Publisher Health

On November 15, 2022, the 8 billionth person on the planet was born. With concerns about food security on the rise, experts are asking: how will we feed everyone? Climate change, natural resource depletion, soil erosion, and fossil fuel use in farming make the task even more challenging. We need to do something differently, but what?
Barath Raghavan, an associate professor of computer science at USC Viterbi, is rethinking traditional farming practices by developing computational tools to help farmers design, develop, and manage sustainable farming methods. Raghavan, a member of the California Rare Fruit Growers organization, currently grows more than 150 different edible plants in his yard. A decade ago, he started to combine his interests by researching how computing could make agriculture more sustainable.
Raghavan calls this new area of research “computational agroecology,” uniting technology and farming expertise to develop diverse agricultural landscapes based on natural ecosystems. From crop selection to planting to irrigation, the method allows farmers to explore thousands of different potential designs to optimize food production without fossil fuel-derived pesticides.
“How can we design an ecosystem that is as productive and sustainable as a natural forest, but instead of producing food for wildlife, it’s producing food for people?” said Raghavan.
“It’s an incredibly hard problem because designing an ecosystem is a super complex, dynamic, natural system. We’re trying to build computing tools that can figure out how ecosystems work, so we can grow food plentifully and sustainably.”
“A totally new way to think about agriculture”
In a new paper published in PNAS Nexus on March 16, Raghavan and his colleagues propose “a totally new way to think about agriculture and the benefits it can have for research and farming,” said Raghavan.

In this study, the researchers reconceptualize agriculture as a search through a “state space,” which represents all possible configurations of a system — in this context, agricultural land.
To better understand the concept of a state space, imagine a box of blocks: each block could be red, blue or yellow. The state space would consist of all the possible ways to arrange these blocks, such as all red, blue or green, or a combination of the three colors.
In the same way, a state space for an agricultural system might consist of all the possible variables that the system can take — such as crop or soil type, weather conditions, irrigation, fertilization or pest control.
This allows agricultural researchers and farmers to explore the different paths and strategies available — taking different “blocks” or variables and placing them together to see what works.
“Once we can conceive of a farm this way, we can then reframe many … farming planning questions.” Barath Raghavan.

Essentially, an agricultural “sandbox” to determine optimal configurations to increase crop yield, improve sustainability, and discover entirely new combinations of crops that grow well together.
For instance, the framework enables analytics and machine learning that could allow researchers to analyze the patterns between crop yield and soil moisture content or simulate growing different types of crops together for biodiversity.
“Once we can conceive of a farm this way, we can then reframe many research questions and farming planning questions as a search through the space of all possible states the farm could possibly end up in, with certain states being more desirable than others,” said Raghavan.
“This allows us to compare and contrast different approaches to farming, explore and combine techniques, and then search the state space in simulation for new farming techniques that have never been tried before and where trial and error in the real world would be far too expensive and time-consuming.”
“Playing a chess game with nature”
For example, in Southern California, farmers have recently discovered that high-quality coffee can grow plentifully between avocado trees. But figuring out the right way to do that, and maybe even add another couple of crops that work well together, is site specific.
“Each farmer doesn’t have the time or ability to do trial and error for years to figure out the right way to grow a half dozen crops on their land,” said Raghavan.
“Instead, with the conceptual framework and eventually software framework of state spaces, a farmer could spell out an objective — such as diversified harvest with high yield and possible high profit for a specific piece of land — and have the system explore the state space and produce possible plant mixtures, placement, and management techniques that meet the farmer’s criteria.”
Raghavan compares the process to “playing a chess game with nature, but one that is both competitive and collaborative.”
“You’re making moves on the chessboard, which is your land, and nature is making moves too. Pests are going to eat one crop; a flood is going to damage another. What we are building is a computational framework that allows you to explore all the different ways that you might ‘play’ this game of chess with nature so that we can come up with the best one for your land.”
The group including Raghavan recently received a grant from the U.S. Department of Agriculture’s National Institute of Food and Agriculture for their research in this area. Now, the team is working through possible use cases with researchers and farmers to incorporate specific use cases and to develop software that can make it easy to simulate and explore state spaces.

Published14 hours agoShareclose panelShare pageCopy linkAbout sharingA 23-year-old has called for a ban on using sunbeds, after he was diagnosed with a type of skin cancer at the age of 21.Jak Howell, from Swansea, was just 16 when he started using sunbeds four to five times a week for up to 18 minutes at a time.A bleeding mole that appeared on his body resulted in a life-changing cancer diagnosis.He described his sunbed usage from such an early age as his “biggest regret”.The current law in Wales is that under-18s are not allowed to use sunbeds, with salons required to ask for identification and follow strict safety protocols, according to an industry body. Whilst receiving treatment, Mr Howell turned to TikTok to share his experience and campaign for others to be cautious.Despite being cancer-free since December, he described a want “to fit in” as his reason for starting sunbeds so young.Tanning salons let in girls with no ID checksScientists say a ban on sunbeds could save lives’I lost an ear to my tanning addiction'”A massive part of it was that I was hanging around with people that were a lot older than me,” he told BBC Radio Wales Breakfast.”So I just followed the crowd, went with it and it was my biggest regret. “Being so young, I thought I was invincible. I’ll be completely honest I didn’t want to listen, which completely backfired on me.”Mr Howell said when he went into sunbed shops at 16, there was no signage or warnings to highlight the dangers of their use. “It was just ‘go on the sunbed and leave’, that was it,” he said.”The first sunbed I ever went in, there wasn’t even a receptionist. You just put your money in the machine, and you just went straight in. “If I could go back now and speak to somebody about it, I’d definitely listen more.”Image source, Getty ImagesAs “quite an active person”, he started to notice himself feeling “tired and really down all the time”.”I just noticed something wasn’t right in my body – and that is coming up to two years ago at the end of this month, ” he said.”There was a small mole on my back, so I had to send a picture to my GP, and the GP referred me straight to the hospital where they took a biopsy and then ten days later I had the call.”There’s nothing like it. The only way I can describe it was just like a grenade going off in my soul. It was the most empty feeling I’ve ever had in my life.”I want to go all the way with it, I want to get these sunbeds banned.”Image source, Getty ImagesChairman of The Sunbed Association, Gary Lipman, said: “Sunbed use by under-18s has been against the law across the UK since 2010 and our members who represent professional salon operators have strict protocols in place to ensure the law is complied with. “Sunbed Association members also have trained staff to screen customers for any contra-indications to tanning as well as record the number of sessions taken to ensure compliance with the long-standing regulation of no more than 60 sessions per year.”A ban on underage sunbed use has been in place in Wales since 2011.Tanning shop owners who flout this law face fines or having their licences taken away.It was introduced after Cancer Research UK said using a sunbed before the age of 35 significantly increases your chance of getting skin cancer.The Welsh government said: “In 2011, the Welsh government introduced legislation which introduced further, tighter controls and balanced measures to protect and inform those over 18 who choose to use sunbeds.”Since then, the law requires premises to display information on sunbeds about the risk of skin cancer and eye damage.”More on this storyTanning salons let in girls with no ID checks4 July 2022Scientists say a ban on sunbeds could save lives20 May 2022’I lost an ear to my tanning addiction’17 February 2020

Brains are like puzzles, requiring many nested and codependent pieces to function well. The brain is divided into areas, each containing many millions of neurons connected across thousands of synapses. These synapses, which enable communication between neurons, depend on even smaller structures: message-sending boutons (swollen bulbs at the branch-like tips of neurons), message-receiving dendrites (complementary branch-like structures for receiving bouton messages), and power-generating mitochondria. To create a cohesive brain, all these pieces must be accounted for.
However, in the aging brain, these pieces can get lost or altered and no longer fit in the greater brain puzzle.
“Fifty percent of people experience loss of working memory with old age, meaning their ability to hold and manipulate information in the short-term decreases,” says co-first author Courtney Glavis-Bloom, a senior staff scientist in Salk Institute Professor John Reynolds’ lab. “We set out to understand why some individuals maintain healthy working memory as they age, while others do not. In the process, we discovered a novel mechanism for the synaptic basis of cognitive impairment.”
Prior studies had found that brains lose synapses as they age, and the researchers saw this pattern in their animal model, too. But when they looked at the synapses that remained, they found evidence of a breakdown in coordination between the size of boutons and the mitochondria they contained. A fundamental neuroscientific principle, the ultrastructural size principle, explains that whenever one part of the synaptic complex changes in size, so too must all the other parts. The synapse, the mitochondria, the boutons — all these parts must scale in accordance with one another. Before the Salk team’s study, published in Frontiers in Aging Neuroscience on April 12, 2023, nobody had asked whether this principle could be violated with age or disease.
“To examine this, we turned to electron microscopy,” says co-first author Casey Vanderlip, a former research assistant in Reynolds’ lab. “This enabled us to visualize these components across many synapses. We found that synaptic loss occurred with healthy and impaired aging, but what differed was the breakdown in the correlation between the sizes of boutons and their mitochondria.”
“It is a ripple effect, with unfathomably small synaptic structures altering networks of neurons, brain function, and behavior,” says Glavis-Bloom. “Investigating these microscopic dysfunctions is uncharted territory that could revolutionize our understanding of aging and its impact on cognition.”
The team found that adherence to the ultrastructural size principle was essential for avoiding working memory impairment with age. By viewing violation of the ultrastructural size principle and mitochondria-related failures as the key to age-related cognitive impairment, the study ushers in a new era for aging research.
“The images we have captured of synapses are snapshots of a dynamic process,” says Reynolds, holder of the Fiona and Sanjay Jha Chair in Neuroscience. “With these snapshots in hand, we can begin to think first about the mechanisms that coordinate the expansion and contraction of the various parts of the synaptic complex, then ask how disruption of these mechanisms can explain age-related cognitive decline. This opens an entirely new way of thinking about cognitive decline that could lead to new targets for future therapeutics.”
Other authors include Sammy Weiser Novak and Uri Manor of the Salk Institute; and Masaaki Kuwajima, Lyndsey Kirk, and Kristen M. Harris of the University of Texas at Austin.
The work was supported by an Allen Initiative in Brain Health and Cognitive Impairment award made jointly through the American Heart Association and the Paul G. Allen Frontiers Group (19PABH134610000AHA), the National Institutes of Health (1R21AG068967-01, P30014195), the National Science Foundation (2014862), the Kavli Institute for Brain and Mind at UC San Diego (Innovative Research Grant 2021), the Waitt Foundation, the Larry L. Hillblom Foundation, the Don and Lorraine Freeberg Foundation, and the Conrad Prebys Foundation.

In adolescents, sedentary time may increase heart size three times more than moderate-to-vigorous physical activity, a paper published in the Scandinavian Journal of Medicine & Science in Sports concludes. The study was conducted in collaboration between the University of Bristol in the UK, the University of Exeter in the UK, and the University of Eastern Finland. The researchers explored the associations of sedentary time, light physical activity, and moderate-to-vigorous physical activity with cardiac structure and function.
Recent World Health Organization reports and guidelines note that more than 80% of adolescents across the globe have insufficient physical activity per day. Physical inactivity has been associated with several non-communicable diseases in adults such as cardiovascular diseases, type 2 diabetes, and cancer. In the pediatric population, the majority of movement behaviour studies have focused on the effect of sedentary behaviour and physical activity on cardiometabolic health which includes blood pressure, insulin resistance, blood lipids, and body mass index.
There has been a gap in knowledge on the effect of sedentary time and moderate-to-vigorous physical activity on cardiac structure and function in large adolescent populations due to the scarcity of device-measured movement behaviour and echocardiography assessment in the pediatric population. A higher left ventricular mass, which indicates an enlarged or hypertrophied heart, and a reduced left ventricular function, which indicates decreased heart function, may in combination or independently lead to an increased risk of heart failure, myocardial infarction, stroke, and premature cardiovascular death.
The current study, which used data from the University of Bristol study Children of the 90s (also known as the Avon Longitudinal Study of Parents and Children) included 530 adolescents aged 17 years who had complete measurements of fat mass, muscle mass, glucose, lipids, an inflammation marker, insulin, smoking status, socio-economic status, family history of cardiovascular disease, echocardiographic cardiac function and structure measures, and accelerometer-based measure of sedentary time, light physical activity, and moderate-to-vigorous physical activity.
On average, adolescents spent almost 8 hours/day sedentary and about 49 minutes/day in moderate-to-vigorous physical activity in this new study. It was observed that both sedentary time and moderate-to-vigorous physical activity were associated with higher left ventricular mass. However, the increase in cardiac mass (3.8 g/m2.7) associated with sedentary time was three times higher than the cardiac mass increase (1.2 g/m2.7) associated with moderate-to-vigorous physical activity. This finding was observed in adolescents irrespective of their obesity status, i.e among adolescents who had normal weight and those who were overweight or obese. Importantly, light physical activity was not associated with an increase in cardiac mass but was associated with better cardiac function estimated from left ventricular diastolic function.
“This novel evidence extends our knowledge of the adverse effects of sedentary time on cardiac health. It is known among adults that a 5 g/m2 increase in cardiac mass may increase the risk of cardiovascular disease and death by 7 — 20%. Engaging in moderate-to-vigorous physical activity also slightly enlarged the heart but it seems an acceptable negative side effect considering several other health benefits of moderate-to-vigorous exercise. Hence, public health experts, health policymakers, high school administrators and teachers, pediatricians, and caregivers are encouraged to facilitate adolescent participation in physical activity to enable a healthy heart,” says Andrew Agbaje, a physician and clinical epidemiologist at the University of Eastern Finland.
Dr Agbaje’s research group (urFIT-child) is supported by research grants from Jenny and Antti Wihuri Foundation, the Finnish Cultural Foundation Central Fund, the Finnish Cultural Foundation North Savo Regional Fund, the Orion Research Foundation sr, the Aarne Koskelo Foundation, the Antti and Tyyne Soininen Foundation, the Paulo Foundation, the Yrjö Jahnsson Foundation, the Paavo Nurmi Foundation, the Finnish Foundation for Cardiovascular Research and the Foundation for Pediatric Research.

Early diagnosis and treatment of Alzheimer’s disease requires reliable and cost-effective screening methods. Researchers at Karolinska Institutet in Sweden have now discovered that a type of sugar molecule in blood is associated with the level of tau, a protein that plays a critical role in the development of severe dementia. The study, which is published in Alzheimer’s & Dementia, can pave the way for a simple screening procedure able to predict onset ten years in advance.
“The role of glycans, structures made up of sugar molecules, is a relatively unexplored field in dementia research,” says the study’s first author Robin Zhou, medical student and affiliated researcher at the Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet. “We demonstrate in our study that blood levels of glycans are altered early during the development of the disease. This could mean that we’ll be able to predict the risk of Alzheimer’s disease with only a blood test and a memory test.”
In Alzheimer’s disease, the neurons of the brain die, which is thought to be a result of the abnormal accumulation of the proteins amyloid beta and tau. Clinical trials for Alzheimer’s drugs show that treatment should commence early in the pathological process, before too many neurons have died, to reverse the process before it is too late.
More blood biomarkers needed
There is both a practical and a financial need for non-invasive screening methods for Alzheimer’s. Markers in blood are preferable, as taking samples of the cerebrospinal fluid is more difficult and brain imaging is expensive.
Researchers at Karolinska Institutet have now shown that the level of a certain glycan structure in blood, denoted bisected N-acetylglucosamine, can be used to predict the risk of developing Alzheimer’s disease.

The research group has previously demonstrated a link between tau protein and glycan levels in people with Alzheimer’s disease, but these analyses were done on cerebrospinal fluid. Glycans are sugar molecules found on the surface of proteins, the building blocks of life, and determine the location and function of these proteins in the body.
By measuring blood glycan levels the researchers found that individuals with matching levels of glycans and tau were over twice as likely to develop Alzheimer’s-type dementia.
“We also show that a simple statistical model that take into account blood glycan and tau levels, the risk gene APOE4 and a memory test, can be used to predict Alzheimer’s disease to a reliability of 80 per cent almost a decade before symptoms such as memory loss appear,” says corresponding author Sophia Schedin Weiss, docent at NVS, Karolinska Institutet.
17-year follow-up
The results are based on 233 participants of the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K). The samples were collected between 2001 and 2004, and the participants were monitored regularly with respect to factors such as memory loss and the presence of dementia. The follow-ups were carried out every three to six years and continued for 17 years.
The researchers will now be analysing blood samples from the remaining participants of the SNAC-K study as well as from participants of other aging studies in and outside Sweden.
“We’re collaborating with researchers in primary care in Sweden to evaluate different biomarkers for dementia at primary health care centres,” says Dr Schedin Weiss. “We hope that glycans in the blood will prove to be a valuable complement to current methods of screening people for Alzheimer’s disease that will enable the disease to be detected early.”
The study was conducted by researchers in Lars Tjernberg’s research group at the Division of Neurogeriatrics at Karolinska Institutet in collaboration with the Aging Research Centre at Karolinska Institutet, the Stockholm Gerontology Research Center and Karolinska University Hospital.

Developing and testing new treatments or vaccines for humans almost always requires animal trials, but these experiments can sometimes take years to complete and can raise ethical concerns about the animals’ treatment. Now, researchers reporting in ACS Central Science have developed a new testing platform that encapsulates B cells — some of the most important components of the immune system — into miniature “organoids” to make vaccine screening quicker and greatly reduce the number of animals needed.
Vaccines introduce the immune system to an antigen, which can be either part or all of a virus or bacterium, allowing the body to prepare itself for a future exposure by programming its B cells to make antibodies against the antigen. Certain bacteria coat themselves in a polysaccharide “disguise,” however, requiring specialized conjugate vaccines, such as those that protect against pneumonia and meningitis. In this type of approach, a piece of the antigenic polysaccharide is attached, or conjugated, to a carrier protein the body can recognize. But exactly how conjugate vaccines interact with B cells to induce an immune response isn’t fully understood.
The traditional way of testing vaccines involves injecting them into animals and waiting weeks or months for the result. And when developing a whole new class of vaccine or focusing on a new target, scientists often need to evaluate many vaccine candidates, requiring numerous animal studies. To speed up the process and address ethical concerns, researchers have begun exploring the use of organoids, which are small groups of cells that act like miniaturized organs, creating a simulated environment that reflects in vivo conditions. Hundreds of immune cell organoids can be constructed from the spleen of a single animal, greatly increasing testing throughput — which could help researchers keep up with the large numbers of compounds they can create and need to screen. So, Matthew DeLisa, Ankur Singh and colleagues wanted to see whether this method would provide results similar to those from animal experiments and whether the platform could be used to screen large numbers of glycoconjugate vaccine candidates.
To construct organoids, the researchers isolated B cells from mouse spleens, added cellular signaling molecules and structural components, then encapsulated everything in a synthetic hydrogel matrix. Next, they prepared conjugate vaccine candidates targeting the bacterium responsible for tularemia, or “rabbit fever,” for which an approved vaccine does not currently exist. Candidates were tested using both traditional in vivo mouse trials and the new organoid platform. The B cells reacted similarly in both formats and also provided insights into the several biochemical changes that occur as the cells mature into antibody-producing cells. As a result, the team found that the platform could be used to identify B cell clones that generate highly antigen-specific antibodies, which have a wide variety of potential applications. Though this work is preliminary, the researchers say that the organoid platform could help reduce the time it takes for new conjugate vaccines to be developed and evaluated.

Acylceramides and protein-bound ceramides are vital for the formation of the oral barrier in mice, similar to their role in skin, protecting from infection.
The skin is the body’s first line of defense against the environment, particularly against pathogens, chemicals, and allergens. It is now known that a class of biological molecules called acylceramides and their metabolites, protein-bound ceramides, are essential to the formation of this barrier. The outermost tissues of the mouth are closely related to the skin and have similar functions — an oral barrier. However, little is known about the role and importance of acylceramides and protein-bound ceramides in the oral barrier.
Associate Professor Takayuki Sassa and Professor Akio Kihara at the Faculty of Pharmaceutical Sciences, Hokkaido University, investigated the roles of acylceramides and protein-bound ceramides in the formation of the oral barrier in mice. Their findings, published in the journal Cell Reports, reveal that acylceramides and protein-bound ceramides are indispensable for the formation of the oral barrier.
“The skin and the tissues of the mouth and throat are classified as a type of tissue called stratified squamous epithelium; acylceramides and protein-bound ceramides are present in both,” Sassa explained. “These ceramides in the skin are vital as they create the permeability barrier. Hence, we were interested in investigating if they played a similar role in the formation of the oral barrier.”
Sassa and Kihara first performed liquid chromatography-tandem mass spectrometry analyses, to fully understand the types of acrylamides and protein-bound ceramides present in the mouse oral tissues. To examine the role and importance of acylceramides and protein-bound ceramides, they generated model mice, which have reduced ability to synthesize these ceramides in the oral tissues.
The tongues of mice having less acylceramides and protein-bound ceramides exhibited hyperkeratosis, the thickening of the outermost layer, often observed in the skin with barrier deficiency, and the mice were significantly more sensitive to capsaicin in drinking water, indicating that the oral barrier formation was affected.
In addition, using oral swabs collected from three volunteers, they also analyzed and cataloged the acylceramides and protein-bound ceramides present in the human oral tissues.
“We conclusively demonstrated that acylceramides and protein-bound ceramides were present in the oral tissues,” Kihara expounded. “This was highlighted in the model mice we developed for the study: due to the reduction in the amount of acylceramides and protein-bound ceramides, oral barrier formation was affected.”
While the findings of the study that acylceramides and protein-bound ceramides are vital for the formation of the oral barrier in mice, this must be confirmed in humans. In particular, the soft and hard tissues of the human mouth have different distributions of protein-bound ceramides, which may in turn affect the formation of the oral barrier at different locations.

A Yale School of Public Health study has found that older persons with mild cognitive impairment (MCI), a common type of memory loss, were 30% more likely to regain normal cognition if they had taken in positive beliefs about aging from their culture, compared to those who had taken in negative beliefs.
Researchers also found that these positive beliefs also enabled participants to recover their cognition up to two years earlier than those with negative age beliefs.This cognitive recovery advantage was found regardless of baseline MCI severity.
“Most people assume there is no recovery from MCI, but in fact half of those who have it do recover. Little is known about why some recover while others don’t. That’s why we looked at positive age beliefs, to see if they would help provide an answer,” said Becca Levy, professor of public health and of psychology and lead author of the study.
Levy predicted that positive age beliefs could play an important role in cognitive recovery because her previous experimental studies with older persons found that positive age beliefs reduced the stress caused by cognitive challenges, increased self-confidence about cognition, and improved cognitive performance.
The new study is the first to find evidence that a culture-based factor — positive age beliefs — contributes to MCI recovery. The study appeared in JAMA Network Open. Martin Slade, a biostatistician and lecturer in internal medicine at Yale, is co-author of the study.
Older persons in the positive age-belief group who started the study with normal cognition were less likely to develop MCI over the next 12 years than those in the negative age-belief group, regardless of their baseline age and physical health.
The National Institute on Aging funded this study. It had 1,716 participants aged 65 and above who were drawn from the Health and Retirement Study, a national longitudinal study.
“Our previous research has demonstrated that age beliefs can be modified; therefore, age-belief interventions at the individual and societal levels could increase the number of people who experience cognitive recovery,” Levy said.

In a large joint project, a total of six research groups from the University of Cologne Cluster of Excellence on Cellular Stress Responses in Age-Associated Diseases (CECAD), the Max Planck Institute for Biology of Aging (MPI) in Cologne and the University of Göttingen have demonstrated the following findings which apply across the animal kingdom: with increasing age, the transcriptional elongation speed of genes increases, whereby the quality of the gene products suffers. With dietary restrictions, these processes could be reversed / Publication in Nature.
Fast but sloppy, that’s how the transcription of genes changes with age. Six research groups from the University of Cologne Cluster of Excellence on Cellular Stress Responses in Age-Associated Diseases (CECAD), the Max Planck Institute for Biology of Aging (MPI) in Cologne and the University of Göttingen discovered a new molecular mechanism that contributes to ageing by studying the transcription process in five different model organisms and in a wide variety of tissues.
Ageing impairs a wide range of cellular processes, many of which affect the quality and concentration of proteins. Among these processes, the reading of genes known as transcription is particularly important, because it is a main regulator of protein levels. Although experts knew that gene expression, i.e. the conversion of genetic information into proteins, changes with age, and also that the control of gene expression may be impaired, it was unclear whether the accuracy of the transcription process itself changes with age and whether such a change would have relevant consequences for organisms.
This is exactly what the researchers have now been able to demonstrate, which makes Andreas Beyer, CECAD working group leader and professor at the Institute for Genetics of the Faculty of Mathematics and Natural Sciences at the University of Cologne, extremely happy: “This was a large, collaborative project lasting several years involving multiple teams from the CECAD cluster and other scientific institutions. Data from five species had to be generated and analysed. Only by combining our expertise was it possible to study so many species and types of data.”
In fact, the 26 scientists investigated genome-wide, age-related changes in transcription processes in nematodes, fruit flies, mice, rats and humans, including diverse tissues. And they discovered that the average speed at which the transcript grows through the attachment of RNA building blocks, the nucleotides, increased with age in all five species. Together with the higher speed of this elongation speed (Pol II speed), the researchers also observed changes in the so-called splicing, a further work step within the transcription process from the gene to the finished protein, in which the transcription product is once again shortened and cut to size.
However, the accuracy of the entire transcription process could also be controlled and reversed, for example by dietary restriction or intervention in insulin signaling — both measures that contribute to the extension of lifespan, as has been known for many years. Similarly, the lifespan of flies and the division potential of human cells lengthened when the researchers used interventions to reduce the reading speed.
Professor Beyer says: “Our results uncover fundamental molecular mechanisms underlying animal ageing and interventions to extend lifespan, providing clues as to how we might contribute to healthy ageing in the future. The fact that interventions, such as a reduced calorie intake, also have a positive effect on a healthy ageing process on the molecular level via improving the quality of gene transcription is something which we have now been able to prove quite clearly with our study.”
The study was carried out by the University of Cologne Cluster of Excellence on Cellular Stress Responses in Age-Associated Diseases (CECAD), The Max Planck Institute for Biology of Aging (MPI) in Cologne and the University of Göttingen

Human skin is home to millions of microbes. One of these microbes, Staphylococcus aureus, is an opportunistic pathogen that can invade patches of skin affected by eczema, also known as atopic dermatitis.
In a new study, researchers at MIT and other institutions have discovered that this microbe can rapidly evolve within a single person’s microbiome. They found that in people with eczema, S. aureus tends to evolve to a variant with a mutation in a specific gene that helps it grow faster on the skin.
This study marks the first time that scientists have directly observed this kind of rapid evolution in a microbe associated with a complex skin disorder. The findings could also help researchers develop potential treatments that would soothe the symptoms of eczema by targeting variants of S. aureus that have this type of mutation and that tend to make eczema symptoms worse.
“This is the first study to show that Staph aureus genotypes are changing on people with atopic dermatitis,” says Tami Lieberman, an assistant professor of civil and environmental engineering and a member of MIT’s Institute for Medical Engineering and Science. “To my knowledge, this is the most direct evidence of adaptive evolution in the skin microbiome.”
Lieberman and Maria Teresa García-Romero, a dermatologist and assistant professor at the National Institute of Pediatrics in Mexico, are the senior authors of the study, which appears today in Cell Host and Microbe. Felix Key, a former MIT postdoc who is now a group leader at the Max Planck Institute for Infection Biology, is the lead author of the paper.
Bacterial adaptation
It is estimated that between 30 and 60 percent of people carry S. aureus in their nostrils, where it is usually harmless. In people with eczema, which affects about 10 million children and 16 million adults in the United States, S. aureus often spreads to eczema patches and infects the skin.

“When there’s a break in the skin, Staph aureus can find a niche where it can grow and replicate,” Lieberman says. “It’s thought that the bacteria contribute to the pathology because they secrete toxins and recruit immune cells, and this immune reaction further damages the skin barrier.”
In this study, the researchers wanted to explore how S. aureus is able to adapt to living on the skin of eczema patients.
“These microbes normally live in the nose, and we wanted to know whether when it finds itself on atopic dermatitis skin, does it need to change to live there? And can we learn something about how these bacteria are interacting with atopic dermatitis skin from watching its evolution?” Lieberman says.
To answer those questions, the researchers recruited patients aged 5 to 15 who were being treated for moderate to severe eczema. They took samples of the microbes on their skin once a month for three months, and then again at nine months. Samples were taken from the backs of the knees and inside of the elbows (the most common sites affected by eczema), the forearms, which are usually not affected, and the nostrils.
S. aureus cells from each sample site were cultured separately to create up to 10 colonies from each sample, and once large colonies formed, the researchers sequenced the cells’ genomes. This yielded nearly 1,500 unique colonies, which enabled the researchers to observe the bacterial cells’ evolution in much greater detail than has previously been possible.

Using this technique, the researchers found that most patients maintained a single lineage of S. aureus — that is, it was very uncommon for a new strain to come in from the environment or another person and replace the existing S. aureus strain. However, within each lineage, a great deal of mutation and evolution occurred during the nine months of the study.
“Despite the stability at the lineage level, we see a lot of dynamics at the whole genome level, where new mutations are constantly arising in these bacteria and then spreading throughout the entire body,” Lieberman says.
Many of these mutations arose in a gene called capD, which encodes an enzyme necessary for synthesizing the capsular polysaccharide — a coating that protects S. aureus from recognition by immune cells. In two out of six deeply sampled patients, cells with capD mutations took over the entire S. aureus skin microbiome population, the researchers found. Other patients were colonized with strains initially lacking a functional copy of the capD, for a total of 22 percent of patients lacking capDat the end of the study. In one patient, four different mutations of capD arose independently in different S. aureus samples, before one of those variants became dominant and spread over the entire microbiome.
Targeted treatment
In tests of bacterial cells growing in a lab dish, the researchers showed that mutations to capD allowed S. aureus to grow faster than S. aureus strains with a normal capD gene. Synthesizing the capsular polysaccharide requires a lot of energy, so when cells don’t have to make it, they have more fuel to power their own growth. The researchers also hypothesize that loss of the capsule may allow the microbes to stick to the skin better because proteins that allow them to adhere to the skin are more exposed.
The researchers also analyzed nearly 300 publicly available genomes of bacteria isolated from people with and without eczema, and found that people with eczema were much more likely to have S. aureus variants that could not produce the capsular polysaccharide than people without eczema.
Eczema is usually treated with moisturizers or topical steroids, and doctors may prescribe antibiotics if it appears that the skin is infected. The researchers hope that their findings could lead to the development of treatments that lessen eczema symptoms by targeting S. aureus variants with mutations in the capsular polysaccharide.
“Our findings in this study provide clues as to how Staph aureus is evolving inside hosts and reveal some of the features that might help the bacteria to stay on the skin and generate disease versus being able to be swiped off,” García-Romero says. “In the future, S. aureus variants with mutations in the capsular polysaccharide could be a relevant target for potential treatments.”
Lieberman’s lab is now working on developing probiotics that could be used to target the capsule-negative S. aureus strains. Her lab is also studying whether S. aureus strains with capD mutations are more likely to spread to other members of an eczema patient’s household.
The research was funded by MISTI Global Seed Funds, the National Institutes of Health, the Burroughs Wellcome Fund, the Mexican Government Ministry of Taxes Program for Health Research and Technological Development, and a German Research Foundation fellowship.