An exhaustive four year-long study has shown that metformin reduces the effect of ageing. Using a wide array of ageing indicators, the researchers found that metformin resulted in about six year regression in brain ageing. They reported their findings in Cell.
Prior research and anectodal evidence suggested that metformin had an anti-ageing effect. Given to flies, worms and rodents, the drug showed evidence of rejuvenation. People taking metformin also reported feeling younger the longer they took it for.
In a rigorous 40-month study, the researchers gave metformin to 12 elderly male cynomolgus macaques and 18 other cynomolgus monkeys the drug daily. They were aged 13–16 years, equivalent to 40–50 in human years. A control group was used, as well as middle-aged and younger controls to account for ageing effects.
The study encompassed a comprehensive suite of physiological, imaging, histological, and molecular evaluations, substantiating metformin’s influence on delaying age-related phenotypes at the organismal level.
Tissue samples were taken at regular intervals, we leveraged pan-tissue transcriptomics, DNA methylomics, plasma proteomics, and metabolomics to develop innovative monkey aging clocks and applied these to gauge metformin’s effects on ageing.
The results highlighted a significant slowing of aging indicators. A number of organs that seemed to benefit included the kidneys, lungs and the skin. The greatest effect was seen in the brain, however. Metformin exerts a substantial neuroprotective effect, preserving brain structure and enhancing cognitive ability. In this case, treated monkeys had brain activity comparable to those six years younger.
The geroprotective effects on primate neurons were partially mediated by the activation of Nrf2, a transcription factor with anti-oxidative capabilities. The researchers say that this work pioneers the systemic reduction of multi-dimensional biological age in primates through metformin, paving the way for advancing pharmaceutical strategies against human aging.
The researchers have also started a much larger phase 2 human trial, with 120 participants.
Cannabis use may lead to thinning of the cerebral cortex in adolescents according to a recent study. The study demonstrates that THC – or tetrahydrocannabinol, an active substance in cannabis – causes shrinkage of the dendritic arborisation, neurons’ “network of antennae” whose role is critical for communication between neurons. This results in the atrophy of certain regions of the cerebral cortex – bad news at an age when the brain is maturing.
“If we take the analogy of the brain as a computer, the neurons would be the central processor, receiving all information via the synapses through the dendritic network,” explains Tomas Paus, who is also a professor of psychiatry and neuroscience at Université de Montréal. “So a decrease in the data input to the central processor by dendrites makes it harder for the brain to learn new things, interact with people, cope with new situations, etc. In other words, it makes the brain more vulnerable to everything that can happen in a young person’s life.”
A multi-level approach to better understand the effect on humans
This project is notable for the complementary, multi-level nature of the methods used. “By analysing magnetic resonance imaging (MRI) scans of the brains of a cohort of teenagers, we had already shown that young people who used cannabis before the age of 16 had a thinner cerebral cortex,” explains Tomas Paus. “However, this research method doesn’t allow us to draw any conclusions about causality, or to really understand THC’s effect on the brain cells.”
Given the limitations of MRI, the introduction of the mouse model by Graciela Pineyro’s team was key. “The model made it possible to demonstrate that THC modifies the expression of certain genes affecting the structure and function of synapses and dendrites,” explains Graciela Pineyro, who is also a professor in the Department of Pharmacology and Physiology at Université de Montréal. “The result is atrophy of the dendritic arborescence that could contribute to the thinning observed in certain regions of the cortex.”
Interestingly, these genes were also found in humans, particularly in the thinner cortical regions of the cohort adolescents who experimented with cannabis. By combining their distinct research methods, the two teams were thus able to determine with a high degree of certainty that the genes targeted by THC in the mouse model were also associated to the cortical thinning observed in adolescents.
With cannabis use on the rise among North American youth, and commercial cannabis products containing increasing concentrations of THC, it’s imperative that we improve our understanding of how this substance affects brain maturation and cognition. This successful collaborative study, involving cutting-edge techniques in cellular and molecular biology, imaging and bioinformatics analysis, is a step in the right direction for the development of effective public health measures.
In research published in Environmental Toxicology & Chemistry, investigators sampled water from 19 locations across the Hudson and East Rivers in 2021 and 2022 to identify and quantify the prescribed pharmaceuticals and drugs of abuse that are making their way into New York City’s rivers and to determine the source of these pollutants.
Metoprolol and atenolol (blood pressure medications), benzoylecgonine (the main metabolite of cocaine), methamphetamine (a stimulant), and methadone (an opioid) were the most prevalent drugs, present in more than 60% of water samples.
More drugs and higher concentrations were detected in water contaminated by Enterococci (bacteria that live in the intestinal tract) and after rainfall, indicating an impact from sewer overflow. However, the presence of drugs in clean water and during periods of dry weather indicated that wastewater treatment plant discharge may also contribute to the presence of drugs in rivers.
“This study shows how pharmaceuticals and drugs of abuse enter the New York City aquatic environment, highlighting the necessity of improving the current water management system,” said corresponding author Marta Concheiro-Guisan, PharmD, PhD, of the John Jay College of Criminal Justice.
During missions into outer space, galactic cosmic radiation (GCR) will penetrate current spacecraft shielding and thus pose a significant risk to human health. Previous studies have shown that GCR can cause short-term cognitive deficits in male rodents. Now a study published in the Journal of Neurochemistry reveals that GCR exposure can also cause long-lasting learning deficits in female rodents.
The impact of GCR on cognition was lessened when mice were fed an antioxidant and anti-inflammatory compound called CDDO-EA.
Beyond its immediate implications for space exploration, the findings contribute to a broader understanding of radiation’s long-term impact on cognitive health.
“Our study lays the groundwork for future causal delineation of how the brain responds to complex GCR exposure and how these brain adaptations result in altered behaviours,” said co-corresponding author Sanghee Yun, PhD, of the Children’s Hospital of Philadelphia Research Institute and the University of Pennsylvania Perelman School of Medicine.
The neurons of the brain are protected by an insulating layer called myelin. In certain diseases like multiple sclerosis, the protective myelin layer around neurons is damaged and lost, leading to death of neurons and disability. New research published in The FEBS Journal reveals the importance of a protein called C1QL1 for promoting the replacement of the specialised cells that produce myelin. The findings could have important implications for the ongoing effort to develop new and improved therapies for the treatment of demyelinating diseases.
In experiments conducted in mice, deleting the gene that codes for C1QL1 caused a delay in the rate at which oligodendrocytes (the cells that make myelin) mature, leading to reduced myelination of neurons.
After mice were fed a drug that destroys myelin, recovery of oligodendrocytes and myelination were delayed in mice lacking the C1QL1 protein. Causing mice to express more C1QL1, however, led to increased numbers of oligodendrocytes and more myelination upon drug withdrawal, suggesting that C1QL1 helps to restore the damaged myelin layer. Thus, investigational therapies that boost C1QL1 may hold promise against demyelinating diseases.
“Our basic research on C1QL1 is nascent, but there is potential that it is relevant for a novel treatment for multiple sclerosis,” said corresponding author David C. Martinelli, PhD, of the University of Connecticut Health Center. “New drug treatment options for patients with multiple sclerosis could have a large impact on their quality of life.”
Long term exposure to arsenic in water may increase cardiovascular disease and especially heart disease risk even at exposure levels below the US regulatory limit (10µg/L) according to a new study in Environmental Health Perspectives. This is the first study to describe exposure-response relationships at concentrations below the current regulatory limit and substantiates that prolonged exposure to arsenic in water contributes to the development of ischaemic heart disease.
The researchers, from Columbia University Mailman School of Public Health, compared various time windows of exposure, finding that the previous decade of water arsenic exposure up to the time of a cardiovascular disease event contributed the greatest risk.
“Our findings shed light on critical time windows of arsenic exposure that contribute to heart disease and inform the ongoing arsenic risk assessment by the EPA. It further reinforces the importance of considering non-cancer outcomes, and specifically cardiovascular disease, which is the number one cause of death in the US and globally,” said Danielle Medgyesi, a doctoral Fellow in the Department of Environmental Health Sciences at Columbia Mailman School. “This study offers resounding proof of the need for regulatory standards in protecting health and provides evidence in support of reducing the current limit to further eliminate significant risk.”
According to the American Heart Association and other leading health agencies, there is substantial evidence that arsenic exposure increases the risk of cardiovascular disease. This includes evidence of risk at high arsenic levels (> 100µg/L) in drinking water. The U.S. Environmental Protection Agency reduced the maximum contaminant level (MCL) for arsenic in community water supplies (CWS) from 50µg/L to 10µg/L beginning in 2006. Even so, drinking water remains an important source of arsenic exposure among CWS users. The natural occurrence of arsenic in groundwater is commonly observed in regions of New England, the upper Midwest, and the West, including California.
To evaluate the relationship between long-term arsenic exposure from CWS and cardiovascular disease, the researchers used statewide healthcare administrative and mortality records collected for the California Teachers Study cohort from enrollment through follow-up (1995-2018), identifying fatal and nonfatal cases of ischemic heart disease and cardiovascular disease. Working closely with collaborators at the California Office of Environmental Health Hazard Assessment (OEHHA), the team gathered water arsenic data from CWS for three decades (1990-2020).
The analysis included 98 250 participants, 6119 ischaemic heart disease cases and 9,936 CVD cases. Excluded were those 85 years of age or older and those with a history of CVD at enrolment. Similar to the proportion of California’s population that relies on CWS (over 90%), most participants resided in areas served by a CWS (92%). Leveraging the extensive years of arsenic data available, the team compared time windows of relatively short-term (3-years) to long-term (10-years to cumulative) average arsenic exposure. The study found decade-long arsenic exposure up to the time of a cardiovascular disease event was associated with the greatest risk, consistent with a study in Chile finding peak mortality of acute myocardial infarction around a decade after a period of very high arsenic exposure. This provides new insights into relevant exposure windows that are critical to the development of ischemic heart disease.
Nearly half (48%) of participants were exposed to an average arsenic concentration below California’s non-cancer public health goal < 1 µg/L. In comparison to this low-exposure group, those exposed to 1 to < 5 µg/L had modestly higher risk of ischaemic heart disease, with increases of 5 to 6%. Risk jumped to 20% among those in the exposure ranges of 5 to < 10 µg/L (or one-half to below the current regulatory limit), and more than doubled to 42% for those exposed to levels at and above the current EPA limit ≥ 10µg/L. The relationship was consistently stronger for ischemic heart disease compared to cardiovascular disease, and no evidence of risk for stroke was found, largely consistent with previous research and the conclusions of the current EPA risk assessment.
These results highlight the serious health consequences not only when community water systems do not meet the current EPA standard but also at levels below the current standard. The study found a substantial 20% risk at arsenic exposures ranging from 5 to < 10 µg/L which affected about 3.2% of participants, suggesting that stronger regulations would provide significant benefits to the population. In line with prior research, the study also found higher arsenic concentrations, including concentrations above the current standard, disproportionally affect Hispanic and Latina populations and residents of lower socioeconomic status neighbourhoods.
“Our results are novel and encourage a renewed discussion of current policy and regulatory standards,” said Tiffany Sanchez, senior author. “However, this also implies that much more research is needed to understand the risks associated with arsenic levels that CWS users currently experience. We believe that the data and methods developed in this study can be used to bolster and inform future studies and can be extended to evaluate other drinking water exposures and health outcomes.”
A new study from Karolinska Institutet and the Chinese Academy of Medical Sciences has identified an RNA molecule that is important for skin wound healing. The research, published in Nature Communications, may have implications for the treatment of hard-to-heal wounds.
The study focuses on the molecular processes in wound healing that regulate the transition from inflammation to a proliferative phase, where new cells form to repair damaged tissue. Researchers have now mapped lncRNA (long non-coding RNA molecules) in human skin wounds in tissue samples from Karolinska University Hospital, identifying a key regulator in wound healing.
“Our study reveals that the lncRNA molecule SNHG26 plays a pivotal role in guiding skin cells through the stages of wound healing, from an inflammatory stage to a healing phase,” explains Ning Xu Landén, docent at the Department of Medicine, Solna, Karolinska Institutet.
The researchers also used mouse models to uncover how this molecule interacts with genes involved in inflammation and tissue regeneration. In mice lacking SNHG26, wound healing was delayed, emphasising the molecule’s importance in the balance between inflammation and tissue repair. The discovery paves the way for new therapeutic approaches for acute and chronic wounds.
“By targeting SNHG26, we may be able to accelerate healing and reduce complications, particularly in chronic wounds where prolonged inflammation is a major problem,” says Ning Xu Landén.
In a recently published study, researchers at the Institute for Environmental Medicine (IMM), Karolinska Institutet show that there are pronounced sex differences in the incidence rates of psychiatric disorders over the lifespan, which varied depending on age, type of psychiatric disorders, calendar period, and socioeconomic status.
Psychiatric disorders are among the most pressing global public health concerns. The sex difference in psychiatric disorders is among the most robust finding in psychiatry. For example, males have a higher risk of neurodevelopmental disorders, while females are more prone to depression and anxiety disorders. However, most of the evidence were based on prevalence studies, without differentiating new-onset (incident) cases from prevalent and recurrent cases, which may not inform optimal time windows for screening and interventions to reduce sex differences. There is research gap on sex differences in incident psychiatric disorders over the lifespan.
By using the nationwide Swedish register data and adopting a life-course approach, the researchers at IMM and collaborators from MEB, Uppsala University, Oslo University Hospital, and University of Iceland, have been able to depict a comprehensive atlas of sex differences in the incidence rates of clinically diagnosed psychiatric disorders over the lifespan, with an emphasis on analyzing sex differences by various types of psychiatric disorders, socioeconomic status and calendar period.
Their findings that sex differences in psychiatric disorders exist almost across the whole life supports the need of gendered mental health prevention strategies. The variation in these differences by age and socioeconomic status suggests that the current knowledge can be enhanced by integrating data on age and socioeconomic status. This study also provides evidence for screening and intervention strategies that focus on specific age groups and socially disadvantaged populations, where pronounced sex disparity in psychiatric disorders were observed.
A new study reveals widespread resistance of a major bacterial pathogen to the active ingredients in cleaning agents commonly used in hospitals and homes. The American Chemical Society Infectious Diseases published the research led by chemists at Emory University. It demonstrates the surprising level of resistance to cleaning agents of multidrug-resistant Pseudomonas aeruginosa, a pathogen of particular concern in hospital settings.
The study also identifies biocides that are highly effective against P. aeruginosa, including a novel compound developed at Emory in collaboration with Villanova University. The researchers describe how these biocides work differently than most disinfectants currently in use.
“We hope our findings can help guide hospitals to reconsider protocols for the sanitation of patient rooms and other facilities,” says William Wuest, Emory professor of chemistry and a senior author of the study. “We also hope that our findings of a new mechanism of action against these bacterial strains may help in the design of future disinfectant products.”
First authors of the study are Christian Sanchez (who did the work as an Emory PhD student in chemistry and, following graduation, joined the faculty at Samford University) and German Vargas-Cuebas, an Emory PhD candidate in microbiology through Laney Graduate School.
“Resistance of pathogens to cleaning agents is an area that’s often overlooked,” Vargas-Cuebas says, “but it’s an important area of study, especially with the rise in antibiotic-resistant pathogens worldwide.”
Kevin Minbiole, professor of chemistry at Villanova, is co-senior author of the paper.
Workhorse disinfectants losing steam
Quaternary ammonium compounds, or QACs, are active ingredients commonly seen in household and hospital cleaners, including some disinfectant sprays and liquids, antibacterial sanitizing wipes and soaps.
“There are a handful of QACs that have been the workhorse disinfectants for around 100 years, on the frontline of most homes and hospitals,” Wuest says. “Very little has been done to modify their structures because they have long worked so well against many common bacteria, viruses, molds and fungi and they’re so simple and cheap to make.”
The Wuest lab is a leader in studies of QACs and other disinfecting agents. One issue Wuest and his colleagues have identified is that some bacterial strains are developing resistance to QACs. That trend could cause serious problems for sanitation in hospitals.
A pathogen of critical priority
More than 2.8 million antimicrobial-resistant infections occur in the United States each year, leading to more than 35,000 deaths, according to the Centers for Disease Control and Prevention (CDC).
The CDC names multidrug-resistant P. aeruginosa as one of seven pathogens causing infections that increased in the United States during the COVID-19 pandemic and remain above prepandemic levels.
Worldwide, P. aeruginosa causes more than 500,000 deaths annually and has been named a pathogen of critical priority by the World Health Organization.
P. aeruginosa is commonly found in the environment, including in soil and freshwater. Reservoirs in hospital settings can include drains, taps, sinks and equipment washers.
While the bacterium generally does not affect healthy people it can cause infections in individuals with cystic fibrosis and those who are immunocompromised, such as patients with burns, cancer and many other serious conditions. Patients with invasive devices such as catheters are also at risk due to the ability of P. aeruginosa to form biofilms on the surfaces of these devices.
P. aeruginosa, like other gram-negative bacteria, is enclosed in a second, fatty outer membrane that acts as a protective capsule, making it more difficult to kill.
How QACs kill
QACs have a nitrogen atom at the center of four carbon chains. In simplest terms, the positively charged head of the nitrogen center is drawn to the negatively charged phosphates of the fatty acids encasing P. aeruginosa and many other bacteria and viruses. The heads of the carbon chains act like spearpoints, stabbing into both protective fatty membranes and inner cellular membranes and causing pathogens to disintegrate.
The researchers tested 20 different drug-resistant strains of P. aeruginosa collected from hospitals around the world by the Walter Reed National Military Medical Center as part of the Multidrug-Resistant Organism Repository and Surveillance Network.
The results showed that all 20 strains were at least partially resistant to QACs — the common active ingredient in most front-line cleaning agents — and 80% of the strains were fully resistant to QACs.
“This mechanism has worked for 100 years essentially by slicing into the outer and inner membranes of a pathogen and destroying them,” Wuest says. “We were surprised to see the level at which that appears to no longer be the case.”
Improper use of cleaning agents may be one factor leading to resistance, Wuest theorizes.
“QACs don’t immediately kill,” he explains. “After application, it’s important to wait four or five minutes before wiping these cleaning agents away. It’s also important to use the right concentration. If used inappropriately, some bacteria can survive, which can lead to them developing resistance.”
Greater use of cleaning agents during the COVID-19 pandemic may have given P. aeruginosa and some other hard-to-kill pathogens more opportunities to develop resistance, he adds.
A new method that ‘works surprisingly well’
For the current paper, the researchers also tested the resistance of the panel of multidrug-resistant P. aeruginosa strains against a new quaternary phosphonium compound, or QPC, developed in the Wuest and Minbiole labs. The results showed that the compound was highly effective at killing all 20 of the resistant P. aeruginosa strains.
“It works surprisingly well even at a low concentration,” Vargas-Cuebas says.
The researchers demonstrated that their novel QPC works not by piercing the protective outer capsule of a P. aeruginosa bacterium but by diffusing through this outer membrane and then selectively attacking the inner cellular membrane.
“It’s counterintuitive,” Wuest remarks. “You would think that the approach of conventional biocides, to take out both membranes, would be a more effective way to kill P. aeruginosa. Why does passively diffusing through the outer membrane and focusing on attacking the inner membrane make our QPC compound more effective? We don’t know yet. It’s like a magic trick.”
They showed that this same mechanism underlies the effectiveness of two commercial antiseptics: octenidine, more commonly used in Europe as a hospital antiseptic, and chlorhexidine, a common ingredient in mouthwashes.
Wuest and colleagues plan to continue research into how this newly identified mechanism may work against an array of pathogens and how that might translate into new biocides and more effective cleaning protocols in hospitals and other settings.
“Our work is paving the way for much-needed innovations in disinfectant research,” Wuest says.
Merck Foundation, the philanthropic arm of Merck KGaA Germany has been awarded as the “NGO of the Year 2024”, the Most Influential NGO Shaping Africa’s Future and Leading Community Empowerment, by Avance Media, a leading rating and voting firm in Africa.
On receiving the accolade, Senator, Dr. Rasha Kelej, CEO of Merck Foundation and One of 100 Most Influential Africans for five consecutive years – from 2019 till 2023 expressed, “I am thrilled and proud to share that Merck Foundation has been voted as the “NGO OF THE YEAR 2024”, out of the list of 10 NGOs Leading Community Empowerment in Africa, shortlisted by Avance Media, big thanks for everyone who voted for us, we would not have been able to make it without your support and trust in Merck Foundation’s significant role in shaping the future of African communities.”
Winning the “NGO of the Year 2024 ” as per people’s votes acknowledged their collective efforts in shaping Africa’s future through key sectors such as health, education, and economic empowerment.
“This recognition inspires me and my team to continue our mission to transform the patient care landscape, drive cultural change, support girls’ education, empower women, and break the stigma around infertility in Africa and beyond. We are committed to contributing to improving lives of the people.” Dr. Rasha Kelej added.
Merck Foundation was initially announced as one of 10 Most Influential NGOs Shaping Africa’s Future, along with other leading NGOs working in Africa like Save the Children, Plan International, Doctors without Borders, Africa Women’s Development Fun, African Medical & Research Foundation, and others. Merck Foundation was then voted for as the NGO of the Year 2024, out of the 10 NGOs listed.
Since 2012, Merck Foundation, together with their Ambassadors, the First Ladies of Africa, and Partners like Ministries of Health, Gender, Education, and Communication, continues to transform patient care across Africa and bring cultural shift with regards to a wide range of social and health issues, including breaking the stigma around infertility, supporting girls’ education, ending child marriage and FGM, stopping gender-based violence, and raising awareness about diabetes and hypertension.
“I am happy to share that we have provided more than 2080 scholarships to young doctors from 52 countries, in 44 underserved medical specialties. Many of our Merck Foundation Alumni are becoming the first specialists in their countries. Together, we continue to make history,” Dr. Kelej added.
The scholarships of one year, two year and three year fellowship, diploma and master course have been provided in 44 underserved medical specialties like Oncology, Diabetes, Cardiology, Endocrinology, Respiratory, Acute Medicine, Sexual and Reproductive medicine, Embryology, Respiratory, Critical care, Psychiatry, General Surgery, Dermatology, Emergency and Resuscitation Medicine, Gastroenterology, Neuroimaging for Research, Pain Management, Neonatal Medicine, Clinical Microbiology & Infectious Diseases, Advanced Surgical Practice and more.
Through their “More Than a Mother” campaign which is a strong movement that aims to empower infertile and childless women through access to information, education and change of mindset, Merck Foundation has been building quality and equitable reproductive and fertility care capacity, breaking infertility stigma and raising awareness about Infertility Prevention and Male Infertility.
“I am happy that we are contributing to building and advancing fertility care capacity in Africa and improving better access to women’s health. I am very proud to share that we have provided till today more than 650 scholarships of Embryology, Fertility and Reproductive care to young doctors from 39 different countries. Moreover, we also support childless women by helping them start their own small businesses. It is all about giving every woman the respect and support she deserves to lead a fulfilling life, with or without a child”, Senator, Rasha Kelej explained.
Moreover, Merck Foundation strongly believe that Education is one of the most critical areas of women empowerment. Therefore, through their “Educating Linda”, Merck Foundation contributes to the future of young African girls who are brilliant but underprivileged, by providing more than 700 scholarships, to cover their school fees till they graduate, and thousands of school items to schoolgirls in many African countries including Botswana, Burundi, Malawi, Ghana, The Gambia, Nigeria, Zambia, Zimbabwe, Ghana, Namibia, Democratic Republic of the Congo, Niger and more.
I am happy that we are contributing to building and advancing fertility care capacity in Africa and improving better access to women’s health
Dr. Rasha Kelej
Additionally, Merck Foundation has been raising awareness about many critical social issues including breaking infertility stigma, supporting girl education, women empowerment, ending FGM & child marriage, stopping GBV and important health issues like Diabetes & Hypertension prevention, early detection & Management; promoting healthy lifestyle; infertility awareness & management and more. Merck Foundation has introduced many unique and innovative ways like Songs, Animation Films, Children Storybooks, Health Media Trainings, “Our Africa” TV Program, Awards for Media, Filmmakers, Fashion Designers and Musicians and more.
