Publisher Health

The lifespan of a small roundworm that has been used as a key model organism in ageing research is limited by how it self-sacrifices to feed its young, finds a new study led by UCL researchers.
The authors of the new Nature Communications paper say their findings raise questions about how well insights from the Caenorhabditis elegans (C. elegans) worm can be translated to human ageing advances.
C. elegans is widely used as a laboratory animal, and has been central to ageing research for 40 years thanks to discoveries of genes that can be supressed to produce up to a tenfold increase in the worm’s lifespan.
The UCL research team investigated what drives the lifespan of C. elegans, to see if the determining factors are markedly different from the ageing processes of higher (larger, more complex) organisms. In a previous study*, they had already identified an unusual reproductive trait in the worm, called yolk venting, which is a self-destructive process whereby the worm secretes a milk-like fluid through its vulva that is consumed by its offspring to support its grown.
By comparing the worm to other related Caenorhabditis species, the researchers have now found that yolk venting only occurs in Caenorhabditis species that are hermaphroditic (producing both male and female reproductive cells), while such species are also shorter-lived, as reproductive self-destructive processes were linked to shorter lifespan.
The researchers say their findings suggest that C. elegans is one of small number of animals known to have a single act of reproduction which is facilitated by self-destruction (another such species is the Pacific salmon, which swims upstream to spawn and dies soon after). Blocking reproduction, and so blocking self-destruction, is what leads to the huge extension of lifespan in such animals. Because of this, the ageing mechanism in C. elegans is not directly comparable to that of humans.
Corresponding and co-lead author Professor David Gems (UCL Institute of Healthy Ageing, UCL Biosciences) said: “This discovery is groundbreaking because it calls into question 40 years of orthodoxy in the field. The discovery suggests the dream of single gene mutations having a huge impact on human ageing, as in the case of laboratory animals, is more fantasy than reality.”
Yet the researchers say there is still more to learn about human ageing from C. elegans. In an article accompanying the study, published in Frontiers in Cell and Developmental Biology,** the authors present evidence that suicidal reproduction has evolved from more general mechanisms of ageing, that are applicable to humans. This can explain why targeting such mechanisms therapeutically can lead to more modest lifespan extensions in larger animals such as mice.

As the global population grows under a changing climate, the urgency to find sustainable protein sources is greater than ever. Plant-based “meat” and “dairy” products may be popular, but they’re not the only environmentally friendly meat alternatives.
A new study in mice from the University of Illinois Urbana-Champaign suggests replacing traditional protein sources with mealworms in high-fat diets could slow weight gain, improve immune response, reduce inflammation, enhance energy metabolism, and beneficially alter the ratio of good to bad cholesterol.
“In addition to more dietary fiber, nutritionists also recommend eating more high-quality proteins as part of a weight management plan. We knew from an earlier study in roosters that mealworms are a high quality, highly digestible protein source that’s also environmentally sustainable,” said lead study author Kelly Swanson, professor in the Department of Animal Sciences and interim director of the Division of Nutritional Sciences, both in the College of Agricultural, Consumer and Environmental Sciences (ACES) at U. of I.
Swanson’s team fed mice a high-fat diet (46% calories from fat) with casein, a protein from dairy, for 12 weeks before switching to the alternative proteins. Another group, the control, consumed a lean diet with casein throughout the experiment. By the time mealworms were introduced, the high-fat diet group was obese and experiencing metabolic syndrome, a cluster of conditions increasing risk of heart attack, stroke, diabetes, and other health problems.
The mice then started eating two types of mealworms in a dried, powdered form similar to flour, substituting either 50% or 100% of the casein in the diet. During and after 8 weeks on the experimental diets, the research team measured body weight, body composition, blood metabolites, and gene expression of the liver and adipose (fat) tissue.
Mealworm protein didn’t cause obese mice to lose weight, but their rate of weight gain slowed relative to mice consuming high-fat diets with casein. And the benefits went further than that.
“It’s not a weight loss situation; they just slowed their gain with the mealworms,” Swanson said. “The more significant impact was the improvement in their blood lipid profiles. Their LDL, so-called ‘bad cholesterol,’ went down and the HDL, ‘good cholesterol,’ went up. And from a gene expression perspective, inflammation went down and some of the lipid and glucose metabolism genes were altered. Not everything was positive, but metabolically, they were in a better place.”
Some of the benefits might have been associated with chitin, a fibrous material making up the exoskeleton of insects. Swanson said although the role of chitin hasn’t been well studied, it seems to act like a fiber, stimulating beneficial microbial activity in the gut. He has another paper in the works to characterize the effects of mealworms on the mouse microbiome.

An Icahn School of Medicine at Mount Sinai study sheds light on the intricate interplay between mammary adipose (fat) tissue and breast health, and offers exciting possibilities for understanding breast development, lactation, cancer, and obesity and related metabolic disorders.
The study was published today in Nature. The research team was led by Prashant Rajbhandari, PhD, Assistant Professor of Medicine (Endocrinology, Diabetes and Bone Disease), and a member of the Diabetes, Obesity, and Metabolism Institute at Icahn Mount Sinai.
The researchers discovered a new family of locally secreted and locally acting molecules in the breast called “mammokines” that contribute not only to normal mammary biology, but to overall fat cell physiology and energy balance control.
Mammary adipose tissue has long been recognized for its essential role in breast biology. It consists of many different cell types, including fat cells (adipocytes), immune cells, sympathetic nerve fibers, and mammary epithelial cells forming a milk-producing ductal system. Mammary adipocytes play important roles in organizing mammary ducts, and the reverse is true as well.
The new studiesreveal an unexpected role for nerve-activated ductal cells in mammary adipocyte metabolism and heat generation. These mammary duct-secreted mammokines play an important role in controlling mammary gland fat abundance and could potentially orchestrate critical processes involved in breast development, lactation, and overall whole-body metabolic regulation. The findings thus have important implications for breast cancer, lactation-related disorders, newborn health, and metabolic syndromes linked to mammary adipose dysfunction.
“The discovery of mammokines is a significant milestone in our quest to comprehend the complex interplay between mammary adipose tissue and breast biology,” says Dr. Rajbhandari “This breakthrough opens up new avenues for developing targeted interventions to improve breast health and combat related metabolic disorders.”
The research team is currently focused on working to further identify new mammokines and characterize each of them. Their primary aim is to decipher the precise roles of these mammokines and determine whether they regulate systemic glucose and insulin homeostasis through communication with the brain, liver, and pancreas. Additionally, the team is exploring potential therapeutic applications for diseases related to the breast and metabolism.

Imaging techniques such as computed tomography, magnetic resonance imaging, positron emission tomography and ultrasound have become indispensable in the medical world. Each method not only opens up unique insights into the inside of people, but also allows physicians to draw conclusions about defects or functional processes in the human body.
A team of physicists and medical doctors from the Julius-Maximilians-Universität Würzburg (JMU) has now succeeded in making another — and radiation-free — imaging technology ready for use on humans. Its name: Magnetic Particle Imaging (MPI). With the portable scanner they developed, it is possible, among other things, to visualise dynamic processes in the human body, such as the blood flow.
Professor Volker Behr and Dr. Patrick Vogel from the University’s Institute of Physics are responsible for this study; they have now published the results in the journal Nature Scientific Reports.
A sensitive and fast alternative
Magnetic particle imaging is a technique based, as the name suggests, on the direct visualisation of magnetic nanoparticles. Such nanoparticles do not occur naturally in the human body and must be administered as markers. “As with positron emission tomography, which relies on the administration of radioactive substances as markers, this method has the great advantage of being sensitive and fast without ‘seeing’ interfering background signals from tissue or bone,” explains Volker Behr.
MPI is not based on the detection of gamma rays from a radioactive marker like positron emission tomography, but on the response signal of the magnetic nanoparticles to magnetic fields that change over time. “In this process, the magnetisation of nanoparticles is specifically manipulated with the help of external magnetic fields, whereby not only their presence but also their spatial position in the human body can be detected,” says physicist Patrick Vogel, first author of the publication.
A small scanner for big insights
The MPI idea is not new. As early as 2005, the Philips company was able to show the first images of this novel approach in a small demonstrator, which, however, could only take samples a few centimetres in size. And the development of devices suitable for examining humans proved more difficult than expected, leading to large, heavy and expensive constructions.

Viruses, like movie villains, operate in one of two ways: chill or kill.
They can lay low, quietly infiltrating the body’s defenses, or go on the attack, exploding out of hiding and firing in all directions. Viral attacks are almost always suicide missions, ripping apart the cell that the virus has been depending on. The attack can only succeed if enough other healthy cells are around to infect. If the barrage of viral particles hits nothing, the virus cannot sustain itself. It doesn’t die, since viruses aren’t technically alive, but it ceases to function.
So for a virus, the key challenge is deciding when to flip from chill mode into kill mode.
Four years ago, Princeton biologist Bonnie Bassler and her then-graduate student Justin Silpe discovered that one virus has a key advantage: it can eavesdrop on the communication between bacteria. Specifically, it listens for the “We have a quorum!” chemical that bacterial cells release when they have reached a critical number for their own purposes. (The original discovery of this bacterial communication process, called quorum sensing, has led to a string of awards for Bassler and her colleagues.)
Now Bassler, Silpe and their research colleagues have found that dozens of viruses respond to quorum sensing or other chemical signals from bacteria. Their work appears in the current issue of Nature.
“The world is loaded with viruses that can surveil appropriate host information,” said Bassler, Princeton’s Squibb Professor in Molecular Biology and the chair of the department of molecular biology. “We don’t know what all the stimuli are, but we showed in this paper that this is a common mechanism.”
Not only did they demonstrate the strategy’s abundance, but they also discovered tools that control it and send signals that tell the viruses to flip from chill into kill mode.

Scientists have unraveled the step-by-step activation process of a protein with a deep evolutionary history in all domains of life, opening the door to harnessing its functions for use as a biotechnology tool.
The protein belongs to the “superfamily” of Argonaute proteins, which previous research has suggested to be involved in gene silencing, a fundamental process known as RNA interference.
These proteins are well-characterized in eukaryotes — the plants, fungi, animals, humans and other life forms with cells that have a defined nucleus. In prokaryotes that have no nucleus, there are two types of Argonaute proteins, long Argonautes and short Argonautes. The long Argonautes resemble their relatives in eukaryotes both structurally and functionally. In contrast, short Argonautes adopt different structures and perform different functions from other well-studied Argonautes.
This is the first study to detail structures and mechanisms of a short Argonaute, potentially sketching the beginnings of a blueprint for application to future therapeutic purposes.
“The short version of these prokaryotic proteins constitute 58% of all Argonautes, and are now emerging as a hot spot in the field,” said senior author Tianmin Fu, assistant professor of biological chemistry and pharmacology in The Ohio State University College of Medicine. “Among the capabilities we’ve identified is this protein’s precise role in the way bacteria trigger their own death to avoid losing power over their lifecycle through plasmid invasion. Understanding these types of mechanisms is the first step toward efforts to adapt highly effective natural functions for diagnostics and therapies.”
The study is published today (July 26, 2023) in Nature.
In this work, the research team focused on a protein called SPARTA, a short prokaryotic Argonaute (also referred to as Ago), specifically building upon other studies that showed this protein enables Maribacter polysiphoniae bacteria to program their death when they detect a plasmid invasion — when external DNA segments are trying to insert themselves to change bacterial properties.

The results of a novel study presented by Emory researchers during the International AIDS Society (IAS) Conference in Brisbane, Australia, have revealed exciting findings in the pursuit of an HIV cure. The study, led by Monica Reece, a PhD candidate in Emory’s Microbiology and Genetics Program, and directed by Christina Gavegnano, PhD, demonstrates the potential of Jak inhibitors, specifically ruxolitinib, to significantly decay the viral reservoir in people with HIV, offering a novel pathway toward long-term remission or a cure.
The HIV viral reservoir, essentially a small number of immune cells containing dormant virus integrated into the genomes of individuals who have suppressed viral replication with HIV treatment, has posed a major impediment to achieving an HIV cure. These cells are completely undetectable by the immune system because the virus is dormant. But as soon as treatment stops, the virus reactivates.
“The barrier to an HIV cure is that the virus hides inside the DNA of cells,” says Gavegnano, director of the Gavegnano Drug Discovery Program and senior author on the study. “The brass ring is an agent that can eliminate these’reservoir cells,’ which would ultimately eliminate HIV from a person’s body.”
While Gavegnano and her Emory colleagues have shown that Jak inhibitors (Janus kinase inhibitors) could reverse the immune dysfunction caused by HIV since their discovery in 2010, questions about their impact on the HIV reservoir and the exact mechanism contributing to the immunologic improvements have remained unanswered, until now.
The data presented at IAS represented secondary results from a Phase 2a clinical trial centered on investigating ruxolitinib’s effects on viral reservoirs in people with HIV during a five-week regimen, specifically in a subset of individuals with high viral reservoir levels at baseline.
The study measured integrated proviral DNA, which is the genetic material of a virus as incorporated into, and able to replicate with, the genome of a host cell, and examined changes in total, intact only, and defective proviral DNA copies over time. Based on a linear model of decay, the researchers estimated an astonishing 99.99% clearance of the peripheral HIV-1 reservoir in less than three years. These data provide optimism for the use of Jak inhibitors as a backbone for cure-based eradication strategies in the battle against HIV.
Reece, lead author of the study says, “These data suggest that our Jak inhibitors can not only reverse the immune dysfunction that prevents HIV-1 cure, but also significantly decay the reservoir in people living with HIV. Collectively our trial demonstrates a mechanism by which ruxolitinib, or other Jak inhibitors such as baricitinib, also extensively studied by our group, decay the reservoir, which underscores potential for cure-based therapies.”
The profound impact of Ruxolitinib treatment was not limited to reservoir reduction. The study also shed light on several significant biomarkers that were altered by the drug primarily related to: Immune activation: Ruxolitinib exhibited the potential to modulate immune activation, which is crucial in controlling viral replication and maintaining immune health in individuals with HIV. Cell survival: Ruxolitinib demonstrated the ability to impact cell survival, influencing the lifespan of reservoir cells and potentially limiting viral reservoir longevity. Immune dysregulation: The study identified ruxolitinib’s impact on immune dysregulation, offering hope for mitigating the chronic inflammation and immune dysfunction often observed in individuals with HIV.

Recent studies have revealed that mild forms of exercise, such as yoga or walking, can improve mood and enhance executive function, which involves the brain’s prefrontal cortex and refers to the ability to control one’s behavior to achieve a goal. However, the specific neural activity in the human brain that leads to the improvement of executive function during exercise has remained poorly understood due to tecFhnical limitations.
It is often said that the eyes are a part of the brain and can effectively reflect a person’s mental state. In recent years, there has been growing interest in investigating pupil size variations as these are closely linked to the neural activity associated with the brain’s noradrenergic arousal system. Pupillometry, a noninvasive and contactless measurement technique, allows for the assessment of neural activity during aerobic exercise and could serve as an indicator of arousal neural activity. Based on this premise, a research team led by KUWAMIZU Ryuta and SOYA Hideaki hypothesized that changes in pupil size during very light exercise could predict improvement in prefrontal executive function after a single exercise session.
To test this theory, the research team asked a group of healthy young adults to participate in 10-min very light exercise followed by an executive function task. The findings revealed that pupils dilated during the exercise, and the extent of the dilation was an indicator of a subsequent improvement in executive function. Prefrontal cortex activity during the executive function task was examined using functional near-infrared spectroscopy, demonstrating an increase in the activity of the left dorsolateral prefrontal cortex, a region associated with executive function.
These results strongly suggest that the enhancement of prefrontal executive function resulting from very light exercise can be attributed to pupil-linked neural activity, specifically the activation of the brain’s noradrenergic arousal system. Looking ahead, pupil diameter holds promising potential as a novel biomarker that can be used to predict the effects of exercise on the brain.
This work was supported in part by the Japan Society for the Pro- motion of Science (JSPS) 16H06405 (H.S), 18H04081 (H.S.), 21H04858 (H.S.), 20J20893 (R.K.), and 23KJ1169 (R.K.); the Japan Science and Technology Agency (JST) Grant JPMJMI19D5 (H.S.); and the Meiji Ya- suda Life Foundation of Health and Welfare Grant (R.K.). This work was also supported in part by the Inviting Overseas Educational Research Units in University of Tsukuba ( 2016-2023) (to H.S.).

Bandages infused with casein, a protein that occurs naturally in cow’s milk, significantly improved wound healing in rats compared to those in control groups, according to a new study by UCL researchers.
The study, published today in Interface, is the first to test casein’s reputed healing benefits on an animal model. The promising results suggest that casein, which is cheap, abundant and has antimicrobial properties, has potential to replace expensive materials such as silver in wound dressings.
Casein is a protein found in the milk of mammals and is most abundant in cow’s milk, where it makes up to 80% of the substance. In the last decade, interest has grown in casein’s antimicrobial, antioxidant and anti-inflammatory properties, as well as its utility as a high-protein dietary supplement.
In this study, researchers at UCL mixed pure casein with polycaprolactone (PCL), a biodegradable polyester commonly used as a bandage material. They used a technique called pressurised gyration, which was developed at UCL in 2013, to spin this mixture into bandage-like fibres from which they created casein-infused bandages. This would not have been possible with other, more expensive manufacturing methods such as electrospinning.
Rats with identical small skin perforations were split into three groups. The wounds of those in the first group were treated with casein-infused bandages, the second with normal PCL bandages, and the third with no bandages.
Healing progress was checked after three, seven, 10 and 14 days by photographing and measuring the wounds, as well as examining them under a microscope.
The team found that at 14 days the wounds treated with casein-infused bandages healed to 5.2% of their original size, compared to 31.1% in the normal bandage group and 45.6% in the untreated group.

Hospitalized older people who do not follow a Mediterranean diet could benefit from a physical exercise program to prevent hospitalization-associated disability, that is, loss of skills in daily-life activities. Therefore, if the factor of following a Mediterranean diet is included among the variables assessed on the hospital admission of elderly patients, more precise and personalized strategies could be designed to prevent hospitalization-associated disability, which is only frequent in the elderly.
This is one of the conclusions of an article published in the Journal of Nutrition and Healthy Aging and led by experts Mireia Urpi-Sarda, from the Faculty of Pharmacy and Health Sciences, the Institute for Research in Nutrition and Food Safety (INSA-UB) and the Torribera Food Campus of the University of Barcelona, and José Antonio Serra-Rexach, from the Biopathology of Aging Research Group of the Gregorio Marañón Health Research Institute (IISGM), both members of the CIBER on Frailty and Healthy Aging (CIBERFES).
The study notes that hospitalized older adults who eat similarly to a Mediterranean diet also improve their overall condition with exercise and health education guidelines. Notably, in an editorial the journal has highlighted the fact that patients with poorer physical condition show more significant improvements in response to a physical exercise program. Also, it encourages further studies on the influence of dietary patterns on the effects of exercise to prevent hospitalisation-associated disability.
A basic exercise program for older patients
Hospitalization-associated disability is a phenomenon that affects even older patients who have been successfully treated for their condition while in the medical center. In addition, it can also lead to higher economic costs, readmissions, and even a higher mortality in some cases. In this context, physical exercise interventions during hospitalization have been shown to be safe and effective strategies to prevent this functional deterioration in hospitalized older people.
The new study is based on the AGECAR-PLUS project, a randomized clinical study of 260 patients aged 75 years or older at the Gregorio Marañón University Hospital. As part of the study, a group of 109 volunteers — 46% women aged around 87 — were evaluated for adherence to a Mediterranean dietary pattern, urinary polyphenol levels, functional status, and other health parameters at the time of admission and discharge.
José Antonio Serra-Rexach says: “We observed that patients who underwent the physical exercise and health education intervention during hospitalization significantly increased their functional status at discharge, compared to their admission and to patients who did not undergo the intervention. However, to date, there was no evidence of the effect of a healthy diet on functional status in hospitalized older people.”
“A healthy diet pattern, such as the Mediterranean diet, is associated with a lower risk of physical deterioration and weakness in elderly people. Considering that the Mediterranean diet is rich in polyphenols, we have evaluated the monitoring of this dietary pattern through a validated questionnaire, as well as by analyzing the level of polyphenols in urine,” says Professor Mireia Urpi-Sarda, from the UB’s Biomarkers and Nutritional & Food Metabolomics Research Group.
Researcher Alba Tor-Roca, from the Department of Nutrition, Food Sciences and Gastronomy of the UB, notes that “in the study, we observed that in individuals who had a low adherence to the Mediterranean diet when hospitalized, the intervention with physical exercise had a greater and clinically relevant effect on their functional capacities.”
“These results suggest that adherence to the Mediterranean diet may represent an indicator of those older patients with an apparently better response to exercise interventions,” the researchers conclude.