C22 disrupts embryogenesis and extends C. elegans lifespan

Caenorhabditis elegans is an instrumental model in aging research due to its large brood size, short lifespan, and malleable genetics. However, maintaining a synchronous nematode population for longevity studies is challenging and time consuming due to their quick rate of development and reproduction. Multiple methods are employed in the field, ranging from worm strains with temperature dependent sterility to DNA replication inhibitors such as 5′-fluorodeoxyuridine (FUdR). In this study, we characterize a small molecule (C22) that impairs eggshell integrity and disrupts early embryogenesis to determine its applicability as a potential FUdR alternative. We find that C22 prevents egg hatching in a concentration dependent manner. However, it extends the lifespan of wild type worms and can induce FMO-2, a longevity regulating enzyme downstream of dietary restriction. Our results suggest that C22 is unlikely to be widely useful as an alternative to FUdR but its mechanism for lifespan extension may be worth further investigation

Genetic interaction with temperature is an important determinant of nematode longevity

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140048/1/acel12658_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/140048/2/acel12658.pd

Towards understanding the traits contributing to performance of pearl millet open-pollinated varieties in phosphorus-limited environments of West Africa

Aims Pearl millet [Pennisetum glaucum (L.) R. Br.] open-pollinated varieties, which are the predominant cultivars, have never been systematically evaluated for adaptation to low-soil phosphorus (P), a major constraint on pearl millet production in West Africa (WA). Methods We evaluated grain yield (GY), flowering time (FLO), harvest index (HI), and residual grain yields (RGY) of 102 open-pollinated varieties from WA under low-P (−P) and high-P (+P) field conditions in six environments of WA. In addition, PE-related traits of the varieties were evaluated at early growth stage in a pot experiment. Results Significant genetic variation was observed for GY, FLO, HI and PE-related traits. P-efficient varieties had higher yield under −P conditions. Varietal performance under −P varied across environments depending on FLO, relative flowering delay under −P (FD) and RGY measured in the field. Low-P-susceptible varieties had higher FLO, lower HI than low-P-tolerant varieties. Response to direct selection under −P field conditions was 20.1 g m−2, whereas indirect selection response under +P was 16.3 g m−2. Conclusions Selection under −P field conditions while taking into account seasonal variations for FLO, FD and PE is expected to be important for improving GY specifically targeting −P environments in WA

Nrf2 Signaling, a Mechanism for Cellular Stress Resistance in Long-Lived Mice▿

Transcriptional regulation of the antioxidant response element (ARE) by Nrf2 is important for the cellular adaptive response to toxic insults. New data show that primary skin-derived fibroblasts from the long-lived Snell dwarf mutant mouse, previously shown to be resistant to many toxic stresses, have elevated levels of Nrf2 and of multiple Nrf2-sensitive ARE genes. Dwarf-derived fibroblasts exhibit many of the traits associated with enhanced activity of Nrf2/ARE, including higher levels of glutathione and resistance to plasma membrane lipid peroxidation. Treatment of control cells with arsenite, an inducer of Nrf2 activity, increases their resistance to paraquat, hydrogen peroxide, cadmium, and UV light, rendering these cells as stress resistant as untreated cells from dwarf mice. Furthermore, mRNA levels for some Nrf2-sensitive genes are elevated in at least some tissues of Snell dwarf mice, suggesting that the phenotypes observed in culture may be mirrored in vivo. Augmented activity of Nrf2 and ARE-responsive genes may coordinate many of the stress resistance traits seen in cells from these long-lived mutant mice

Dear Enemies Elicit Lower Androgen Responses to Territorial Challenges than Unfamiliar Intruders in a Cichlid Fish

In many territorial species androgen hormones are known to increase in response to territorial intrusions as a way to adjust the expression of androgen-dependent behaviour to social challenges. The dear enemy effect has also been described in territorial species and posits that resident individuals show a more aggressive response to intrusions by strangers than by other territorial neighbours. Therefore, we hypothesized that the dear enemy effect may also modulate the androgen response to a territorial intrusion. Here we tested this hypothesis in male cichlid fish (Mozambique tilapia, Oreochromis mossambicus) using a paradigm of four repeated territorial intrusions, either by the same neighbour or by four different unfamiliar intruders. Neighbour intruders elicited lower aggression and a weaker androgen response than strangers on the first intrusion of the experiment. With repeated intrusions, the agonistic behaviour of the resident males against familiar intruders was similar to that displayed towards strangers. By the fourth intrusion the androgen response was significantly reduced and there was no longer a difference between the responses to the two types of intruders. These results suggest that the dear enemy effect modulates the androgen response to territorial intrusions and that repeated intrusions lead to a habituation of the androgen response

Fmo induction as a tool to screen for pro-longevity drugs

Dietary restriction (DR) and hypoxia (low oxygen) extend lifespan in Caenorhabditis elegans through the induction of a convergent downstream longevity gene, fmo-2. Flavin-containing monooxygenases (FMOs) are highly conserved xenobiotic-metabolizing enzymes with a clear role in promoting longevity in nematodes and a plausible similar role in mammals. This makes them an attractive potential target of small molecule drugs to stimulate the health-promoting effects of longevity pathways. Here, we utilize an fmo-2 fluorescent transcriptional reporter in C. elegans to screen a set of 80 compounds previously shown to improve stress resistance in mouse fibroblasts. Our data show that 19 compounds significantly induce fmo-2, and 10 of the compounds induce fmo-2 more than twofold. Interestingly, 9 of the 10 high fmo-2 inducers also extend lifespan in C. elegans. Two of these drugs, mitochondrial respiration chain complex inhibitors, interact with the hypoxia pathway to induce fmo-2, whereas two dopamine receptor type 2 (DRD2) antagonists interact with the DR pathway to induce fmo-2, indicating that dopamine signaling is involved in DR-mediated fmo-2 induction. Together, our data identify nine drugs that each (1) increase stress resistance in mouse fibroblasts, (2) induce fmo-2 in C. elegans, and (3) extend nematode lifespan, some through known longevity pathways. These results define fmo-2 induction as a viable approach to identifying and understanding mechanisms of putative longevity compounds.This work was funded by the Glenn Foundation for Medical Research and NIH grant R01AG075061 to S.F.L12 month embargo; first published 24 May 2024This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]