A study led by researchers from Nanyang Technological University, Singapore (NTU Singapore) revealed that fine particulate matter from 1980 to 2020 was associated with approximately 135 million premature deaths globally.
In the study, premature deaths refer to fatalities that occur earlier than expected based on average life expectancy, resulting from preventable or treatable causes such as diseases or environmental factors.
The study found that the impact of pollution from fine particulate matter was worsened by climate variability phenomena such as the El Niño-Southern Oscillation, the Indian Ocean Dipole, and the North Atlantic Oscillation, and led to a 14 per cent rise in premature deaths.
The researchers explain that during such weather events, the increased temperature, changes in wind patterns, and reduced precipitation can lead to stagnant air conditions and the accumulation of pollutants in the atmosphere. These result in higher concentrations of PM2.5 particles that are particularly harmful to human health when inhaled.
Fine particulate matter, or PM2.5, refers to particulate matter 2.5 micrometres in diameter or smaller. These tiny particles come from vehicle emissions, industrial processes, and natural sources such as wildfires and dust storms.
As they are so small, PM2.5 particles can easily get into the air we breathe and penetrate deep into our lungs, leading to a range of health problems, especially for vulnerable groups like children, the elderly, and people with respiratory conditions.
The study estimated that a third of the premature deaths from 1980 to 2020 were associated with stroke (33.3 per cent); another third with ischemic heart disease (32.7 per cent), while chronic obstructive pulmonary disease, lower respiratory infections, and lung cancer made up the rest of premature deaths.

To understand how PM2.5 pollution affects mortality rates, the researchers studied satellite data from NASA on the levels of fine particulate matter in the Earth’s atmosphere. They also analysed statistics on the incidence and mortality of diseases linked to pollution from the Institute for Health Metrics and Evaluation, based in the US. Additionally, they considered information on climate patterns from the National Oceanic and Atmospheric Administration.
While previous studies have explored aspects of air quality and climate, this study had a global scope and analysed over 40 years of data. By examining how specific climate patterns affect air pollution in different regions, it offers fresh insights into the complex relationship between climate and air quality.
First author of the study, Associate Professor Steve Yim of NTU’s Asian School of the Environment and Lee Kong Chian School of Medicine (LKCMedicine), who led the study, said:”Our findings show that changes in climate patterns can make air pollution worse. When certain climate events happen, like El Niño, pollution levels can go up, which means more people might die prematurely because of PM2.5 pollution. This highlights the need to understand and account for these climate patterns when tackling air pollution to protect the health of the global population.” Assoc Prof Yim is also a Principal Investigator at NTU’s Earth Observatory of Singapore (EOS).
Study co-author Distinguished University Professor Joseph Sung, NTU’s Senior Vice President (Health and Life Sciences), and Dean of NTU’s LKCMedicine, said: “Our study highlights how climate patterns affect air pollution, and this is crucial for healthcare professionals because it directly impacts public health. The effects of climate change and the environment on human health are not lesser than those of genomics and lifestyle patterns, and they have been increasing over the past decades. By recognising these patterns, healthcare providers can better prepare for potential increases in patients seeking treatment for pollution-related ailments. Additionally, this knowledge underscores the importance of proactive measures to reduce pollution and mitigate its health impacts, ultimately helping healthcare systems manage and alleviate the burden of pollution-related illnesses on communities.”
The findings from this study, which represents an advance in understanding how environmental challenges affect the health of the global population, reflect NTU’s commitment to responding to the needs and challenges of healthy living and ageing, one of humanity’s grand challenges that the University seeks to address through its NTU 2025 strategic plan.
The study is also part of NTU’s S$50 million interdisciplinary climate research programme, the Climate Transformation Programme (CTP). Hosted by EOS and funded by Singapore’s Ministry of Education, the CTP aims to investigate climate change, develop, inspire, and accelerate knowledge-based solutions, and educate future leaders to establish the stable climate and environment necessary for a resilient and sustainable Southeast Asia.

Co-author of the study Professor Benjamin Horton, Director of Earth Observatory of Singapore, said: “Our study aligns seamlessly with NTU Singapore’s ambitious Climate Transformation Programme (CTP), which aims to tackle the pressing challenges of climate change through interdisciplinary research and collaboration. By investigating the intricate relationship between weather patterns and deadly air pollution, we contribute valuable insights that will inform evidence-based solutions and policies to safeguard public health and promote environmental resilience in Southeast Asia and beyond.” Prof Horton is also Professor in Earth Science at NTU’s Asian School of the Environment.
This study was also funded by several awards and a grant from the Ministry of Education, Singapore. It is also part of The Prudential EOS Climate Impacts Initiative, for which Prudential Services Singapore funded NTU’s EOS to conduct a two-year, two-phase study to understand better the impacts of climate change on air quality and its associated health impacts.
The study also saw participation from NTU President’s Chair in Genomics Professor Stephan Schuster, who is also Deputy Director at the Singapore Centre for Environmental Life Sciences Engineering (SCELSE). Healthcare professionals and researchers from The Chinese University of Hong Kong, Imperial College London, UK, Sun Yat-sen University, China, and Tan Tock Seng Hospital, Singapore were also involved. The findings were published in April in the peer-reviewed journal Environment International.
Assessing the interplay between climate phenomena, pollution, and deaths
This study used data from a dataset managed by NASA called MERRA-2 (Modern-Era Retrospective Analysis for Research and Applications, version 2). The dataset provides monthly information about the concentration of fine particulate matter on the Earth’s surface.
The PM2.5 data analysed for this 40-year study spans from January 1980 to December 2020 and gives detailed information about air pollution levels in specific areas.
The study looked at how changes in air quality are affected by climate patterns, such as the El Niño-Southern Oscillation, Indian Ocean Dipole, and North Atlantic Oscillation weather patterns, obtained from indices assessed by the US National Oceanic and Atmospheric Administration.
The researchers also used data from the Institute for Health Metrics and Evaluation based in the United States on global deaths and occurrences of pollution-linked diseases, which include lower respiratory infections, tracheal, bronchus, and lung cancer, chronic obstructive pulmonary disease, stroke, and ischemic heart disease.
The researchers found that 363 major air pollution episodes happened worldwide over the past four decades, with an average of nine episodes yearly. The duration of an air pollution episode ranged from two to nine months, with 2002 being the year with the highest number of air pollution episodes (15 episodes), followed by 2004 and 2006 (14 episodes each year).
The study estimated that Asia had the highest number of premature deaths attributable to PM2.5 pollution between 1980 and 2020, at 98.1 million, with China and India reaching 49.0 million and 26.1 million deaths, respectively. Pakistan, Bangladesh, Indonesia, and Japan also had significant numbers of PM2.5-attributable premature deaths, ranging from 2 to 5 million each.
The researchers estimate that the three weather phenomena simultaneously caused approximately 7,000 more global premature deaths annually, with the Indian Ocean Dipole phenomena having the largest impact on the number of deaths, followed by North Atlantic Oscillation, and then El Niño.
All three weather patterns coincided in 1994, 1997, 2002, and 2015, with the Southeast Asian region being the most vulnerable. Around 3,100 more deaths occurred in that region each year due to the higher impact of pollution worsened by the weather patterns.
Assoc Prof Yim added: “This study underscores the importance of prioritising public health when developing air quality strategies. Instead of solely focusing on pollutant levels, governments should also consider the health effects of air pollution. This means evaluating policies based on their impact on reducing pollution-related health issues, especially highlighting the need for targeted interventions to mitigate pollution during specific weather conditions.”
Prof Sung added: “As our study has shown that PM2.5 pollution could have significant health consequences, health agencies need to allocate resources accordingly. This includes ensuring that healthcare services are equipped to handle the demands related to PM2.5 pollution-related illnesses. By emphasising health outcomes in air quality management, governments can better protect public health and improve overall well-being.”
The team of researchers will be conducting more detailed studies for a deeper understanding of local air pollution patterns and further detailing the mechanisms behind how climate patterns influence the formation and reduction of PM2.5.

Scientists at the Broad Institute of MIT and Harvard have improved a gene-editing technology that is now capable of inserting or substituting entire genes in the genome in human cells efficiently enough to be potentially useful for therapeutic applications.
The advance, from the lab of Broad core institute member David Liu, could one day help researchers develop a single gene therapy for diseases such as cystic fibrosis that are caused by one of hundreds or thousands of different mutations in a gene. Using this new approach, they would insert a healthy copy of the gene at its native location in the genome, rather than having to create a different gene therapy to correct each mutation using other gene-editing approaches that make smaller edits.
The new method uses a combination of prime editing, which can directly make a wide range of edits up to about 100 or 200 base pairs, and newly developed recombinase enzymes that efficiently insert large pieces of DNA thousands of base pairs in length at specific sites in the genome. This system, called eePASSIGE, can make gene-sized edits several times more efficiently than other similar methods, and is reported in Nature Biomedical Engineering.
“To our knowledge this is one of the first examples of programmable targeted gene integration in mammalian cells that satisfies the main criteria for potential therapeutic relevance,” said Liu, who is senior author of the study, the Richard Merkin Professor and director of the Merkin Institute of Transformative Technologies in Healthcare at the Broad, a professor at Harvard University and a Howard Hughes Medical Institute investigator. “At these efficiencies, we expect that many if not most loss-of-function genetic diseases could be ameliorated or rescued, if the efficiency we observe in cultured human cells can be translated into a clinical setting.”
Graduate student Smriti Pandey and postdoctoral researcher Daniel Gao, both in Liu’s group, were co-first authors on the study, which was also a collaboration with Mark Osborn’s group at the University of Minnesota and Elliot Chaikof’s group at the Beth Israel Deaconess Medical Center.
“This system offers promising opportunities for cell therapies where it can be used to precisely insert genes into cells outside of the body before administering them to patients to treat disease, among other applications,” Pandey said.
“It’s exciting to see the high efficiency and versatility of eePASSIGE, which could enable a new category of genomic medicines,” added Gao. “We also hope that it will be a tool that scientists from across the research community can use to study basic biological questions.”
Prime improvements

Many scientists have used prime editing to efficiently install changes to DNA that are up to dozens of base pairs in length, sufficient to correct the vast majority of known pathogenic mutations. But introducing entire healthy genes, often thousands of base pairs long, in their native location in the genome has been a long-standing goal of the gene-editing field. Not only could this potentially treat many patients regardless of which mutation they have in a disease-causing gene, but it would also preserve the surrounding DNA sequences, which would increase the likelihood that the newly installed gene is properly regulated, rather than expressed too much, too little, or at the wrong time.
In 2021, Liu’s lab reported a key step towards this goal and developed a prime editing approach called twinPE that installed recombinase “landing sites” in the genome, and then used natural recombinase enzymes such as Bxb1 to catalyze the insertion of new DNA into the prime edited target sites.
The biotech company Prime Medicine, co-founded by Liu, soon began using this technology, which they called PASSIGE (prime-editing-assisted site-specific integrase gene editing), to develop treatments for genetic diseases.
PASSIGE installs edits in only a modest fraction of cells, which is enough to treat some but probably not most genetic diseases that result from the loss of a functioning gene. So Liu’s team, in the new work reported today, set out to boost PASSIGE’s editing efficiency. They found that the recombinase enzyme Bxb1 was the culprit in limiting the efficiency of PASSIGE. They then used a tool previously developed by Liu’s group called PACE (phage-assisted continuous evolution) to rapidly evolve more efficient versions of Bxb1 in the lab.
The resulting newly evolved and engineered Bxb1 variant (eeBxb1) improved the eePASSIGE method to integrate an average of 30 percent of gene-sized cargo in mouse and human cells, four times more than the original technique and about 16 times more than another recently published method called PASTE.
“The eePASSIGE system provides a promising foundation for studies integrating healthy gene copies at sites of our choosing in cell and animal models of genetic diseases to treat loss-of-function disorders,” Liu said. “We hope this system will prove to be an important step towards realizing the benefits of targeted gene integration for patients.”
With this goal in mind, Liu’s team is now working on combining eePASSIGE with delivery systems such as engineered virus-like particles (eVLPs) that may overcome hurdles that have traditionally limited therapeutic delivery of gene editors in the body.

How do pathogens invade the lungs? Using human lung microtissues, a team at the Biozentrum of the University of Basel has uncovered the strategy used by a dangerous pathogen. The bacterium targets specific lung cells and has developed a sophisticated strategy to break through the lungs’ line of defense.
Earlier this year, the WHO published a list of twelve of the world’s most dangerous bacterial pathogens that are resistant to multiple antibiotics and pose a grave threat to human health. This list includes Pseudomonas aeruginosa, a much-feared nosocomial pathogen that causes severe and life-threatening pneumonia. This pathogen is especially threatening to immunocompromised patients and those on mechanical ventilation, with mortality rates up to 50 percent.
The lung barrier is penetrable
Pseudomonas aeruginosa has developed a broad range of strategies to invade the lungs and the body. Researchers led by Prof. Urs Jenal at the Biozentrum, University of Basel, have now gained novel insights into the infection process using lab-grown lung microtissues generated from human stem cells. In the scientific journal “Nature Microbiology,” they describe how Pseudomonas breaches the top layer of lung tissue and invades deeper areas. This study was conducted as part of the National Center of Competence in Research (NCCR) “AntiResist.”
Our lungs are lined by a thin layer of tightly packed cells that protects the deeper layers of lung tissue. The surface is covered with mucus, which traps particles such as microorganisms and is removed from the airways by specialized cells. This layer serves as an effective almost impenetrable barrier against invading pathogens. However, Pseudomonas bacteria have found a way to breach it. But how the pathogen crosses the tissue barrier has remained a mystery until now.
Lung organoids provide new insight into infections in humans
“We have grown human lung microtissues that realistically mimic the infection process inside a patient’s body,” explains Jenal. “These lung models enabled us to uncover the pathogen’s infection strategy. It uses the mucus-producing goblet cells as Trojan horses to invade and cross the barrier tissue. By targeting the goblet cells, which make up only a small part of the lung mucosa, the bacteria can breach the defense line and open the gate.”
With a large arsenal of virulence factors, known as secretion systems, the pathogen specifically attacks and invades the goblet cells, replicates inside the cells and ultimately kills them. The burst of the dead cells leads to ruptures in the tissue layer, making the protective barrier leaky. The pathogens exploit this weak spot: They rapidly colonize the rupture sites and spread into deeper tissue regions.

New sensor for monitoring bacteria
Using human lung organoids, the scientists have been able to elucidate the sophisticated infection strategies of Pseudomonas. However, it remains unclear how the pathogens adapt their behavior during the infection process. For example, they must first be mobile to spread over the tissue surface, then quickly adhere to lung cells upon contact, and later activate their virulence factors. It is known that the bacteria can rapidly change their behavior thanks to small signaling molecules. Until now, however, the technology to study these correlations was not available.
Jenal’s team has now developed a biosensor to measure and track a small signaling molecule called c-di-GMP in individual bacteria. The method was recently described in Nature Communications. “This is a technological breakthrough,” says Jenal. “Now we can monitor in real time and with high resolution how this signaling molecule is regulated during infection and how it controls the pathogen’s virulence. We now have a detailed view on when and where individual bacterial cells activate certain programs to regulate their behavior. This method enables us to investigate lung infections in more detail.”
Organ models mimic conditions in patients
“Thanks to the development of human lung organoids, we now have a much better understanding of how the pathogens behave in human tissue and presumably in patients,” emphasizes Jenal. “This brings us a big step closer to the goal of NCCR AntiResist.” Organoids of the human lung and other organs like the bladder allow the researchers to study the effects of antibiotics in tissue, for example, identifying where and how bacteria survive during treatment. Such organ models will be indispensable in the future for developing new and effective strategies to combat pathogens.

Academics are often accused of “splitting hairs,” but a team at Trinity College Dublin has now devised a machine to do just that. We all have a bad hair day from time to time, and split ends are a common problem. However, the science behind this kind of hair damage is poorly understood, which is why the Trinity team, led by Professor David Taylor, is investigating this knotty problem.
Prof. Taylor’s research in the Trinity Centre for Biomedical Engineering covers all kinds of natural materials, from human bone to seashells but he had never worked on hair. So, when leading cosmetics company L’Oreal approached him, he was happy to accept the challenge.
Working with colleagues, he developed the “Moving Loop Fatigue machine,” which has been expertly designed to recreate what happens when tangled hair is combed out. The results have just been published in theJournal of the Royal Society Interface Focus.
Two types of hair were tested: some from a person who suffered from split ends and some from a person who didn’t. Using the machine, the team was able to generate splits in both types of hair, but the splitting-prone hair split more quickly and generated splits that were much longer. Additionally, when bleached, the hair from the person who didn’t suffer with split ends started to split similarly to the splitting-prone sample.
Isobel Duffy, one of the researchers on the team, added: “We were amazed at how well the machine worked — often, a single strand of hair split into two along its whole length, in the same way that hair does when some people dry and comb it before starting their days. Now we can create splits in a reproducible way we can go on to study why some people’s hair splits and some doesn’t, and better investigate the effects that some cosmetic treatments have on hair quality.”
Prof. David Taylor said: “This work constitutes a first step in developing a scientific approach to better understanding the biomechanics of hair splitting. It paves the way for future studies, including a more comprehensive experimental programme involving a larger number of donors with different hair types — including curly hair — and more detailed studies that could incorporate the effects of humidity, temperature and different treatments.
“Hair is a complex material and it is surprising how little we know about it. In time our work may change that, with implications for the cosmetics industry and the millions of people across the globe that want to take first-rate care of their hair.”
Another team member, Robert Teeling, added: “When I started as an Engineering student in Trinity I didn’t think I would spend my Masters’ year testing hair. But it turned out to be a great project: I designed and built a new type of machine from scratch and made a real contribution to science. I learnt that hair is a material like any other: it can break through mechanical forces, in this case when you comb or brush it, and it’s sensitive to how you treat it.”

People who eat a healthy, sustainable diet may substantially lower their risk of premature death in addition to their environmental impact, according to a new study led by Harvard T.H. Chan School of Public Health. It is the first large study to directly evaluate the impacts of adherence to recommendations in the landmark 2019 EAT-Lancet report. The researchers have named the dietary pattern outlined in the report — which emphasizes a variety of minimally processed plant foods but allows for modest consumption of meat and dairy foods — the Planetary Health Diet (PHD).
The study will be published online June 10 in The American Journal of Clinical Nutrition.
“Climate change has our planet on track for ecological disaster, and our food system plays a major role,” said corresponding author Walter Willett, professor of epidemiology and nutrition. “Shifting how we eat can help slow the process of climate change. And what’s healthiest for the planet is also healthiest for humans.”
While other studies have found that diets emphasizing plant-based foods over animal-sourced foods could have benefits for human and planetary health, most have used one-time dietary assessments, which produce weaker results than looking at diets over a long period of time.
The researchers used health data from more than 200,000 women and men enrolled in the Nurses’ Health Study I and II and the Health Professionals Follow-Up Study. Participants were free of major chronic diseases at the start of the study and completed dietary questionnaires every four years for up to 34 years. Participants’ diets were scored based on intake of 15 food groups — including whole grains, vegetables, poultry, and nuts — to quantify adherence to the PHD.
The study found that the risk of premature death was 30% lower in the top 10% of participants most closely adhering to PHD compared to those in the lowest 10%. Every major cause of death, including cancer, heart disease, and lung disease, was lower with greater adherence to this dietary pattern.
In addition, the researchers found that those with the highest adherence to the PHD had a substantially lower environmental impact than those with the lowest adherence, including 29% lower greenhouse gas emissions, 21% lower fertilizer needs, and 51% lower cropland use.

The researchers noted that land use reduction is particularly important as a facilitator of re-forestation, which is seen as an effective way to further reduce levels of greenhouse gases that are driving climate change.
“Our study is noteworthy given that the U.S. Department of Agriculture has refused to consider the environmental impacts of dietary choices, and any reference to the environmental effects of diet will not be allowed in the upcoming revision of the U.S. Dietary Guidelines,” said Willett. “The findings show just how linked human and planetary health are. Eating healthfully boosts environmental sustainability — which in turn is essential for the health and wellbeing of every person on earth.”
Other Harvard Chan School authors included Linh Bui, Fenglei Wang, Qi Sun, Frank Hu, Kyu Ha Lee, and Marta Guasch-Ferre.
The study was funded by National Institutes of Health (NIH) research grants UM1 CA186107, P01 CA87969, R01 HL034594, U01 CA176726, U01 CA167552, R01 HL035464, R01 DK120870, and R01 DK126698.
“Planetary Health Diet Index and risk of total and cause specific mortality in three prospective cohorts,” Linh P. Bui, Tung T. Pham, Fenglei Wang, Boyang Chai, Qi Sun, Frank B. Hu, Kyu Ha Lee, Marta Guasch-Ferre, Walter C. Willett, The American Journal of Clinical Nutrition, June 10, 2024, doi: 10.1016/j.ajcnut.2024.03.019

A clinical trial on a two-drug therapy for methamphetamine use disorder reduced use of the highly addictive drug for up to 12 weeks after initiation of treatment, UCLA-led research suggests.
Participants in the ADAPT-2 clinical trial who received a combination of injectable naltrexone plus extended-release oral bupropion (NTX+BUPN) had a 27% increase in methamphetamine-negative urine tests, indicating reduced usage. By contrast, the placebo group had an 11% increase in negative tests.
The study will be published in the peer-reviewed journal Addiction.
“These findings have important implications for pharmacological treatment for methamphetamine use disorder. There is no FDA-approved medication for it, yet methamphetamine-involved overdoses have greatly increased over the past decade,” said Dr. Michael Li, assistant professor-in-residence of family medicine at the David Geffen School of Medicine at UCLA and the study’s lead author.
Methamphetamine use has continued growing over the years around the world, increasing from 33 million people in 2010 to 34 million in 2020. Overdose deaths from the drug have jumped fivefold in the US from 2012 to 2018, and are followed by Canada and Australia in increases.
To curb the ongoing crisis, the National Institute on Drug Abuse (NIDA) Clinical Trials Network has supported various trials, including the ADAPT-2 trial, to test the effects of different pharmacological treatments for methamphetamine use disorder. ADAPT-2 was carried out from May 23, 2017 to July 25, 2019 across the eight trial sites that included UCLA. It included 403 participants, with 109 assigned to the drug combo group and the rest to the placebo group in the first stage.
The latest findings are the second stage of the multi-site trial. The earlier stage had demonstrated that the two-drug combination worked at six weeks, but the unanswered question was whether the intervention remained efficacious over a longer period.

In the second stage, the researchers conducted urine tests on the participants at weeks seven and 12, and again post-treatment at weeks 13 and 16 comparing the group on NTX+BUPN with the placebo group.
There is a need for further research to determine whether the drug treatment effect lasts longer than 12 weeks and yields further methamphetamine use reductions, the researchers write.
“Prior stimulant use disorder treatment trials suggest that change in use is gradual (consistent with our findings), unlikely to result in sustained abstinence in a typical 12-week trial, and dependent on treatment duration,” they write. “This warrants future clinical trials to quantify changes in MA use beyond 12 weeks and to identify the optimal duration of treatment with this medication.”
Study co-authors are Brendon Chau, Thomas Belin, and Steven Shoptaw of UCLA, and Thomas Carmody, Manish Jha, Elise Marino, and Dr. Madhukar Trivedi of the University of Texas.
The study was funded by awards from the National Institute on Drug Abuse of the U.S. National Institutes of Health (UG1DA020024, K01DA051329, UG1DA013035, UG1DA040316, UG1DA013727, and UG1DA015815), the U.S. Department of Health and Human Services under contract numbers HHSN271201500065C (Clinical Coordinating Center, the Emmes Company) and HHSN271201400028C (Data and Statistics Center, the Emmes Company), the U.S. National Institute of Mental Health (K23MH126202) and the O’Donnell Clinical Neuroscience Scholar Award from the University of Texas, Southwestern Medical Center.

When scientists transplanted the gut microbes of aged mice into young “germ-free” mice — raised to have no gut microbes of their own — the recipient mice experienced an increase in inflammation that parallels inflammatory processes associated with aging in humans. Young germ-free mice transplanted with microbes from other young mice had no such increase.
The findings suggest that changes to the gut microbiome play a role in the systemwide inflammation that often occurs with aging, the researchers said.
Reported in the journal Aging Cell, the study also found that antibiotics caused longer-lasting disruptions in the gut microbiomes of aged mice than in young mice.
“There’s been a growing consensus that aging is associated with a progressive increase in chronic low-grade inflammation,” said Jacob Allen, a professor of kinesiology and community health at the University of Illinois Urbana-Champaign who led the new research with Thomas Buford, a professor of medicine at the University of Alabama at Birmingham. “And there’s a kind of debate as to what drives this, what is the major cause of the aging-induced inflammatory state. We wanted to understand if the functional capacity of the microbiome was changing in a way that might contribute to some of the inflammation that we see with aging.”
Previous studies have found associations between age-related changes in the microbial composition of the gut and chronic inflammatory diseases such as Parkinson’s disease and Alzheimer’s disease. Some studies have linked microbial metabolism to an individual’s susceptibility to other health conditions, including obesity, irritable bowel syndrome and heart disease. Age-related changes in the gut microbiome also may contribute to the so-called leaky gut problem, the researchers said.
“Microbiome patterns in aged mice are strongly associated with signs of bacterial-induced barrier disruption and immune infiltration,” they wrote.
“The things that are in our gut are supposed to be kept separate from the rest of our system,” Buford said. “If they leak out, our immune system is going to recognize them. And so then the question was: ‘Is that a source of inflammation?'”
Many studies have compared the relative abundance and diversity of species of microbes in the gut, offering insight into some of the major groups that contribute to health or disease. But sequencing even a portion of the microbes in the gut is expensive and the results can be difficult to interpret, Allen said. That is why he and his colleagues focused on microbial function — specifically, how the gut microbiomes of aging mice might spur an immune response.

The team focused on toll-like receptors, molecules that mediate inflammatory processes throughout the body. TLRs sit in cellular membranes and sample the extracellular environment for signs of tissue damage or infection. If a TLR encounters a molecule associated with a potential pathogen — for example, a lipopolysaccharide component of a gram-negative bacterium — it activates an innate immune response, calling in pro-inflammatory agents and other molecules to fight the infection.
The researchers first evaluated whether the colonic contents of young and aged mice were likely to promote TLR signaling. They found that microbes from aged mice were more likely than those from young mice to activate TLR4, which can sense lipopolysaccharide components of bacterial cell walls. A different receptor, TLR5, was not affected differently in aged or young mice. TLR5 senses a different bacterial component, known as flagellin.
Young germ-free mice transplanted with the microbes of aged mice also experienced higher inflammatory signaling and increased levels of lipopolysaccharides in the blood after the transplants, the team found.
This finding provides “a direct link between aging-induced shifts in microbiota immunogenicity and host inflammation,” the researchers wrote.
In other experiments, the team treated mice with broad-spectrum antibiotics and tracked changes in the microbiomes during treatment and for seven days afterward.
“One of the most interesting questions for me was what microbes come back immediately after the treatment with antibiotics ends,” Buford said. And in the mice with aged microbiota in their guts, “these opportunistic pathogens were the most quick to come back.”
“It appears that as we age our microbiome might be less resilient to antibiotic challenges,” Allen said. “This is important because we know that in the U.S. and other Western societies, we’re increasingly exposed to more antibiotics as we age.”

The study is an important step toward understanding how age-related microbial changes in the gut may affect long-term health and inflammation, the researchers said.
Coauthors of the study also included Illinois postdoctoral researcher Elisa Caetano-Silva; U. of I. Ph.D. student Akriti Shrestha; National Children’s Hospital research scientist Michael Bailey; and Jeffrey Woods, the director of the Center on Health, Aging and Disability at Illinois.
Allen also is a professor of nutritional sciences at Illinois and an affiliate of the Carl R. Woese Institute for Genomic Biology at the U. of I.
The National Institutes of Health supported this research.

The COVID-19 pandemic resulted in over 700 million infections and 7 million deaths worldwide. While age is recognized as a risk factor for severe COVID-19, the reasons for this are not yet fully understood.
A new study by researchers at Boston University Chobanian & Avedisian School of Medicine suggests that the immune response of lung endothelial cells, which line the blood vessels, is too low during the early stage of COVID-19 infection as demonstrated in a preclinical model. Additionally, the researchers analyzed all genes expressed in purified endothelial cells, which had never been done before.
“The susceptibility to SARS-CoV-2 infection increases proportionally with age, placing older individuals at a significantly higher risk of developing severe COVID-19. Therefore, gaining insight into age-dependent pathological changes during SARS-CoV-2 infection is imperative for effectively safeguarding vulnerable populations,” said corresponding author Markus Bosmann,MD,associate professor of medicine, pathology & laboratory medicine at the school.
The researchers used four groups of endothelial cell conditions with susceptibility to SARS-CoV-2. The first two groups, consisting of young and old models, remained uninfected as controls. The other two groups, also young and old, were infected with SARS-CoV-2. Endothelial cells from all sets of conditions were isolated after two days, and their transcriptomes (their expressed genes) were analyzed and classified as biological programs of the host response. The clinical severity of infection was monitored and found to be more severe with advanced age.
According to Bosmann, a suppressed immune landscape is a key driver of age-associated endothelial dysfunction during COVID-19. “While these findings currently do not have immediate implications for treating COVID-19, targeting these immune pathways in endothelial cells may have prognostic and therapeutic benefits although further studies, including dissecting these functional changes at a single-cell level, are needed,” he adds.
These findings appear online in the journal Frontiers in Immunology.

Immune activation in a pregnant woman can have negative effects on the development of fetal brain microglia — or macrophage immune cells in the brain — and even lead to neurodevelopmental disorders in newborns.
It’s not possible to monitor how microglia are developing within the fetal brain, but new research indicates that the health of fetal macrophages in the placenta can act as an indicator of the health of fetal brain microglia.
The research was led by investigators from Massachusetts General Hospital, a founding member of the Mass General Brigham healthcare system, and is published in Cell Reports.
“If we can use fetal placental macrophages as a surrogate cell type or biomarker for fetal brain microglial programming, we have the opportunity to identify those children at greatest risk from in utero immune-activating exposures. Identifying these children early creates the potential to intervene during key developmental windows to ameliorate the impact of those pregnancy exposures,” said senior author Andrea Edlow, MD MSc, an associate professor of Obstetrics, Gynecology, and Reproductive Biology, and a Maternal-Fetal Medicine specialist at Massachusetts General Hospital. Dr. Edlow is also an MGH Research Scholar.
Examples of immune-activating exposures during pregnancy include bacterial and viral infections, metabolic inflammation from obesity and diabetes, environmental toxins and maternal stress. Edlow and her colleagues assessed placental macrophages in a mouse model of maternal diet-induced obesity.
Single-cell RNA sequencing of mouse fetal placental macrophages (or Hofbauer cells) revealed similar gene expression signatures as fetal brain microglia during normal conditions and also in response to maternal diet-induced obesity.
Interestingly, the sex of the fetus impacted how maternal obesity affects the placenta and the fetal brain. Specifically, male placental macrophages and fetal brain microglia had a greater number of genes dysregulated by maternal obesity and more neuroinflammatory signaling than female cells.
When the investigators compared their mouse data with published human datasets, they found conserved gene expression patterns in placental macrophages in mice and humans, suggesting that their findings in mice may have clinical implications in humans.
“This work is a promising start for using fetal placental macrophages as a biomarker for fetal brain microglial programming in a variety of maternal exposures, and it could form the basis for creating personalized fetal models of neurodevelopment using cells from the placenta that are easily accessible at birth,” said Edlow.

After women go through menopause, their risk of heart disease increases dramatically. To improve and support heart and blood vessel health among postmenopausal women, researchers at Penn State studied whether beetroot juice can improve how blood vessels function. Results published today (June 10) in Frontiers in Nutrition indicated that daily consumption of beetroot juice by postmenopausal women may improve blood vessel function enough to reduce future heart disease risk.
Beetroot juice contains high levels of nitrate, which the body converts to nitric oxide. Nitric oxide helps blood vessels expand, making it easier for blood to flow through the circulatory system. The ability of nitric oxide to widen blood vessels is known to be particularly helpful during periods of limited blood flow and oxygen delivery, such as during a heart attack, according to the researchers.
David Proctor, professor of kinesiology and physiology at Penn State, and Jocelyn Delgado Spicuzza, who earned her doctorate in integrative and biomedical physiology from Penn State in May, led an interdisciplinary team of researchers who tested how nitrate-rich beetroot juice impacted blood vessel health in 24 postmenopausal women in their 50s and 60s.
“After menopause, women no longer produce estrogen, which helps maintain nitric oxide in the body,” said Delgado Spicuzza, first author of the research and current SAFE-T center research project manager. “This loss of nitric oxide production contributes to the substantial increase in heart disease risk for postmenopausal women. Foods that are rich in nitrate — especially beets — are being investigated as a natural, non-pharmaceutical way to protect the heart and blood vessels.”
Nitrate is an approved food additive for some animal-based food products, such as processed meats. However, nitrate food additives and preservatives are strictly regulated due to their potential to cause cancer, according to Delgado Spicuzza. In contrast, plants like beets, spinach and lettuce naturally accumulate nitrate from the soil. These plant-based sources of nitrate have cardiovascular benefits because the human body can convert nitrates from plants to nitric oxide, which it cannot do with nitrate added to meats.
In this study, participants had their vascular function tested at the Penn State Clinical Research Center and then consumed two 2.3-ounce bottles of beetroot juice as an initial dose, followed by one bottle every morning for a week. All participants consumed concentrated beetroot juice, with each serving providing as much nitrate as three large beets. A few weeks later, the participants drank beetroot juice with the nitrate removed.
Neither the researchers nor the participants knew which juice was being consumed at the time of testing. A day after their last dose, participants returned for testing of their vascular function. The researchers compared how well blood vessels expanded for each woman when they were and were not consuming the nitrate-rich beetroot juice.

The researchers used an ultrasound sensor to monitor how blood flowed through the brachial artery — which is in the upper arm and supplies blood to the hands — during a stress test in which blood flow was restricted in each participant’s forearm for five minutes. When the restriction was removed, researchers measured how blood flow changed in the brachial artery again.
The results showed that consumption of nitrate-rich beetroot juice each day improved blood flow compared to when the participants drank nitrate-free beetroot juice. The researchers said that this level of improved blood-vessel function — if it could be maintained over the postmenopausal years — could significantly reduce the risk of heart disease. They said that long-term health benefits of beetroot juice have not been studied at this point, but the long-term benefits of nitrate-rich vegetables have been confirmed.
“Women may need to consume beetroot juice daily — or even more often — to experience all of the potential cardiovascular benefits,” Proctor said. “Still, this research shows that beetroot juice can be very useful in protecting blood vessel health of mid-life women during a period of accelerating heart disease risk.”
This study included women considered early postmenopausal, or one to six years post-menopause, and late postmenopausal, six or more years post-menopause. Late postmenopausal women saw the same benefits as the early postmenopausal group.
Delgado Spicuzza said the research team was particularly excited to find that beetroot juice improved blood vessel health for women who had gone through menopause years earlier. Some treatments for protecting cardiovascular health in postmenopausal women — like hormone therapy — are only safe during the first several years post-menopause. After that, hormone therapy can increase the risk of cancers and stroke.
“Some clinicians are already recommending beetroot juice to men and women with high blood pressure,” Delgado Spicuzza said. “By providing a safe and effective way to improve blood vessel function, beets could help maintain cardiovascular health in postmenopausal women. When you consider that most women are postmenopausal for at least a third of their lives, you can begin to understand the potential significance of these results.”
Delgado Spicuzza won the Mid-Atlantic American College of Sports Medicine 2023 Doctoral Student Investigator Award for her presentation on this research in fall of 2023. She said it is gratifying to see this research resonate with other researchers and especially with the women in the study, who seemed to embrace the potential of beetroot juice.

“Several of the participants said that they intended to continue consuming beetroot juice after the study concluded,” she said. “There seems to be a real desire on the part of postmenopausal women to support their cardiovascular health without taking additional medications. In part, I believe beets can be a complementary food to improve blood vessel health in millions of women as they age.”
Jigar Gosalia, graduate student in kinesiology at Penn State; Mary Jane De Souza, distinguished professor of kinesiology and physiology at Penn State; Kristina Petersen, associate professor of nutritional sciences at Penn State; Michael Flanagan, doctor of family medicine at Penn State Health; Liezhou Zhong, postdoctoral research fellow in the School of Medical and Health Science at Edith Cowan University in Australia; Catherine Bondonno, senior research fellow in the School of Medical and Health Science at Edith Cowan University in Australia; Elmira Alipour, clinical research coordinator at Atrium Health Carolinas Medical Center; Daniel Kim-Shapiro, professor of physics and Harbert Family Distinguished Chair for Excellence in Teaching and Scholarship at Wake Forest University; and Yasina Somani, assistant professor of exercise physiology at the University of Leeds in the United Kingdom, all contributed to this research.
The researchers said they are grateful to Cyndi Flanagan and Christa Oelhaf, nurses in the Clinical Research Center, for their contributions to this research.
This research was funded by the National Institutes of Health and the Huck Endowment for Nutritional Research in Family and Community Medicine at Penn State College of Medicine and University Park.