at the MD Anderson Cancer Center, USA, where she uses multidisciplinary approaches to understand female germline development and fertility. She has received numerous accolades, including the MD Anderson Distinguished Research Faculty Mentor Award in 2017. In 2020, she was elected to the American Association for the Advancement of Science (AAAS). Swathi joined the team at Development as an Academic Editor in 2020, and we met with her over Zoom to hear more about her life, her career and her love for <i>C. elegans</i>.

Dixon JR (2019) Dev Cell "TADs for Life: Chromatin Domain Organization Regulates Lifespan in C.elegans."

Dixon JR

[Dev Cell, 2019]

In this issue of Developmental Cell, Anderson etal. (2019) show that chromatin domain structure on the X chromosome in C.elegans is dispensable for dosage compensation but regulates longevity and thermotolerance. This study sheds light on the mechanisms of domain formation in C.elegans and how these features affect physiology.

Corkins, Mark et al. (2009) International Worm Meeting "Osmotic stress extends C. elegans lifespan."

Somers, Gerard, Hart, Anne C., Anderson, Edward N., Corkins, Mark

[International Worm Meeting, 2009]

Moderate levels of environmental stress, such as oxidative stress, dietary restriction, or heat shock, can cause organisms to live longer. In S. cerevisiae, osmotic stress has been shown to cause lifespan extension, and this extension is regulated by sirtuins via the NAD salvage pathway. (Kaeberlein et al. 2002). We find that moderate osmotic stress can increase the lifespan of C. elegans. The major osmolyte in NGM media is NaCl. Wild type animals reared on NGM containing increased NaCl live longer than those reared on standard 51 mM NaCl. This increased lifespan extension is dose-dependant, and maximal lifespan is observed at roughly 300 mM NaCl with approximately 30% lifespan extension. Increased longevity is likely not due to a developmental change, animals shifted at the L4 stage to 300 mM NaCl have a lifespan similar to those reared from birth on 300 mM media. Currently, we are assessing the contribution of genes known to extend lifespan in this paradigm. Osmotic stress induced lifespan extension is prevented by loss of the FOXO transcription factor daf-16, but is unaffected by loss of the AMP kinase aak-2. Osmotic lifespan extension is not further extended by the eat-2 model of dietary restriction. Overall, our results suggest that osmotic stress can increase longevity and that a subset of conserved pathways are critical for this lifespan extension.

Levin ED et al. (2009) Neurotoxicology "Genetic aspects of behavioral neurotoxicology."

Kirshner A, Eddins D, French R, Helmcke K, Page GP, Linney E, Lnenicka G, Berger K, Welsh-Bohmer KA, Corl AB, Levin ED, Hirsch HV, Aschner M, Bartlett S, Possidente B, Hayden KM, Chen L, Possidente D, Ruden D, Heberlein U

[Neurotoxicology, 2009]

Considerable progress has been made over the past couple of decades concerning the molecular bases of neurobehavioral function and dysfunction. The field of neurobehavioral genetics is becoming mature. Genetic factors contributing to neurologic diseases such as Alzheimer's disease have been found and evidence for genetic factors contributing to other diseases such as schizophrenia and autism are likely. This genetic approach can also benefit the field of behavioral neurotoxicology. It is clear that there is substantial heterogeneity of response with behavioral impairments resulting from neurotoxicants. Many factors contribute to differential sensitivity, but it is likely that genetic variability plays a prominent role. Important discoveries concerning genetics and behavioral neurotoxicity are being made on a broad front from work with invertebrate and piscine mutant models to classic mouse knockout models and human epidemiologic studies of polymorphisms. Discovering genetic factors of susceptibility to neurobehavioral toxicity not only helps identify those at special risk, it also advances our understanding of the mechanisms by which toxicants impair neurobehavioral function in the larger population. This symposium organized by Edward Levin and Annette Kirshner, brought together researchers from the laboratories of Michael Aschner, Douglas Ruden, Ulrike Heberlein, Edward Levin and Kathleen Welsh-Bohmer conducting studies with Caenorhabditis elegans, Drosophila, fish, rodents and humans studies to determine the role of genetic factors in susceptibility to behavioral impairment from neurotoxic exposure.

Moroz, Natalie et al. (2015) International Worm Meeting "Dietary restriction involves NAD+-dependent mechanisms and a shift towards oxidative metabolism."

Hart, Anne, Sinclair, David, Blackwell, Keith, Anderson, Edward, Carmona, Juan, Moroz, Natalie

[International Worm Meeting, 2015]

Interventions that slow aging and prevent chronic disease may come from an understanding of how dietary restriction (DR) increases lifespan. Mechanisms proposed to mediate DR longevity include reduced mTOR signaling, activation of the NAD+-dependent deacylases known as sirtuins, and increases in NAD+ that derive from higher levels of respiration. Here we explored these hypotheses in Caenorhabditis elegans using a new liquid feeding protocol. DR lifespan extension depended upon a group of regulators that are involved in stress responses and mTOR signaling, and have been implicated in DR by some other regimens (DAF-16 (FOXO), SKN-1 (Nrf1/2/3), PHA-4 (FOXA), AAK-2 (AMPK)). Complete DR lifespan extension required the sirtuin SIR-2.1 (SIRT1), the involvement of which in DR has been debated. The nicotinamidase PNC-1, a key NAD+ salvage pathway component, was largely required for DR to increase lifespan but not two healthspan indicators: movement and stress resistance. Independently of pnc-1, DR increased the proportion of respiration that is coupled to ATP production but, surprisingly, reduced overall oxygen consumption. We conclude that stress response and NAD+-dependent mechanisms are each critical for DR lifespan extension, although some healthspan benefits do not require NAD+ salvage. Under DR conditions, NAD+-dependent processes may be supported by a DR-induced shift towards oxidative metabolism rather than an increase in total respiration. JC and EA contributed equally. AH, DS, and KB are co-corresponding authors.

Bennett, Heather L et al. (2011) International Worm Meeting "A role for heterochronic genes in regulating C.elegans quiescence."

Corkins, Mark E, Anderson, Edward, Singh, Komudi, Hart, Anne C, Bennett, Heather L

[International Worm Meeting, 2011]

Sleep is an essential biological process that is regulated by circadian rhythms, homeostatic regulation and arousal threshold. The nematode Caenorhabitdis elegans undergoes a sleep-like state called quiescence that accompanies each larval molt (Raizen et al., 2008). Many pathways regulate larval development, including heterochronic genes and the Notch signaling pathway. Heterochronic genes control timing of cell differentiation and molting of larval cuticle. In Drosophila, circadian rhythm proteins cycle to regulate sleep behavior. In C.elegans, circadian rhythm homologs in the heterochronic pathway regulate the fusion of hypodermal seam cells during late development (Jeon et al., 1999, Banerjee et al., 2005). Recently, a temporal role in C. elegans molting was suggested for the Notch signaling pathway. Gain of function alleles of a Notch receptor gene, lin-12, result in precocious cell fate changes (Solomon et al., 2007). We have found that Notch also plays a role in the regulation of quiescence. Increased or decreased Notch signaling results in increased quiescence and altered arousal thresholds during the last larval stage (L4) to adult (A) transition (Singh et al., in press). However, the connection between circadian rhythm homologs, heterochronic genes, and Notch in the regulation of quiescence remains unclear. We are assessing gain and loss of function alleles of heterochronic genes acting in the L4/A transition to determine if they play a role in regulating quiescence. Demonstrating a genetic interaction between heterochronic genes, circadian rhythm proteins, and the Notch signaling pathway will be the first step in delineating mechanisms that coordinate cell fate and behavioral changes during development.

Antol, Weronika et al. (2022) MicroPubl Biol

Sychta, Karolina, Prokop, Zofia M., Antol, Weronika, Palka, Joanna K., Dudek, Katarzyna

[MicroPubl Biol, 2022]

Caenorhabditis elegans is a model species, increasingly used in experimental evolution studies to investigate such major topics as: maintenance of genetic variation, host-pathogen interaction and coevolution, mutations, life history, evolution of reproductive systems, sexual selection (Gray and Cutter, 2014; Teotnio, Estes, Phillips, and Baer, 2017). Its reproductive system in the wild, known as androdioecy, involves mostly self-fertilization of hermaphrodites and occasionally outcrossing with males, which are generally rare (Stewart and Phillips, 2002). This system can be experimentally changed to dioecy, i.e., obligatory outcrossing, through genetic manipulations (see Table I in Anderson, Morran, and Phillips, 2010; Gray and Cutter, 2014).