scholarly journals CAMKII and Calcineurin regulate the lifespan of Caenorhabditis elegans through the FOXO transcription factor DAF-16

eLife ◽  
2013 ◽  
Vol 2 ◽  
Author(s):  
Li Tao ◽  
Qi Xie ◽  
Yue-He Ding ◽  
Shang-Tong Li ◽  
Shengyi Peng ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Nuclear Localization ◽  
Insulin Signaling ◽  
Mammalian Cells ◽  
Nuclear Translocation ◽  
Type Ii ◽  
Wild Type ◽  
C Elegans ◽  
Foxo Transcription Factors ◽  
Lifespan Regulation

The insulin-like signaling pathway maintains a relatively short wild-type lifespan in Caenorhabditis elegans by phosphorylating and inactivating DAF-16, the ortholog of the FOXO transcription factors of mammalian cells. DAF-16 is phosphorylated by the AKT kinases, preventing its nuclear translocation. Calcineurin (PP2B phosphatase) also limits the lifespan of C. elegans, but the mechanism through which it does so is unknown. Herein, we show that TAX-6•CNB-1 and UNC-43, the C. elegans Calcineurin and Ca2+/calmodulin-dependent kinase type II (CAMKII) orthologs, respectively, also regulate lifespan through DAF-16. Moreover, UNC-43 regulates DAF-16 in response to various stress conditions, including starvation, heat or oxidative stress, and cooperatively contributes to lifespan regulation by insulin signaling. However, unlike insulin signaling, UNC-43 phosphorylates and activates DAF-16, thus promoting its nuclear localization. The phosphorylation of DAF-16 at S286 by UNC-43 is removed by TAX-6•CNB-1, leading to DAF-16 inactivation. Mammalian FOXO3 is also regulated by CAMKIIA and Calcineurin.

scholarly journals Electrophysiological Measures of Aging Pharynx Function in C. elegans Reveal Enhanced Organ Functionality in Older, Long-lived Mutants

2017 ◽  
Vol 74 (8) ◽  
pp. 1173-1179 ◽  
Author(s):  
Joshua Coulter Russell ◽  
Nikolay Burnaevskiy ◽  
Bridget Ma ◽  
Miguel Arenas Mailig ◽  
Franklin Faust ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Heat Shock ◽  
Life Span ◽  
Insulin Signaling ◽  
Model System ◽  
Wild Type ◽  
Organ Function ◽  
C Elegans ◽  
Age Related ◽  
The Relationship

Abstract The function of the pharynx, an organ in the model system Caenorhabditis elegans, has been correlated with life span and motility (another measure of health) since 1980. In this study, in order to further understand the relationship between organ function and life span, we measured the age-related decline of the pharynx using an electrophysiological approach. We measured and analyzed electropharyngeograms (EPG) of wild type animals, short-lived hsf-1 mutants, and long-lived animals with genetically decreased insulin signaling or increased heat shock pathway signaling; we recorded a total of 2,478 EPGs from 1,374 individuals. As expected, the long-lived daf-2(e1370) and hsf-1OE(uthIs235) animals maintained pharynx function relatively closer to the youthful state during aging, whereas the hsf-1(sy441) and wild type animals’ pharynx function deviated significantly further from the youthful state at advanced age. Measures of the amount of variation in organ function can act as biomarkers of youthful physiology as well. Intriguingly, the long-lived animals had greater variation in the duration of pharynx contraction at older ages.

The Effect of Mianserin on Lifespan of Caenorhabditis elegans is Abolished by Glucose

2021 ◽  
Vol 13 ◽  
Author(s):  
Abdullah Almotayri ◽  
Jency Thomas ◽  
Mihiri Munasinghe ◽  
Markandeya Jois
Keyword(s):  
Caenorhabditis Elegans ◽  
Scaffolding Protein ◽  
Lifespan Extension ◽  
Wild Type ◽  
E Coli ◽  
C Elegans ◽  
Risk Of Death ◽  
Increased Risk ◽  
Antidepressant Use ◽  
Extension Effect

Background: The antidepressant mianserin has been shown to extend the lifespan of Caenorhabditis elegans (C. elegans), a well-established model organism used in aging research. The extension of lifespan in C. elegans was shown to be dependent on increased expression of the scaffolding protein (ANK3/unc-44). In contrast, antidepressant use in humans is associated with an increased risk of death. The C. elegans in the laboratory are fed Escherichia coli (E. coli), a diet high in protein and low in carbohydrate, whereas a typical human diet is high in carbohydrates. We hypothesized that dietary carbohydrates might mitigate the lifespan-extension effect of mianserin. Objective: To investigate the effect of glucose added to the diet of C. elegans on the lifespan-extension effect of mianserin. Methods: Wild-type Bristol N2 and ANK3/unc-44 inactivating mutants were cultured on agar plates containing nematode growth medium and fed E. coli. Treatment groups included (C) control, (M50) 50 μM mianserin, (G) 73 mM glucose, and (M50G) 50 μM mianserin and 73 mM glucose. Lifespan was determined by monitoring the worms until they died. Statistical analysis was performed using the Kaplan-Meier version of the log-rank test. Results: Mianserin treatment resulted in a 12% increase in lifespan (P<0.05) of wild-type Bristol N2 worms but reduced lifespan by 6% in ANK3/unc-44 mutants, consistent with previous research. The addition of glucose to the diet reduced the lifespan of both strains of worms and abolished the lifespan-extension by mianserin. Conclusion: The addition of glucose to the diet of C. elegans abolishes the lifespan-extension effects of mianserin.

scholarly journals Sperm Competition in the Absence of Fertilization in Caenorhabditis elegans

Genetics ◽  
1999 ◽  
Vol 152 (1) ◽  
pp. 201-208 ◽  
Author(s):  
Andrew Singson ◽  
Katherine L Hill ◽  
Steven W L’Hernault
Keyword(s):  
Caenorhabditis Elegans ◽  
Sperm Competition ◽  
Sperm Function ◽  
Sperm Precedence ◽  
Wild Type ◽  
Nematode Caenorhabditis Elegans ◽  
C Elegans ◽  
Normal Sperm ◽  
Self Fertilization ◽  
Competition Assays

Abstract Hermaphrodite self-fertilization is the primary mode of reproduction in the nematode Caenorhabditis elegans. However, when a hermaphrodite is crossed with a male, nearly all of the oocytes are fertilized by male-derived sperm. This sperm precedence during reproduction is due to the competitive superiority of male-derived sperm and results in a functional suppression of hermaphrodite self-fertility. In this study, mutant males that inseminate fertilization-defective sperm were used to reveal that sperm competition within a hermaphrodite does not require successful fertilization. However, sperm competition does require normal sperm motility. Additionally, sperm competition is not an absolute process because oocytes not fertilized by male-derived sperm can sometimes be fertilized by hermaphrodite-derived sperm. These results indicate that outcrossed progeny result from a wild-type cross because male-derived sperm are competitively superior and hermaphrodite-derived sperm become unavailable to oocytes. The sperm competition assays described in this study will be useful in further classifying the large number of currently identified mutations that alter sperm function and development in C. elegans.

Streblus asper Lour. exerts MAPK and SKN-1 mediated anti-aging, anti-photoaging activities and imparts neuroprotection by ameliorating Aβ in Caenorhabditis elegans

2021 ◽  
pp. 1-17
Author(s):  
Mani Iyer Prasanth ◽  
James Michael Brimson ◽  
Dicson Sheeja Malar ◽  
Anchalee Prasansuklab ◽  
Tewin Tencomnao
Keyword(s):  
Oxidative Stress ◽  
Caenorhabditis Elegans ◽  
Stress Resistance ◽  
Vital Role ◽  
Transgenic Strain ◽  
Wild Type ◽  
Neuroprotective Effects ◽  
C Elegans ◽  
Streblus Asper

BACKGROUND: Streblus asper Lour., has been reported to have anti-aging and neuroprotective efficacies in vitro. OBJECTIVE: To analyze the anti-aging, anti-photoaging and neuroprotective efficacies of S. asper in Caenorhabditis elegans. METHODS: C. elegans (wild type and gene specific mutants) were treated with S. asper extract and analyzed for lifespan and other health benefits through physiological assays, fluorescence microscopy, qPCR and Western blot. RESULTS: The plant extract was found to increase the lifespan, reduce the accumulation of lipofuscin and modulate the expression of candidate genes. It could extend the lifespan of both daf-16 and daf-2 mutants whereas the pmk-1 mutant showed no effect. The activation of skn-1 was observed in skn-1::GFP transgenic strain and in qPCR expression. Further, the extract can extend the lifespan of UV-A exposed nematodes along with reducing ROS levels. Additionally, the extract also extends lifespan and reduces paralysis in Aβ transgenic strain, apart from reducing Aβ expression. CONCLUSIONS: S. asper was able to extend the lifespan and healthspan of C. elegans which was independent of DAF-16 pathway but dependent on SKN-1 and MAPK which could play a vital role in eliciting the anti-aging, anti-photoaging and neuroprotective effects, as the extract could impart oxidative stress resistance and neuroprotection.

scholarly journals Genetic, Behavioral and Environmental Determinants of Male Longevity in Caenorhabditis elegans

Genetics ◽  
2000 ◽  
Vol 154 (4) ◽  
pp. 1597-1610 ◽  
Author(s):  
David Gems ◽  
Donald L Riddle
Keyword(s):  
Caenorhabditis Elegans ◽  
Life Span ◽  
Wild Type ◽  
Neuronal Function ◽  
Nematode Caenorhabditis Elegans ◽  
Wild Isolate ◽  
Young Males ◽  
C Elegans ◽  
Single Sex ◽  
Solitary Males

Abstract Males of the nematode Caenorhabditis elegans are shorter lived than hermaphrodites when maintained in single-sex groups. We observed that groups of young males form clumps and that solitary males live longer, indicating that male-male interactions reduce life span. By contrast, grouped or isolated hermaphrodites exhibited the same longevity. In one wild isolate of C. elegans, AB2, there was evidence of copulation between males. Nine uncoordinated (unc) mutations were used to block clumping behavior. These mutations had little effect on hermaphrodite life span in most cases, yet many increased male longevity even beyond that of solitary wild-type males. In one case, the neuronal function mutant unc-64(e246), hermaphrodite life span was also increased by up to 60%. The longevity of unc-4(e120), unc-13(e51), and unc-32(e189) males exceeded that of hermaphrodites by 70–120%. This difference appears to reflect a difference in sex-specific life span potential revealed in the absence of male behavior that is detrimental to survival. The greater longevity of males appears not to be affected by daf-2, but is influenced by daf-16. In the absence of male-male interactions, median (but not maximum) male life span was variable. This variability was reduced when dead bacteria were used as food. Maintenance on dead bacteria extended both male and hermaphrodite longevity.

scholarly journals Goα Regulates Volatile Anesthetic Action in Caenorhabditis elegans

Genetics ◽  
2001 ◽  
Vol 158 (2) ◽  
pp. 643-655 ◽  
Author(s):  
Bruno van Swinderen ◽  
Laura B Metz ◽  
Laynie D Shebester ◽  
Jane E Mendel ◽  
Paul W Sternberg ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Novel Mutation ◽  
Volatile Anesthetic ◽  
Loss Of Function ◽  
Wild Type ◽  
Α Subunit ◽  
C Elegans ◽  
Missense Mutant ◽  
Anesthetic Action ◽  
Mutant Phenotypes

Abstract To identify genes controlling volatile anesthetic (VA) action, we have screened through existing Caenorhabditis elegans mutants and found that strains with a reduction in Go signaling are VA resistant. Loss-of-function mutants of the gene goa-1, which codes for the α-subunit of Go, have EC50s for the VA isoflurane of 1.7- to 2.4-fold that of wild type. Strains overexpressing egl-10, which codes for an RGS protein negatively regulating goa-1, are also isoflurane resistant. However, sensitivity to halothane, a structurally distinct VA, is differentially affected by Go pathway mutants. The RGS overexpressing strains, a goa-1 missense mutant found to carry a novel mutation near the GTP-binding domain, and eat-16(rf) mutants, which suppress goa-1(gf) mutations, are all halothane resistant; goa-1(null) mutants have wild-type sensitivities. Double mutant strains carrying mutations in both goa-1 and unc-64, which codes for a neuronal syntaxin previously found to regulate VA sensitivity, show that the syntaxin mutant phenotypes depend in part on goa-1 expression. Pharmacological assays using the cholinesterase inhibitor aldicarb suggest that VAs and GOA-1 similarly downregulate cholinergic neurotransmitter release in C. elegans. Thus, the mechanism of action of VAs in C. elegans is regulated by Goα, and presynaptic Goα-effectors are candidate VA molecular targets.

Identification Of A Novel Gene Altered In The RQ1 Mutant Strain Affecting Motor Axon Migration In Caenorhabditis Elegans

2021 ◽  
Author(s):  
Haider Z. Naqvi
Keyword(s):  
Caenorhabditis Elegans ◽  
Axon Guidance ◽  
Motor Neurons ◽  
Genetic Background ◽  
Germ Line ◽  
Strong Indication ◽  
Wild Type ◽  
C Elegans ◽  
Novel Gene ◽  
Mutation Region

Novel genetic enhancer screens were conducted targeting mutants involved in the guidance of axons of the DA and DB classes of motor neurons in C. elegans. These mutations are expected in genes that function in parallel to the unc-g/Netrin pathway. The screen was conducted in an unc-5(e53) genetic background and enhancers of the axon guidance defects caused by the absence of UNC-5 were identified. Three mutants were previously identified in the screen called rq1, rq2 and rq3 and two additional mutants called H2-4 and M1-3, were isolated in this study. In order to identify the gene affected by the rq1 mutation, wild-type copies of genes in the mapped rq1 mutation region were injected into the mutants to rescue the phenotypic defects. This is a strong indication that the gene of interest is a novel gene called H04D03.1. Promising results indicate that the H04D03.1 protein also works in germ-line apoptosis.

scholarly journals Isolation, characterization and epistasis of fluoride-resistant mutants of Caenorhabditis elegans.

Genetics ◽  
1994 ◽  
Vol 136 (1) ◽  
pp. 145-154
Author(s):  
I Katsura ◽  
K Kondo ◽  
T Amano ◽  
T Ishihara ◽  
M Kawakami
Keyword(s):  
Caenorhabditis Elegans ◽  
Brood Size ◽  
Normal Growth ◽  
Fluoride Ion ◽  
Wild Type ◽  
Signal Transduction System ◽  
Nematode Caenorhabditis Elegans ◽  
C Elegans ◽  
Class 1 ◽  
Resistant Mutants

Abstract We have isolated 13 fluoride-resistant mutants of the nematode Caenorhabditis elegans. All the mutations are recessive and mapped to five genes. Mutants in three of the genes (class 1 genes: flr-1 X, flr-3 IV, and flr-4 X) are resistant to 400 micrograms/ml NaF. Furthermore, they grow twice as slowly as and have smaller brood size than wild-type worms even in the absence of fluoride ion. In contrast, mutants in the other two genes (class 2 genes: flr-2 V and flr-5 V) are only partially resistant to 400 micrograms/ml NaF, and they have almost normal growth rates and brood sizes in the absence of fluoride ion. Studies on the phenotypes of double mutants showed that class 2 mutations are epistatic to class 1 mutations concerning growth rate and brood size but hypostatic with respect to fluoride resistance. We propose two models that can explain the epistasis. Since fluoride ion depletes calcium ion, inhibits some protein phosphatases and activates trimeric G-proteins, studies on these mutants may lead to discovery of a new signal transduction system that controls the growth of C. elegans.

scholarly journals Temporal Transcriptomics of Gut Escherichia coli in Caenorhabditis elegans Models of Aging

2021 ◽  
Author(s):  
Joshua D. Brycki ◽  
Jeremy R. Chen See ◽  
Gillian R. Letson ◽  
Cade S. Emlet ◽  
Lavinia V. Unverdorben ◽  
...  
Keyword(s):  
Gene Expression ◽  
Escherichia Coli ◽  
Caenorhabditis Elegans ◽  
Life Span ◽  
Wild Type ◽  
Health Span ◽  
Content Type ◽  
C Elegans ◽  
Evolutionarily Conserved

Previous research has reported effects of the microbiome on health span and life span of Caenorhabditis elegans , including interactions with evolutionarily conserved pathways in humans. We build on this literature by reporting the gene expression of Escherichia coli OP50 in wild-type (N2) and three long-lived mutants of C. elegans .

scholarly journals H3K9me2 protects lifespan against the transgenerational burden of germline transcription in C. elegans

2019 ◽  
Author(s):  
Teresa W. Lee ◽  
Heidi S. David ◽  
Amanda K. Engstrom ◽  
Brandon S. Carpenter ◽  
David J. Katz
Keyword(s):  
Caenorhabditis Elegans ◽  
Histone H3 ◽  
Complex Trait ◽  
Wild Type ◽  
C Elegans ◽  
Germline Transcription ◽  
Active Transcription

ABSTRACTDuring active transcription, the COMPASS complex methylates histone H3 at lysine 4 (H3K4me). In Caenorhabditis elegans, mutations in COMPASS subunits, including WDR-5, extend lifespan and enable the inheritance of increased lifespan in wild-type descendants. Here we show that the increased lifespan of wdr-5 mutants is itself a transgenerational trait that manifests after eighteen generations and correlates with changes in the heterochromatin factor H3K9me2. Additionally, we find that wdr-5 mutant longevity and its inheritance requires the H3K9me2 methyltransferase MET-2 and can be recapitulated by a mutation in the putative H3K9me2 demethylase JHDM-1. These data suggest that lifespan is constrained by reduced H3K9me2 due to transcription-coupled H3K4me. wdr-5 mutants alleviate this burden, extending lifespan and enabling the inheritance of increased lifespan. Thus, H3K9me2 functions in the epigenetic establishment and inheritance of a complex trait. Based on this model, we propose that lifespan is limited by the germline in part because germline transcription reduces heterochromatin.

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