Aging  

Researchers have dramatically increased the lifespan of the common fruit fly by activating a newly-discovered gene responsible for eliminating unhealthy cells.

Researchers have managed to increase the lifespan of flies significantly. To do this, they have activated a gene that destroys unhealthy cells. The results of the study show by new possibilities of how to slow aging in humans.

The new research has been published in the journal Cell.

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Biologists continue to try extend the life of people through the exploration of model organisms such as mice or flies. Under the leadership of Eduardo Moreno is researcher at the Institute of Cell Biology, University of Bern now possible to develop a new method for the life of flies extension.

"We reasoned that selecting the less affected cells and eliminating the damaged ones could be a good strategy to maintain tissue health and therefore delay aging and prolong lifespan."

This is based on the targeted selection of the best functioning cells.

"Our bodies are composed of trillions of cells," says Moreno. "As we age, accumulate in them due to overloading or external interference factors, such as UV radiation from the sun, getting more random defects." But these defects do not occur in all cells at the same time and with the same intensity as Moreno says: "Some cells are more affected than others.We reasoned that selecting the less affected cells and eliminating the damaged ones could be a good strategy to maintain tissue health and therefore delay aging and prolong lifespan."

To test their hypothesis, the researchers resorted back to the fruit fly Drosophila melanogaster. The first challenge was to find out what were the healthier cells in the organs of the fruit fly. Moreno's team discovered a gene that is activated in less healthy cells. They called the gene ahuizotl (azot) after a mythological Aztec creature selectively targeting fishing boats to protect the fish population of lakes, because the function of the gene was also to selectively target less healthy or less fit cells to protect the integrity and health of the organs like the brain or the gut.

Normally, there are two copies of this gene in a cell. By pasting-in a third copy, the scientists were able to sort out the healthier cells and nerve cells more efficiently. The result of this cellular "quality control", according to Moreno was "very exciting."

The treated flies showed a healthier tissue, aging more slowly and have a longer life. "Our flies lived an average of 50 to 60 percent longer than their other counterparts," says Christa Rhiner, co-author of the study.

However, the potential of these results goes beyond the creation of Methuselah flies, the researchers say, because the azote gene is also present in the human body, the selection of healthier, fitter cells in organs could, in the future, serve as a mechanism to slow aging.


SOURCE  University of Bern

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 Evolution  

Evolve and resequence (E&R) is a new approach for investigating the genomic responses to selection during experimental evolution. By using whole genome sequencing of pools of individuals (Pool-Seq), this method can identify select variables that, over the long term, control evolution.

Life implies change. And this holds true for genes as well. Organisms require a flexible genome in order to adapt to changes in the local environment. Christian Schlötterer and his team from the Institute for Population Genetics at the University of Veterinary Medicine, Vienna study the genomes of entire populations.

The scientists want to know why individuals differ from each other and how these differences are encoded in the DNA. In two review papers published in the journals Nature Reviews Genetics and Heredity, they discuss why DNA sequencing of entire groups can be an efficient and cost-effective way to answer these questions.

Overview of E&R studies - C Schlötterer, R Kofler, E Versace, R Tobler and S U Franssen / Heredity

"We are using this method to address a broad range of questions, ranging from the identification of genes which influence aging, or genes protecting against diseases and finally to understand the genetic changes which reduce the impact of climate change."

DNA analysis has become increasingly efficient and cost-effective since the human genome was first fully sequenced in the year 2001. Sequencing a complete genome, however, still costs around US$1,000. Sequencing the genetic code of hundreds of individuals would therefore be very expensive and time-consuming. In particular for non-human studies, researchers very quickly hit the limit of financial feasibility.

The solution to this problem is pool sequencing (Pool-Seq). Schlötterer and his team sequence entire groups of fruit flies (Drosophila melanogaster) at once instead of carrying out many individual sequencing reactions. While the resulting genetic information cannot be attributed to a single individual, the complete data set still provides important genetic information about the entire population.

In the two publications, Schlötterer and colleagues discuss the breadth of questions that can be addressed by Pool-Seq.

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In order to understand how organisms react to changes in the local environment, the genomes of entire populations can be analysed using Pool-Seq, before and after changed conditions. To do so, the researchers use the method of evolve and resequence (E&R).

After exposing the descendants of this group for several generations to a certain stress, such as high temperature, extreme cold or UV radiation, the evolved group is sequenced again. A comparison of the two data sets uncovers genes that have changed in response to the selective stress. The approach makes it possible, to filter out the genes that are involved in a darker pigmentation in response to UV radiation.

“Using this principle, we can perform evolution experiments at high speed. We are using this method to address a broad range of questions, ranging from the identification of genes which influence aging, or genes protecting against diseases and finally to understand the genetic changes which reduce the impact of climate change,” Schlötterer explains.

The evolve-and-resequence approach also makes it also possible to filter out the genes that regulate aging. This process involves selecting flies from a population, repeatedly over generations, that reach an especially old age.  Several generations later, the researchers then compare the genomes of the “Methuselah” flies with those from normally aging flies in order to extract the genes that are involved in the aging process. This method also works to locate genes that provide resistance against certain diseases.

Bioinformatician and co-author, Robert Kofler, explains: “We are dealing with genetic change processes and are searching for variations in the genomes. The variations can help us to understand how evolution works.”


SOURCE  University of Veterinary Medicine, Vienna

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 Medicine  

When we get sick it feels natural to try to hasten our recovery by getting some extra sleep. Researchers have found that this response has a definite purpose, in fruit flies: enhancing immune system response and recovery to infection.

When we get sick it feels natural to try to hasten our recovery by getting some extra sleep.  Now researchers from the Perelman School of Medicine at the University of Pennsylvania have found that this response has a definite purpose.  They found that in fruitflies sleep enhances immune system response and recovery to infection.

The findings appear online in two related papers in the journal Sleep, in advance of print editions in May and June.

Unexpectedly, the pre-infection, sleep-deprived flies had a better survival rate.

"It's an intuitive response to want to sleep when you get sick," notes Center for Sleep and Circadian Neurobiology research associate Julie A. Williams, PhD. "Many studies have used sleep deprivation as a means to understand how sleep contributes to recovery, if it does at all, but there is surprisingly little experimental evidence that supports the notion that more sleep helps us to recover. We used a fruitfly model to answer these questions." Along with post-doctoral fellow, Tzu-Hsing Kuo, PhD, Williams conducted two related studies to directly examine the effects of sleep on recovery from and survival after an infection.

In the first paper, they took a conventional approach by subjecting fruit flies to sleep deprivation before infecting them with either Serratia marcescens or Pseudomonas aeruginosa bacteria. Both the sleep-deprived flies and a non-sleep-deprived control group displayed increased sleep after infection, what the experimenters call an "acute sleep response."

Unexpectedly, the pre-infection, sleep-deprived flies had a better survival rate. "To our surprise they actually survived longer after the infection than the ones who were not sleep-deprived," notes Williams. The Penn team found that prior sleep deprivation made the flies sleep for a longer period after infection as compared to the undisturbed controls. They slept longer and they lived longer during the infection.

Inducing sleep deprivation after infection rather than before made little difference, as long as the infected flies then got adequate recovery sleep. "We deprived flies of sleep after infection with the idea that if we blocked this sleep, things would get worse in terms of survival," Williams explains. "Instead they got better, but not until after they had experienced more sleep."

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Sleep deprivation increases activity of an NFkB transcription factor, Relish, which is also needed for fighting infection. Flies without the Relish gene do not experience an acute sleep response and very quickly succumb to infection. But, when these mutants are sleep-deprived before infection, they displayed increased sleep and survival rates after infection. The team then evaluated mutant flies that lacked two varieties of NFkB (Relish and Dif). When flies lacked both types of NFkB genes, sleep deprivation had no effect on the acute sleep response, and the effect on survival was abolished. Flies from both sleep-deprived and undisturbed groups succumbed to infection at equal rates within hours.

"Taken together, all of these data support the idea that post-infection sleep helps to improve survival," Williams says.

In the second study, the researchers manipulated sleep through a genetic approach. They used the drug RU486 to induce expression of ion channels to alter neuronal activity in the mushroom body of the fly brain, and thereby regulate sleep patterns. Compared to a control group, flies that were induced to sleep more, and for longer periods of time for up to two days before infection, showed substantially greater survival rates. The fruit flies with more sleep also showed faster and more efficient rates of clearing the bacteria from their bodies. "Again, increased sleep somehow helps to facilitate the immune response by increasing resistance to infection and survival after infection," notes Williams.

Because the genetic factors investigated by the Penn team, such as the NFkB pathway, are preserved in mammals, the relative simplicity of the Drosophila model provides an ideal avenue to explore basic functions like sleep. "Investigators have been working on questions about sleep and immunity for more than 40 years, but by narrowing down the questions in the fly we're now in a good position to identify potentially novel genes and mechanisms that may be involved in this process that are difficult to see in higher animals," explains Williams.

"These studies provide new evidence of the direct and functional effects of sleep on immune response and of the underlying mechanisms at work. The take-home message from these papers is that when you get sick, you should sleep as much as you can -- we now have the data that supports this idea," she concludes.



SOURCE  University of Pennsylvania via EurekAlert

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 Cancer  

Researchers of the University of Konstanz the first to detect cancer cells using the olfactory senses of fruit flies. The technique may help develop an effective, low-cost cancer screening system.

Aresearch unit in an international cooperation project, led by the neurobiologist and zoologist Dr. Giovanni Galizia, has been the first to demonstrate that fruit flies are able to distinguish cancer cells from healthy cells via their olfactory sense.

In an article, published in Scientific Reports, the researchers of the University of Konstanz and the University La Sapienza in Rome, Italy, describe how characteristic patterns in the olfactory receptors of transgenic Drosophilae can be recorded when activated by scent. Not only could a clear distinction be made between healthy cells and cancer cells; moreover, groupings could be identified among the different cancer cells.

Image Source - Galizia et al, Scientific Reports

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"What really is new and spectacular about this result is the combination of objective, specific and quantifiable laboratory results and the extremely high sensitivity of a living being that cannot be matched by electronic noses or gas chromatography", explains Galizia.

Natural olfactory systems are better suited to detecting the very small differences in scent between healthy cells and cancer cells. This fact has already been shown in experiments with dogs; however, these results are not objectifiable and are thus not applicable for a systematic medical diagnosis.

The researchers from Konstanz and Rome used the fact that single odourant molecules dock to the receptor neurons of the flies' antenna and thus activate the neurons. In an imaging technique developed by the researchers, the different odourant molecules of the respective scent samples create different patterns of activated neurons, which fluoresce under the microscope when active, thanks to a genetic modification.

In the experiment five different types of breast cancer cell lines were analysed, compared to healthy cells and clearly divergent patterns were generated. "As not only cancer cells can be distinguished from healthy cells, but also subgroups were discernible within the cancer cells, it seems that even different types of breast cancer cells can be differentiated via the antenna of Drosophila", explains Alja Lüdke, member of the research unit and researcher at the University of Konstanz.

The results of the interdisciplinary research unit, consisting of biologists and engineers from the field of electronic engineering, are a fundamental groundwork for cancer diagnosis: "The high sensitivity of the natural olfactory receptors, paired with the quickness with which we can generate these test results, might lead to the development of a cheap, fast and highly-efficient pre-screening that can detect cancer cells well before we can discover them with the present diagnostic imaging techniques", stresses Galizia.


SOURCE  University of Konstanz, TOP IMAGE WallpapersWide

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 Cancer  

Research by scientists at the University of Exeter has shown that cells demonstrate remarkable flexibility and versatility when it comes to how they divide — a finding with potential links to the underlying causes of many cancers.

New research by scientists at the University of Exeter has shown that cells demonstrate remarkable flexibility and versatility when it comes to how they divide - a finding with potential links to the underlying causes of many cancers.

The study, published in Developmental Cell, describes a number of routes to the formation of a microtubule spindle – the tracks along which DNA moves when a cell divides in order to make two genetically identical cells.

In order to understand the phenomenon, the authors, including Biosciences researchers Dr. James Wakefield, PhD student Daniel Hayward and Experimental Officer in Image Analysis, Dr. Jeremy Metz, combined highly detailed microscopy and image analysis with genetic and protein manipulation of fruit fly embryos.

The innovative research not only describes how the cell can use each pathway in a complementary way, but also that removal of one pathway leads to the cell increasing its use of the others. The researchers also identified that a central molecular complex – Augmin – was needed for all of these routes.

The authors were the first to identify that each of four pathways of spindle formation could occur in fruit fly embryos.

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It was previously thought that, in order for chromosomes – packages containing DNA – to line up and be correctly separated, microtubules have to extend from specific microtubule-organising centres in the cell, called centrosomes. However, this study found that microtubules could additionally develop from the chromosomes themselves, or at arbitrary sites throughout the main body of the cell, if the centrosomes were missing.

All of these routes to spindle formation appeared to be dependent on Augmin - a protein complex responsible for amplifying the number of microtubules in the cell.

Dr. Wakefield said of the project "We have all these different spindle formation pathways working in humans. Because the cell is flexible in which pathway it uses to make the spindle, individuals who are genetically compromised in one pathway may well grow and develop normally. But it will mean they have fewer routes to spindle formation, theoretically predisposing them to errors in cell division as they age."

The group are currently investigating cancer links in light of these findings.


SOURCE  University of Exeter

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 Life Extension  

Can sexual frustration be bad for your health? Male fruit flies that expected sex – and didn’t get it – experienced serious health consequences and aged faster.

Sex may in fact be one of the secrets to good health, youth and a longer life – at least for fruit flies – suggests a new University of Michigan study that appears in the journal Science.

Male fruit flies that perceived sexual pheromones of their female counterparts – without the opportunity to mate – experienced rapid decreases in fat stores, resistance to starvation and more stress. The sexually frustrated flies lived shorter lives.

Mating, on the other hand, partially reversed the negative effects on health and aging.

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"Our findings give us a better understanding about how sensory perception and physiological state are integrated in the brain to affect long-term health and lifespan," says senior author Scott D. Pletcher, Ph.D, professor in the Department of Molecular and Integrative Physiology at the U-M Medical School and research professor at the U-M Geriatrics Center.

"The cutting-edge genetics and neurobiology used in this research suggests to us that for fruit flies at least, it may not be a myth that sexual frustration is a health issue. Expecting sex without any sexual reward was detrimental to their health and cut their lives short."

U-M scientists used sensory manipulations to give the common male fruit fly, Drosophila melanogaster, the perception that they were in a sexually rich environment by exposing them to genetically engineered males that produced female pheromones. They were also able to manipulate the specific neurons responsible for pheromone perception as well as parts of the brain linked to sexual reward (secreting a group of compounds associated with anxiety and sex drive).

"These data may provide the first direct evidence that aging and physiology are influenced by how the brain processes expectations and rewards," Pletcher says. "In this case, sexual rewards specifically promoted healthy aging."

Fruit flies have been a powerful tool for studying aging because they live on average 60 days yet many of the discoveries in flies have proven effective in longer-lived animals, such as mice.

For decades, one of the most powerful ways to slow aging in different species was by limiting their food intake. In a previous study, Pletcher and his colleagues found that the smell of food alone was enough to speed up aging, offering new context for how dietary restriction works.


SOURCE  University of Michigan via Newswise

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 Neuroscience  

Researchers are using the fruit fly to discover how the brain integrates multiple signals to identify one unique smell. It's work that has broader implication for how flies -- and ultimately, people -- learn.

Think of the smell of an orange, a lemon, and a grapefruit. Each has strong acidic notes mixed with sweetness. And yet each fresh, bright scent is distinguishable from its relatives. These fruits smell similar because they share many chemical compounds. How, then does the brain tell them apart? How does the brain remember a complex and often overlapping chemical signature as a particular scent?

Researchers at Cold Spring Harbor Laboratory (CSHL) are using the fruit fly to discover how the brain integrates multiple signals to identify one unique smell. It's work that has broader implication for how flies – and ultimately, people – learn. In work published  in Nature Neuroscience, a team led by Associate Professor Glenn Turner describes how a group of neurons in the fruit fly brain recognize multiple individual chemicals in combination in order to define, or remember, a single scent.

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The olfactory system of a fruit fly begins at the equivalent of our nose, where a series of neurons sense and respond to very specific chemicals. These neurons pass their signal on to a group of cells called projection neurons. Then the signal undergoes a transformation as it is passed to a body of neurons in the fly brain called Kenyon cells.

Kenyon cells have multiple, extremely long protrusions that grasp the projection neurons with a claw-like structure. Each Kenyon cell claw is wrapped tightly around only one projection neuron, meaning that it receives a signal from just one type of input. In addition to their unique structure, Kenyon cells are also remarkable for their selectivity. Because they're selective, they aren't often activated. Yet little is known about what in fact makes them decide to fire a signal.

Turner and colleague Eyal Gruntman, who is lead author on their new paper, used cutting-edge microscopy to explore the chemical response profile for multiple claws on one Kenyon cell. They found that each claw, even on a single Kenyon cell, responded to different chemicals. Additional experiments using light to stimulate individual neurons (a technique called optogenetics) revealed that single Kenyon cells were only activated when several of their claws were simultaneously stimulated, explaining why they so rarely fire. Taken together, this work explains how individual Kenyon cells can integrate multiple signals in the brain to "remember" the particular chemical mixture as a single, distinct odor .

Turner will next try to determine "what controls which claws are connected," which will provide insight into how the brain learns to assign a specific mix of chemicals as defining a particular scent. But beyond simple odor detection, the research has more general implications for learning. For Turner, the question driving his work forward is: what in the brain changes when you learn something?


SOURCE  Cold Springs Harbor Laboratory

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