In a study published in 2015, Bansel et al. found that long-lived C. elegans mutants exhibited a higher proportion of life in an unhealthy state compared to non-mutants. In their 2017 publication, Rollins et al. sought to better understand the relationship between lifespan and quality of life in C. elegans mutants. The authors used two models to assess health span in short-lived mutants: one focused on age-dependent factors such as locomotion, maximum bending amplitude, and thermo-tolerance; the other examined the effects of extrinsic forces over time, including accumulation of autofluorescence and pharyngeal pumping.

To track the worms and obtain data on size and behavior including speed of locomotion and bending angle, the researchers utilized WormLab® software. They found that short-lived mutants spent less time in a healthy state compared to non-mutants, when locomotion markers were used for the evaluation.   Unexpectedly, however, short-lived mutants exhibited thermo-tolerance for a longer percentage of life span than wild-type worms, suggesting that these mutants may have an advantage in this particular measure of health span.

The authors propose a new metric that combines survival rate and health performance to more accurately score health, taking into account both age-dependent and time-dependent factors. This approach could help to better understand the relationship between lifespan and quality of life in model organisms and could have implications for future research on aging and longevity.

In conclusion, the study of short-lived C. elegans mutants provides valuable insights into the relationship between life span and quality of life. The use of two models to assess health and the proposal of a new metric to score health highlight the complexity of this relationship and the need for further research to fully understand it. As we continue to strive for longer, healthier lives, the use of model organisms like C. elegans will undoubtedly remain essential to this research as we aim to promote healthy aging and unlock the secrets of aging.

Learn more about the WormLab software

Reference:

Rollins, J. A., Howard, A. C., Dobbins, S. K., Washburn, E. H., & Rogers, A. N. (2017). Assessing health span in Caenorhabditis elegans: Lessons from short-lived mutants. The Journals of Gerontology: Series A, 72(4), 473–480. https://doi.org/10.1093/gerona/glw248

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Seeking novel targets with the potential to move the needle on obesity-linked cardiometabolic disorders, a research team led by Marc Prentki and S. R. Murthy Madirajua at the Université de Montréal discovered glycerol-3-phosphate phosphatase (G3PP) in mammalian cells, an enzyme involved in the glycerolipid/fatty acid (GL/FA) cycle. This cycle is comprised of lipogenesis and lipolysis segments; it produces building blocks for complex lipids, such as triglycerides, promotes thermogenesis, and generates signaling molecules involved in many biological processes, including insulin secretion and action. Dysregulation of the GL/FA cycle is associated with metabolic and age-related diseases, including obesity and type 2 diabetes.

The MBF WormLab^® software and imaging system was an integral part of this research. “Using Wormlab, a user-friendly and powerful software, we were able to track and analyze the locomotion behavior of a large pool of aging C. elegans nematodes. Wormlab enabled the quick and efficient analysis of recorded videos and the accurate quantification of multiple parameters including body bending, speed, worm length and others.” Elite Possik, PhD.

The authors explain that, prior to their discovery in 2016, mammals were thought to lack an enzyme capable of converting glycerol-3-phosphate (Gro3P) to glycerol. But according to the paper, G3PP can do just that, effectively bypassing lipolysis, which was previously thought to be the only source of glycerol in mammals. Their earlier research suggests a role for G3PP in “the control of glycolysis, gluconeogenesis, cellular redox, and energy production” in conditions of glucose excess.

Fig: 1 pgph-2 overexpression improves health span and decreases fat content.	Fig 2: pgph-2 overexpression increases lifespan under excess glucose and reduces glucose-induced fat deposition

In this study, published in Nature Communications, the researchers used the model organism C. elegans to identify the biological functions of G3PP. First, they identified three homologs of mammalian G3PP in C. elegans based on protein sequence identity to the human enzyme; they’re named phosphoglycolate phosphatase homologs (PGPH), pgph-1, pgph-2, and pgph-3. Using triple pgph deletion mutants that lack all three homologs, the researchers established that the worm PGPH isoenzymes mimic G3PP in vivo under normal physiological conditions. They found no phenotypic defects in pharyngeal pumping, egg laying, brood size, or swimming behaviors, but did find that triple mutants had increased fat deposition in the context of normal levels of glycolytic metabolites such as, Krebs cycle intermediates, and DNA building and repair compounds. Using RNAi knockdown and expression analyses of genes known to drive lipogenesis in C. elegans, the team showed that the increased fat accumulation in triple mutants was due to an increase in the lipogenesis arm of the GL/FA cycle.

Response to hyperosmotic stress is of particular interest; glycerol is an important component of adaptation in many organisms. The researchers found that pgph genes were strongly induced in high-salt or high-glucose conditions. Deletion mutants were found to be significantly less able to tolerate these conditions compared to control worms. Further experiments demonstrated that both pgph gene expression and glycerol production increased when worms were exposed to 2% glucose, and loss of PGPH enzymes suppressed glucose-induced glycerol production. This supports the premise that PGPH enzyme activity “is required for resistance to hyperosmotic stress” from salt or excess glucose by increasing glycerol production.

Excess glucose has been shown to shorten the C. elegans lifespan. The research team extensively examined the roles and mechanisms of PGPH isoenzymes in susceptibility and resistance to glucotoxicity. The MBF Bioscience WormLab Imaging System was used to conduct lifespan and glucose toxicity assays. WormLab software enabled the scientists to film and analyze worms’ movement behaviors, which serve as an index of healthy aging.

Using pgph deletion mutants and RNAi knockdown, loss of PGPH activity shortened worm lifespan and healthspan in normal and high-glucose environments. The team then evaluated pgph-2 overexpression and found that it protected worms from glucose-induced toxicity, improved healthspan, decreased fat content, and extended median lifespan in glucose-rich conditions. Importantly, they showed that the decreased fat content was not due to decreased calorie intake and that the extended healthspan they observed was not at the expense of energy expended for reproduction. Further experiments with pgph-2 overexpressing worms revealed that, in the presence of glucose, worms maintained better locomotion behaviors with age. Specifically, they exhibited more body bends per second and higher locomotion and peristaltic speed. pgph-2 overexpressing animals’ fat content was lower than control worms in glucose-excess conditions and was comparable with that of control worms grown in normal growth medium; this correlated with decreased expression of lipogenesis genes in the pgph-2 overexpressors.

This study characterizes a key enzyme and a distinct biochemical pathway that mimics some of the beneficial effects of calorie restriction, without the drawbacks of fertility changes and the difficulty of maintaining reduced caloric intake. They conclude that G3PP activation has potential as a novel approach for prevention and treatment of diseases that occur from nutritional excess, such as obesity, diabetes, and cardiovascular disease.

Possik, E., Schmitt, C., Al-Mass, A. et al. Phosphoglycolate phosphatase homologs act as glycerol-3-phosphate phosphatase to control stress and healthspan in C. elegans. Nat Commun 13, 177 (2022). https://doi.org/10.1038/s41467-021-27803-6

Learn more about the WormLab Imaging System, a complete, scalable solution for automated imaging and quantitative analysis of behavior in C. elegans and other nematodes.

Stand-alone WormLab software is also available for imaging, tracking, and behavior analysis in C. elegans and other worms. Learn more about WormLab software here.

The post Characterizing a novel target to combat obesity appeared first on MBF Bioscience.

We continue our history of innovation and invention as the U.S. Patent and Trademark Office awards us two patents. The first is for WormLab – our unique worm tracking software that gives researchers an enormous amount of behavioral data about a single worm or multiple worms, even as they go through omega bends, reversals, and entanglements. The second is for our radial shock wave technology that improves antibody penetration and reduces the time for antibody incubation and fixation periods.

WormLab is commercially available, while our shock wave technology is in development.

+ Learn more about WormLab

+ Read the WormLab patent

+ Read the shock wave patent

The post MBF Bioscience Awarded Two Patents in 2016 appeared first on MBF Bioscience.

Explosions can tear apart buildings, send shrapnel flying, and hurtle humans into the air. But explosions also cause damage in ways that aren’t as visually apparent. Scientists say the force of a blast can cause brain damage, but questions linger about how the symptoms that emerge after a blast-induced traumatic brain injury are connected to the initial trauma.

In their quest to learn more about how symptoms emerge after a traumatic blast, researchers at the Ludwig-Maximilians University of Munich, in Munich, Germany have developed an animal model of blast-related mild traumatic brain injury (br-mTBI) using C. elegans – a popular model organism alternative to vertebrate animals.

In their study, published in Frontiers in Behavioral Neuroscience, the research team used WormLab to analyze thousands of worms. They found that shockwaves either slowed the worms’ movements or rendered them paralyzed. Symptoms played out in a dose-dependent manner, meaning that worms exposed to a higher number of shockwaves displayed a higher severity of symptoms.

To create their model, the scientists set up a system where C. elegans contained in a liquid medium were exposed to shock waves from a therapeutic shock wave device. These shock waves share characteristics with the types of shock waves that might induce mTBI in humans – the types of shock waves soldiers experience in war zones.

Each sample of worms was exposed to a certain number of shock waves ranging from zero to 500, then transferred to agar plates for analysis with WormLab, MBF Bioscience’s system for imaging, tracking, and analyzing C. elegans. Using a dissecting microscope equipped with a digital camera and WormLab’s built-in video capture function, the researchers captured a series of one-minute videos of the worms in motion. By analyzing these videos with WormLab, the scientists were able to calculate each worm’s average speed, and count the number of paralyzed worms.

“Given the high variability in C. elegans behavior we observed, generating a large sample size was crucial to our study,” said first author Nicholas Angstman. “WormLab made this easy, allowing us to capture hundreds of videos and generate useful behavioral data on thousands of worms in the quick manner we needed.”

When mTBI occurs from the shock waves of a blast (as opposed to a blunt force injury sustained from impact from other objects because of the blast), there are two parts of the blast that could cause injury – the high positive pressure from the first part of the blast wave, and the cavitation that occurs as a result of the vacuum that forms from the initial force of the blast.

Since cavitation is thought to be a substantial factor in blast-induced mTBI, the researchers set up an experimental group of C. elegans in polyvinyl alcohol – a liquid solution known to reduce cavitation. This allowed them to study the effects of a blast on C. elegans in the absence of cavitation.

What they saw was that these worms, though slowed, demonstrated a higher average speed than the control worms, which were exposed to shock waves in the liquid medium in which they were bred, as well as a decreased amount of paralyzed worms compared to controls. These observations led the researchers to conclude that while cavitation contributes significantly to the damaging effects of shock waves on C. elegans, primary blast waves are also injurious.

The scientists also observed that worms exposed to the same conditions displayed a large variability between individuals. They also saw that worms were able to recover from paralysis and reduced speed after a certain amount of time.

“The possibility to investigate br-mTBI at a simple, high-throughput level makes C. elegans a useful model organism in the attempt to connect the bridge between cause and effect in br-mTBI.,” the authors say in their paper.

Angstman, N., Kiessling, M., Frank, H.G., and Schmitz, C. (2015) High interindividual variability in dose-dependent reduction in speed of movement after exposing C. elegans to shock waves. Front Behav Neurosci. 2015; 9: 12. doi: 10.3389/fnbeh.2015.00012

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Smokers aren’t only hurting themselves, they’re also hurting their children and grandchildren. So says a study published last month in the EXCLI Journal.

Scientists at East Carolina University, in Greenville, North Carolina saw unusual behavior in C. elegans roundworms exposed to nicotine at an early stage of development. But that’s not all – the researchers also witnessed abnormal behavior and withdrawal symptoms in subsequent generations of worms even though these groups were not directly exposed to nicotine.

In their study, the researchers focused on three generations of C. elegans, which, because of their similarity to humans on a cellular, neural, and developmental level, make an excellent model organism for biological study. The first generation, the only one directly exposed to nicotine, was divided into three groups: the control group (no nicotine), the low dose group (20 μm); and the high dose group (20 mM).

Using WormLab to analyze videos of each of the nine groups of worms, the researchers measured key behaviors like omega bends, reversals, and backward and forward movements. Armed with a set of data points generated by the software, they discovered that the effect of nicotine on locomotion, dynamic body movements, and speed has a transgenerational impact in C. elegans.

One of the most significant differences between the three treatment groups was the high number of omega bends observed in the high-dose group. Though this behavior decreased with subsequent generations, the levels remained much higher than in control and low-dose populations.

Other observations, like vigorous bending and faster forward and backward speeds in both the low-dose and high-dose third generation groups compared to controls, led the scientists to speculate that speed may be a symptom of withdrawal.

“The hyperactive behavior can be reflective of craving or uneasiness in worms as they are no longer getting their addicting and satisfying nicotine dose,” they say in their paper.

But they also say that nicotine’s effects lessen with subsequent generations, explaining that second and third generations moved more, displaying less of the “paralyzed” behavior they saw in the first generation nicotine-treated worms.

These changes in normal behavior, the researchers say, are the result of the drug’s affect on specific neurons such as the AVA neuron, which is involved in reversals, and the SMD, RIV, and SMB, neurons that play a role in the dynamics of omega bends.

“Our study is the first to reveal that nicotine addiction is heritable using C. elegans as a model organism,” the authors say. “These results underscored the sensitivity of early development stages, with hope to spread more awareness to encourage the avoidance of nicotine exposure, especially at a young age.”

Taki, A., Faten, Pan, Xiaoping, & Zhang, Baohong. (2013). Nicotine Exposure Caused Significant Transgenerational Heritable Behavioral Changes in Caenorhabditis Elegans. EXCLI journal, 1611-2156. doi: http://www.excli.de/vol12/Zhang_10092013_proof.pdf

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WormLab is already contributing to a variety of research projects from the study of neurodegeneration at Johns Hopkins, to research on neural circuit function at UMass, neurotransmitter transporters at Vanderbilt University, and explorations into how the brain controls growth and fat metabolism at the University of Nevada, Reno. Why? WormLab is intuitive, fast, and yields an astounding amount of data very quickly.

Try it with your own data by downloading a 15-day free trial from our website to find out if WormLab is the right tool for you.

The post With WormLab, Worm Detection and Tracking Has Never Been So Simple – Find Out With a Free Trial. appeared first on MBF Bioscience.

There’s a groundbreaking new tool in town. It’s called WormLab, and it’s going to revolutionize the way scientists analyze the behavior of C. elegans – tiny worms used as model organisms in research studies.

WormLab helps scientists analyze the locomotion and behavior of C. elegans by providing precise information and analyses about their speed, direction, position, and wavelength. The software can track multiple worms as they interact and become entangled, giving scientists more data than what they would find in other software options.

“WormLab provides a user independent way to objectively measure phenotypes. This is a significant advance for quantitative phenotyping packaged in a user-friendly platform,” said University of Washington Research Biologist Dr. Brian Kraemer.

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