Some of the damaging cell effects linked to ageing could be prevented by manipulating tiny parts of cells, a study shows.
Scientists have shed light on how the harm caused by senescence – a vital cell process that plays a key role in diseases of ageing – could be controlled or even stopped.
Researchers say the findings could have relevance for age-related diseases including cancers and diabetes, although they caution that further research is needed.
During senescence, cells stop dividing. This can be beneficial in assisting wound-healing and preventing excessive growth.
Some aspects of senescence are also harmful and can lead to tissue damage and the deterioration of cell health as seen in diseases of older age.
Scientists at the Medical Research Council’s Human Genetics Unit and the Cancer Research UK Edinburgh Centre at the University of Edinburgh focused on a chain of harmful processes triggered by senescence, known as the senescence-associated secretory phenotype (SASP).
The SASP is a cascade of chemical signals that can promote damage to cells through inflammation.
The researchers showed that manipulating a cell’s nuclear pores– gateways through which molecules enter the heart of the cell – prevented triggering of the SASP.
Findings also show that DNA had to be reorganised in space within in the cell’s nucleus in order for the SASP to be triggered.
Researchers say the study sheds light on the fundamental workings of the cell and could be instrumental in understanding cell ageing.
The study is published in Genes and Development.
Professor Wendy Bickmore, Director of the Human Genetics Unit at the University of Edinburgh’s Medical Research Council Institute of Genetics and Molecular Medicine, who led the study, said: “These findings provide us with a much clearer understanding of how senescence causes cell damage. Whilst we are some way from being able to halt the damage caused by the ageing process, we hope that this advance will open up avenues to explore how we might slow some of the harm that stems from senescence. This could be of relevance to the many conditions that tend to affect us as we grow older.”
(HealthDay)—A global study about what men and women want in a mate seems to confirm—to a point—long-established stereotypes.
Men still go for looks—in general they said their preference is for a partner who is younger and physically attractive. Women said they’d prefer an older partner who’s ambitious and has good financial prospects.
The researchers, from the University of Texas at Austin, explained that these responses, which came from 10,000 participants in 33 countries, can probably be traced back to the respective mating challenges men and women faced throughout the course of human evolution.
On a more positive note, both sexes do gravitate toward some of the same less superficial traits—a pleasant disposition, good social skills, and similar politics and religious beliefs.
Another study with an international team of researchers found that men and women approach relationships in another similar way: They’re both influenced by deal breakers, or perceived negative traits, and deal makers, the traits that they find most appealing.
Both sexes process these pros and cons simultaneously when they meet someone new and apply higher standards when considering someone for a long-term relationship. Also, deal breakers have a greater influence on choices than deal makers—it’s easier to be turned off by the negatives than to be turned on by the positives.
Deal breakers range from unhealthy—even dangerous—lifestyle habits like substance abuse to being too needy, lazy or unkempt. Deal makers include, not surprisingly, being attractive and having a solid career, but also being kind, smart and having a good sense of humor.
With our appetite for low or zero sugar products increasing, artificial sweeteners are big business.
Food or drinks containing artificial sweeteners are often marketed as a healthier option, and it’s understandable why. Because artificial sweeteners are significantly sweeter than sugar, they can be used in very small amounts and contribute little to no calories. There are lots of types, but the most well researched are aspartame and saccharin.
A possible link between artificial sweeteners and cancer has been reported in the media. But despite lots of research in this area, there’s no convincing evidence that sweeteners in our food and drink increase the risk of cancer.
While there’s nothing to worry about from a cancer perspective, questions still remain about whether or not artificial sweeteners can help us lose weight. And as being overweight or obese increases the risk of 13 types of cancer, knowing whether they help is important.
But getting a solid answer to this question is tricky. Diet is notoriously difficult to study and so far, researchers have reached different conclusions. Overall, it looks like artificial sweeteners like aspartame aren’t causing harm, but they’re not having the big weight loss benefits that some people expected either.
Can we have our cake and eat it too?
If sweeteners are replacing a high calorie alternative, it seems logical that by reducing calories they should help with weight loss.
But whether this is the case is tricky to prove. It’s difficult to study the long-term impact of a specific part of our diet for lots of reasons. For one, measuring exactly how much people consume is hard. And there are lots of other things that could explain any differences – like other elements of a person’s diet or how much they exercise – so we need large studies that take these things in to account.
Most studies have looked at artificially sweetened drinks rather than sweeteners in foods, and the results are mixed. For this reason, the European Food Safety Authority won’t allow products containing artificial sweeteners to carry a weight loss health claim.
A 2016 review found that people using artificial sweeteners had both a lower calorie intake and reduced body weight. But these results should be treated with a healthy dose of scepticism as the study was conducted and funded by the International Life Sciences Institute, whose members include companies such as Coca-Cola, Red Bull and Pepsi. Each of these companies has a vested interested in the artificial sweetener business.
The results also don’t fully tally up with a more recent, independent analysis of 56 studies. This analysis found very little evidence to suggest low energy artificial or natural sweeteners, like stevia, are helping lots of people to lose weight.
But when 3 studies were picked out that only included overweight or obese adults, artificial sweeteners did provide a small benefit to weight loss. While positive for this group of people, the researchers say that larger and longer-term studies are needed to confirm this.
If not weight loss, then what about weight gain?
Surprisingly, some research has found that sweeteners might make us gain weight. But the latest review didn’t agree with this.
This raises an important question: if products containing artificial sweeteners contain less calories, why doesn’t the evidence show they are helping us to lose weight?
One explanation is something called ‘reverse causality’ – whereby people who are already overweight or obese are more likely to be choosing food or drinks with sweeteners to help with weight loss. This makes it difficult to say whether the artificial sweeteners or weight gain came first, or how one may affect the other.
But some researchers think there might be more going on, including effects on our gut health, appetite and desire for sweet foods.
But these are unproven theories.
Are sweeteners actually making us hungrier?
Throughout the day, our gut sends messages to our brain in the form of hormones. These hormones tell our brain when we are hungry or full. There has been some suggestion that sweeteners could interfere with these messages, and therefore make us eat more rather than less.
”When we eat food containing sugar, the gut produces more of the hormone that tells our brain we are full, and less of the hormone that tells our brain we are hungry. Currently, the evidence suggests that sweeteners don’t prompt the release of either of these gut hormones in humans,’ says Dr. Ana Pinto, a nutrition researcher from King’s College London (KCL).
Does a diet or low-calorie option at lunch equal more at dinner?
If sweeteners aren’t affecting our gut, is there a psychological effect?
Some research has proposed a reward effect, in which we feel we have some ‘calories to spare’ if we have replaced a high calorie product with a diet alternative.
Daphne Katsikioti, who also studies nutrition at KCL, explains: “‘Some researchers have suggested that when we eat or drink products containing artificial sweeteners, we later compensate for the ‘missing’ energy by eating more.”
But she adds that there’s good evidence to suggest that this doesn’t happen and that artificial sweeteners can be helpful to reduce calories.
Finally, some people have suggested that the intense sweetness that comes from sweeteners could lead to a particularly sweet tooth in the long term. The latest review found very little evidence of this, so more research is needed to pin down if this a possible side effect of artificial sweeteners.
To sweeten or not to sweeten?
Despite the theories, the European Food Safety Authority have ruled that artificial sweeteners in food and drink pose no threat to our health if consumed within daily allowances. For aspartame, this is equivalent to 15 cans of diet coke. That’s a stark contrast to what we know about the harms of having too much sugar.
But products containing sweeteners often don’t offer much nutritional benefit. And the lack of convincing evidence that they can help with weight loss shouldn’t be overlooked.
The take-home message is sugary drinks aren’t a silver bullet for weight loss. But if you drink a lot of sugary drinks and think a diet version might help you cut down on sugar, that’s a good step and is very unlikely to do you any harm.
The UCLA scientists observed consistent bursts of electrical activity in the developing brain of fruit flies. T4 and T5 indicate individual neurons firing.
Neurons somehow know which of their neighbors to connect with and which to avoid in the crowded environment of the central nervous system. But how?
Using fruit flies, neuroscientists from the David Geffen School of Medicine at UCLA observed that neurons displayed periodic bursts of electrical activity early in brain development, when the larva is still developing. The coordinated activity appears to be internally driven—not triggered by something outside of the brain. The findings suggest that the signals could help neurons find each other to form networks and wire the developing brain.
The scientists imaged the electrical activity of 15 types of neurons in the brain region involved in processing vision. All of the cells fired signals at each other for two days until the adult fly emerged. Of note, the consistent firing bursts reflect patterns of connectivity that have already been recognized in the adult fly’s brain.
The authors suspect that the signaling ensures that connections established in the absence of cellular communication work properly in larger networks of neurons that collaborate to carry out specific functions.
Although this type of developmental spontaneous activity has been known for 30 years to occur in humans and other vertebrates, the UCLA study is the first time that scientists have observed it in an insect whose brain was believed to develop in the absence of such activity. The discovery of a similar phenomenon in the fruit fly suggests that neurons’ activity during development may be an essential phase of building a complex brain.
The scientists’ next step will be to explore where the activity originates, how it’s organized across the brain and how it contributes to brain development.
The findings were published online by Neuron and will appear later in the journal’s print edition.
Left: Image of a soft hydrogel with normally developing cell cultures (filled triangles). Right: Image of a stiffened, tumor-like hydrogel with transformed cells (open triangles). Credit: Matt Ondeck and Jesse Placone
A study provides new insight into how the stiffening of breast tissue plays a role in breast cancer development. By examining how mammary cells respond in a stiffness-changing hydrogel, bioengineers at the University of California San Diego discovered that several pathways work together to promote the transformation of breast cells into cancer cells. The work could inspire new approaches to treating patients and inhibiting tumor growth.
The team reported their findings in a paper published online on Feb. 12 in the Proceedings of the National Academy of Sciences (PNAS).
“By dynamically modulating the stiffness of the microenvironment, we can better mimic what happens during the transformation of breast cells to a malignant state in a dish,” said senior author Adam Engler, a professor of bioengineering at the UC San Diego Jacobs School of Engineering.
The study is part of a growing body of research showing that mechanical forces—not just genetic and biochemical signals—play a key role in the development and spread of cancer. In the past, researchers have found that modeling stiff tissue environments in vitro promoted tumor growth.
But these models often do not fully recreate what’s happening in the body because they are static, Engler noted. “Tissue stiffening is a dynamic process. Mammary tissue doesn’t just start out stiff, this is something that develops over time,” said Engler.
So Engler’s approach was to use a material system in which the stiffness could be tuned dynamically while cells are inside, and then see how the cells respond to that change in stiffness.
“We’re trying to mimic the process of fibrosis during the progression of tumor development,” said Jesse Placone, a postdoctoral fellow in Engler’s lab and a co-first author of the study. “As a tumor site forms, the local stiffness of the tissue increases. And by modeling this dynamic stiffness, our system is significantly more representative of what happens in vivo.”
The team used a hydrogel called methacrylated hyaluronic acid, a soft material that can be stiffened to varying degrees with exposure to free radicals and UV light. They first stiffened the hydrogel enough to mimic the stiffness of normal breast tissue. Then, they cultured mammary epithelial cells in the gel. After the cells matured, the gel’s stiffness was increased to that of a breast tumor. The amount of UV exposure required in this step was not enough to harm the cells, the team noted.
They discovered that stiffening triggers multiple pathways that together signal mammary cells to become cancerous. Key players of these pathways include the proteins TWIST1, TGF-beta, SMAD and YAP.
“In a dynamic environment, we found that these different pathways act cooperatively. It’s not enough to inhibit just one of those pathways as was previously shown in studies modeling static, stiff environments,” said Engler. “From a clinical perspective, this suggests that a single drug approach may not work for all patients with breast cancer tumors.”
The team also discovered that a subpopulation of mammary cells do not respond to stiffening. Engler says this is good news for women as fewer cells than previously thought may turn into cancer as a result of the environment alone. Such a result, if it translates to patients, could mean fewer or smaller primary tumors.
The team next plans to explore drug candidates to inhibit the pathways and study their effects on tumor progression. This research was done primarily on genetically controlled cell lines, so the team will follow up with studies on patient-derived cell lines.
Researchers of the University of Barcelona (UB) have used massive sequencing techniques with samples from patients to determine the evolution of the hepatitis A virus. The results, published in the journal EBioMedicine, show the presence of variants of the virus that could escape the effects of the vaccine. The study, led by the Research Group on Enteric Viruses of the UB, in collaboration with Vall d”Hebron Research Institute (VHIR) and the Public Health Agency of Barcelona (ASPB), has implications for vaccination policies.
Hepatitis A virus antigenic variants
Hepatitis A is a liver inflammation caused by a virus. Its symptomatology is minimal and can disappear after the first few weeks, but in some cases, the disease can last for months. Among the most affected groups are men who have sex with other men (MSM).
This study analysed samples from MSM patients, both vaccinated and non-vaccinated, who contracted the virus during an outbreak of hepatitis A in Barcelona (2016-2018). The objective was to study the evolution of the virus and check whether there are emerging variants that can escape the effects of the vaccine. “We identified antigenic variants in vaccinated and non-vaccinated patients, but only the former increase in number, which suggests the positive selection,” says Rosa Maria Pintó.
The appearance of hepatitis A virus antigenic variants could become a threat to public health and the use of available vaccines. “If we select a variant that escapes the vaccine, it could stop being effective. The study shows that, in cases such as the one that occurred due the lack of vaccines, this can happen,” says the researcher.
Reviewing vaccination practice
In some countries, controlling recent outbreaks of hepatitis A has been inhibited by the low coverage of vaccination and lack of vaccines, which made health administrations apply restrictions in the doses.
During the outbreak, these restrictions particularly affected people in the MSM group. “If a few doses of vaccination are given, or if the common doses were given long ago, or the vaccine is given to patients who caught the virus weeks ago, those variants of the virus that avoid the effects of the vaccine can be selected. This is especially relevant in the MSM group, since the virus dose through risky sexual practises is very high, and circulating antibodies are not enough to neutralize the inoculum or the first produced viruses,” says Rosa Maria Pintó.
Researchers therefore recommend giving two doses of the vaccine, and in some situations, suggest giving additional booster doses. Apart from specifying the vaccination protocol, the expert states they should “work in order to have easier-to-get vaccines so there are no vaccine shortages and doses do not have to be reduced.”
New research reveals RNAs, which are crucial for cells to produce proteins, are also involved in protein aggregation, where proteins do not fold properly and ‘clump’ together into aggregates. If cells cannot clear these away, they become toxic and prevent cells working properly. This discovery, led by scientists at the Centre for Genomic Regulation (CRG) in Barcelona, reveals that RNAs act as a ‘scaffold’ to hold several proteins that stick to RNAs together, and that certain RNA molecules with distinct properties attract more proteins and encourage proteins to aggregate. They also investigated how an RNA called FMR1 is implicated in a neurodegenerative disease called Fragile X Tremor Syndrome, or FXTAS.
Many neurodegenerative diseases are linked to protein aggregation, including amyotrophic lateral sclerosis and Alzheimer’s disease. We know that proteins can form toxic aggregates, but until now, the contribution of nucleic acid molecules such as RNA has been up for debate.
CRG researcher and ICREA Research Professor Gian Gaetano Tartaglia and CRG Alumni Teresa Botta-Orfila, and currently at Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), wanted to understand how RNA can promote aggregation. In their research, published in the journal Cell Reports, they discovered that specific RNAs do indeed interact with many proteins within cells, and that these RNAs have distinct properties – they are structured, have a long area of untranslated genetic code called a UTR region, and often contain several repeats of genetic code (called CGG expansions) within them.
“Using theoretical tools, Fernando Cid in the group investigated how an RNA called FMR1 attracts proteins in FXTAS,” explains Gian Gaetano Tartaglia. “Together with Teresa we then worked out the proteins that bind to FMR1 using novel lab approaches and identified one of them as a protein called TRA2A. Using cells, mouse models of FXTAS and post-mortem samples from patients, we confirmed that TRA2A aggregates with FMR1 in this disease and we studied the consequences of its aggregation. Now that we know the components of some of these aggregates, we can begin to understand what is causing this disease and it may reveal new ways to treat it.”
Botta-Orfila continues: “We were surprised to find that our predicted interactions could act as biomarkers for the disease. And it was particularly exciting that we detected the TRA2A protein in the brains of people with the disease – it was one of the most important findings in my time at CRG. Lots of things suddenly made sense. The TRA2A protein that we discovered was involved in FXTAS is involved in RNA splicing, a crucial process that ensures the pieces of genetic code are in the correct order and produce the right protein. Because this protein aggregates in FXTAS, it isn’t carrying out the splicing process correctly – and as a result many RNAs are altered and cannot work properly.”
And the team’s biomarker discovery has raised more interesting questions that they’d like to answer. “Many of the genes that we found were deregulated because of protein aggregation are related to brain development, which is a key factor in disease development,” explains Gian Gaetano Tartaglia.
The team now have an arsenal of proteins to test for FXTAS, and they would like to extend their work to other complex diseases. In the longer term, they would also like to discover the function of sticky RNAs. Together, this work could improve our understanding of complex diseases where proteinaggregation is important and could ultimately reveal new ways to treat them.
