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Opioids like morphine are widely used in medical practice due to their powerful pain-relieving effects. However, they carry the risk of serious adverse effects such as respiratory depression and drug dependence. For this reason, Japan has strict regulations in place to ensure that these medications are prescribed only by authorized physicians.
In the United States, however, the opioid OxyContin was once prescribed frequently triggering a surge in the misuse of synthetic opioids such as fentanyl. As a result, the number of deaths caused by opioid overdose surpassed 80,000 in 2023, escalating into a national public health crisis now referred to as the “opioid crisis.”
Opioids may soon have a rival, however. A team of researchers at Kyoto University has recently discovered a novel analgesic, or pain reliever, which exerts its effect through an entirely different mechanism. Clinical development of their drug ADRIANA is currently underway as part of an international collaborative effort.
“If successfully commercialized, ADRIANA would offer a new pain management option that does not rely on opioids, contributing significantly to the reduction of opioid use in clinical settings,” says corresponding author Masatoshi Hagiwara, a specially-appointed professor at Kyoto University.
The research team was first inspired by substances that mimic noradrenaline, which is released in life-threatening situations andactivates α2A-adrenoceptors to suppress pain. However, these pose a high risk of cardiovascular instability. After observing noradrenaline levels and α2B-adrenoceptors, the team hypothesized that selectively blocking α2B-adrenoceptors could elevate noradrenaline levels, leading to activation of α2A-adrenoceptors and resulting in pain relief without causing cardiovascular instability.
To identify selective inhibitors of α2B-adrenoceptors and measure the activity of individual α2-adrenoceptor subtypes, the researchers employed a novel technology known as the TGFα shedding assay and conducted compound screening leading to their discovery of the world’s first selective α2B-adrenoceptor antagonist.
After success in administering the compound to mice and conducting non-clinical studies to assess its safety, physician-led clinical trials were conducted at Kyoto University Hospital. Both the Phase I trial in healthy volunteers and the Phase II trial in patients with postoperative pain following lung cancer surgery yielded highly promising results.
Building on these outcomes, preparations are now underway for a large-scale Phase II clinical trial in the United States, in collaboration with BTB Therapeutics, Inc, a Kyoto University-originated venture company.
As Japan’s first non-opioid analgesic, ADRIANA has the potential not only to relieve severe pain for patients worldwide but could also play a meaningful role in addressing the opioid crisis — a pressing social issue in the United States — and thus contribute to international public health efforts.
“We aim to evaluate the analgesic effects of ADRIANA across various types of pain and ultimately make this treatment accessible to a broader population of patients suffering from chronic pain,” says Hagiwara.

A systematic review analyzed associations of high-concentration delta-9-tetrahydrocannabinol (THC) cannabis products with mental health outcomes. The review found that high-concentration THC products are associated with unfavorable mental health outcomes, particularly for psychosis or schizophrenia and cannabis use disorder (CUD). However, there are limitations to currently available evidence and the researchers call for studies with improved designs to provide more accurate guidance for clinicians and the public. The review is published in Annals of Internal Medicine.
Researchers from University of Colorado Anschutz Medical Campus and colleagues analyzed 99 studies comprising 221,097 participants completed between 1977 and 2023. Study selection was intentionally broad and included studies examining associations between high-concentration cannabis products and mental health outcomes regardless of whether the study had the purpose of evaluating therapeutic effects.
High-concentration cannabis products were defined as having THC concentration exceeding 5 mg THC or 10% THC per serving or products described as “high-potency concentrate,” “shatter,” or “dab.” The mental health outcomes of interest included anxiety, depression, psychosis, schizophrenia, CUD and other substance use disorders. The researchers defined acute effects (within 12 hours), post-acute effects (after consistent use for 1 to 2 months), and long-term effects (after consistent use for > 1 year).
In studies not testing for therapeutic effects, high concentration THC products were associated with psychosis, schizophrenia, and cannabis use disorder. No therapeutic studies found favorable effects on psychosis or schizophrenia. Of non-therapeutic studies, 53% identified unfavorable associations with anxiety and 41% found unfavorable associations with depression. Among therapeutic studies, some suggested beneficial effects for anxiety (47%) and depression (48%), while others suggested unfavorable effects (24% for anxiety and 30% for depression).
The findings reinforce previous conclusions that higher THC concentrations increase the risk for adverse mental health outcomes; however, they fall short of providing the definitive evidence needed to provide clear advice to patients.

Weight loss drugs like Ozempic and Wegovy are used by over 15 million adults in the U.S., or 4.5% of the population. Despite their effectiveness, they have drawbacks. Their effect may not last after discontinuing use, and side effects including osteoporosis and muscle loss have raised concerns about long-term harms. They also induce nausea, which can make it difficult to stay the course of treatment.
Now Tufts researchers led by Krishna Kumar, Robinson Professor of Chemistry, have designed a new, next-generation compound with hopes that it could be more effective with fewer side effects, which they report in a paper in the Journal of the American Chemical Society.
While weight loss drugs currently on the market and in development target one, two, or even three hormone receptors related to glucose metabolism and the desire to eat, the Tufts team has identified a fourth target that could potentially further enhance the control strategy.
“Obesity is linked to over 180 different disease conditions, including cancer, cardiovascular disease, osteoarthritis, liver disease, and type 2 diabetes, and affects over 650 million people worldwide,” said Kumar. “What drives us is the idea that we can design a single drug to treat obesity and simultaneously mitigate the risk of developing a long list of health problems plaguing society.”
How the Drugs Work
After we eat a meal, our gut and brain trigger a hormonal “fuel gauge” that regulates levels of glucose and tells us when we have had enough to eat.
The hormone glucagon-like peptide 1 (GLP-1) is released to help stimulate the production of insulin and the uptake of glucose in muscle and other tissues. With the cells now loaded with fuel, the level of glucose in the blood returns to normal. Ozempic uses GLP-1 with slight modifications to increase its availability in the bloodstream. Its success in controlling blood glucose has prompted the American Diabetes Association to recommend it and other GLP-1-based drugs as the new first line injectable treatments for diabetes, ahead of insulin.

But GLP-1 also acts directly on the brain, making us feel full after having a meal, and it slows down the rate that the stomach contents are emptied into the intestines, creating a more evenly paced release of nutrients and glucose into the bloodstream. That’s why it has also become extremely popular as a weight loss treatment.
It’s still not a perfect drug strategy for weight loss, though. “The biggest problem with GLP-1 drugs is that they have to be injected once a week, and they can induce a very strong feeling of nausea,” said Kumar. “As much as 40% of people using these drugs give up after the first month.”
A second hormone released after eating is glucose-dependent insulinotropic peptide (GIP). It also makes us feel full after a meal. GIP looks a lot like GLP-1, so rather than administer two drugs, researchers created one peptide that incorporates structural elements of both — what’s called in drug development a chimera. That drug, called Mounjaro or Zepbound (the brand names for tirzepatide), has the added benefit of significantly reducing nausea. As a more tolerable treatment, it may overtake Ozempic in the weight loss market.
“And then there is a third hormone, glucagon,” said Kumar. “Paradoxically, it actually increases blood glucose, but at the same time increases the expenditure of energy in cells of the body, raises body temperature, and suppresses appetite.” By adding glucagon to the mix, GLP-1 and GIP end up neutralizing its glucose-enhancing effect, leaving the remaining functionalities of all three hormones working together to enhance weight loss.
Glucagon is also similar in structure to GLP-1 and GIP, so drug developers created a single chimera peptide that incorporates elements of all three hormones, which can be recognized by their three separate receptors. That drug, called retatrudide, is currently in clinical trials that indicate even greater achievable weight loss (up to 24%) compared to the original GLP-1 drugs (6-15%).
Going for the Weight Loss Gold Standard with a Fourth Target
“The goal that people are trying to shoot for is bariatric surgery,” said Kumar. That’s a surgical procedure significantly reducing the size of the stomach, which can achieve long-lasting weight loss up to 30%. “For individuals with persistent obesity and potential deadly associated conditions, it becomes a necessary but invasive treatment.”

Current injectable weight loss drugs still fall short of that gold standard, so the Tufts chemists are focused on a drug redesign that could match the 30% weight loss outcome.
“There is one more hormone we wanted to bring in to complete a weight control quartet,” said Tristan Dinsmore, a graduate student in the Kumar lab and the lead author of the study. “It’s called peptide YY (PYY). This molecule is also secreted by the gut after we eat a meal, and its job is to reduce appetite and slow the process of emptying food from the stomach, but via different mechanisms than either GLP-1 or GIP. It may also be involved in directly ‘burning off’ fat.”
PYY is from a separate and structurally unrelated class of hormones than the first three, so blending its structure into a chimeric peptide that also mimics GLP-1, GIP, and glucagon was not easy. Instead, the Tufts team was able to join two peptide segments end-to-end, creating a new ‘tetra-functional’ clinical candidate.
“One of the limitations of the current drugs is that individual variation, possibly including how people express target receptors or respond to their corresponding hormones, can lead to lesser than desired weight loss outcomes in many patients,” said Martin Beinborn, visiting scholar in the Department of Chemistry. “By hitting four different hormone receptors at the same time, we hope to improve the chances of averaging out such variation toward the goal of achieving greater and more consistent overall effectiveness.”
“A second issue is that patients tend to regain weight after discontinuing currently available GLP-1 related drugs,” said Beinborn, who notes that lifestyle changes should ideally be a complement to medication treatment. This two-pronged approach will not only support reaching and keeping one’s target weight, but may also help preserve bone and muscle mass.
“Recent studies indicate that weight rebound after drug discontinuation is delayed with the newer, more effective GLP-1 mimetics,” he said. “Extending from this observation, one may speculate that multi-chimeras along the lines of the one we discovered could get us closer to the bariatric surgery standard of lasting weight loss.”

A fading sense of smell can be one of the earliest signs of Alzheimer’s disease even before cognitive impairments manifest. Research by scientists at DZNE and Ludwig-Maximilians-Universität München (LMU) sheds new light on this phenomenon, pointing to a significant role for the brain’s immune response, which seems to fatally attack neuronal fibers crucial for the perception of odors. The study, published in the journal Nature Communications, is based on observations in mice and humans, including analysis of brain tissue and so-called PET scanning. These findings may help to devise ways for early diagnosis and, consequently, early treatment.
The researchers come to the conclusion that these olfactory dysfunctions arise because immune cells of the brain called “microglia” remove connections between two brain regions, namely the olfactory bulb and the locus coeruleus. The olfactory bulb, located in the forebrain, analyzes sensory information from the nose’s scent receptors. The locus coeruleus, a region of the brainstem, influences this processing by means of long nerve fibers originating from neurons in the locus coeruleus and extending all the way to the olfactory bulb. “The locus coeruleus regulates a variety physiological mechanisms. These include, for example, cerebral blood flow, sleep-wake cycles, and sensory processing. The latter applies, in particular, also to the sense of smell,” says Dr. Lars Paeger, a scientist at DZNE and LMU. “Our study suggests that in early Alzheimer’s disease, changes occur in the nerve fibers linking the locus coeruleus to the olfactory bulb. These alterations signal to the microglia that affected fibers are defective or superfluous. Consequently, the microglia break them down.”
Alterations in the membrane
Specifically, the team of Dr. Lars Paeger and Prof. Dr. Jochen Herms, who is a co-author of the current publication, found evidence of changes in the composition of the membranes of the affected nerve fibers: Phosphatidylserine, a fatty acid that usually occurs inside a neuron’s membrane, had been moved to the outside. “Presence of phosphatidylserine at the outer site of the cell membrane is known to be an “eat-me” signal for microglia. In the olfactory bulb, this is usually associated with a process called synaptic pruning, which serves to remove unnecessary or dysfunctional neuronal connections,” explains Paeger. “In our situation, we assume that the shift in membrane composition is triggered by hyperactivity of the affected neurons due to Alzheimer’s disease. That is, these neurons exhibit abnormal firing.”
A wide range of data
The findings of Paeger and colleagues are based on a plethora of observations. These include studies on mice with features of Alzheimer’s disease, analysis of brain samples from deceased Alzheimer’s patients, and positron emission tomography (PET) scans of the brains of individuals with Alzheimer’s or mild cognitive impairment. “Smell issues in Alzheimer’s disease and damage to the associated nerves have been discussed for some time. However, the causes were unclear until yet. Now, our findings point to an immunological mechanism as cause for such dysfunctions – and, in particular, that such events already arise in the early stages of Alzheimer’s disease,” says Joachim Herms, a research group leader at DZNE and LMU as well as a member of the Munich-based “SyNergy” Cluster of Excellence.
Perspectives for early diagnosis
So-called amyloid-beta antibodies have recently become available for the treatment of Alzheimer’s. For this novel therapy to be effective, it needs to be applied at an early stage of the disease, and this is precisely where the current research could be significant. “Our findings could pave the way for the early identification of patients at risk of developing Alzheimer’s, enabling them to undergo comprehensive testing to confirm the diagnosis before cognitive problems arise. This would allow earlier intervention with amyloid-beta antibodies, increasing the probability of a positive response,” says Herms.

One shot of an RSV vaccine protects adults ages 60 or older from RSV-associated hospitalization and critical illness during two consecutive RSV seasons, according to a study published in JAMA on August 30 by the IVY Network research group.
RSV causes substantial seasonal illness during fall and winter in the U.S., with an estimated 100,000-150,000 hospitalizations and 4,000-8,000 deaths occurring annually among adults 60 or older.
The results reinforce the recommendations for RSV vaccines in older adults and lay the groundwork for understanding how long a single dose of the vaccine may be effective, according to Wesley Self, MD, MPH, principal investigator for the IVY Network and Senior Vice President for Clinical Research at Vanderbilt University Medical Center.
“These results clearly demonstrate that the RSV vaccines prevent hospitalizations and critical illness due to RSV infection among older Americans,” Self said. “It is exciting to see the public health benefits of this new vaccination program.”
Investigators used data from a multicenter hospital network known as the IVY Network (The Investigating Respiratory Viruses in the Acutely Ill Network) to assess RSV vaccine effectiveness. They used a test-negative, case-control study design among 6,958 persons 60 years or older who had been hospitalized with acute respiratory illness at one of 26 hospitals in 20 US states during two RSV seasons from October 1, 2023-March 31, 2024 and October 1, 2024-April 30, 2025.
Overall, vaccination reduced the risk of RSV hospitalization by 58% during two RSV seasons, including 69% in the first year after vaccination and 48% in the second year after vaccination.
“Our data show that the beneficial effects of RSV vaccines appear to wane over time,” Self said. “Redosing the vaccine at some interval after the initial dose could be a strategy to maintain protection over longer periods of time. It will be important to continue to closely monitor vaccine effectiveness over time to understand how long the benefit lasts after a single dose and if repeat dosing should be considered.”
Current RSV vaccine recommendations are for all adults aged 75 years and older and those aged 60-74 years who are at an increased risk of severe RSV.
This study was funded by the U.S. Centers for Disease Control and Prevention (CDC) via award 75D30122C14944.

A new treatment has been shown to significantly lower blood pressure in people whose levels stay dangerously high, despite taking several existing medicines, according to the results of a Phase III clinical trial led by a UCL Professor.
Globally around 1.3 billion people have high blood pressure (hypertension), and in around half of cases the condition is uncontrolled or treatment resistant. These individuals face a much greater risk of heart attack, stroke, kidney disease, and early death. In the UK the number of people with hypertension is around 14 million.
The international BaxHTN trial, led by Professor Bryan Williams (UCL Institute of Cardiovascular Science) and sponsored by AstraZeneca, assessed the new drug baxdrostat – which is taken as a tablet – with participation from nearly 800 patients across 214 clinics worldwide.
The study was supported by the NIHR Biomedical Research Centre at UCLH.
Results were presented on August 30th at the European Society of Cardiology (ESC) Congress 2025 in Madrid and are being simultaneously published in the New England Journal of Medicine.
The trial results showed that, after 12 weeks, patients taking baxdrostat (1 mg or 2 mg once daily in pill form) saw their blood pressure fall by around 9-10 mmHg more than placebo – a reduction large enough to cut cardiovascular risk. About 4 in 10 patients reached healthy blood pressure levels, compared with fewer than 2 in 10 on placebo.
Principal Investigator, Professor Williams, who is presenting the results at ESC, said: “Achieving a nearly 10 mmHg reduction in systolic blood pressure with baxdrostat in the BaxHTN Phase III trial is exciting, as this level of reduction is linked to substantially lower risk of heart attack, stroke, heart failure and kidney disease.”
How baxdrostat works

Blood pressure is strongly influenced by a hormone called aldosterone, which helps the kidneys regulate salt and water balance.
Some people produce too much aldosterone, causing the body to hold onto salt and water. This aldosterone dysregulation pushes blood pressure up and makes it very difficult to control.
Addressing aldosterone dysregulation has been a key effort in research over many decades, but it has been so far difficult to achieve.
Baxdrostat works by blocking aldosterone production, directly addressing this driver of high blood pressure (hypertension).
Professor Williams, Chair of Medicine at UCL, said: “These findings are an important advance in treatment and in our understanding of the cause of difficult to control blood pressure.
“Around half of people treated for hypertension do not have it controlled, however this is a conservative estimate and the number is likely higher, especially as the target blood pressure we try to reach is now much lower than it was previously.*
“In patients with uncontrolled or resistant hypertension, the addition of baxdrostat 1mg or 2mg once daily to background antihypertensive therapy led to clinically meaningful reductions in systolic blood pressure, which persisted up to 32 weeks with no unanticipated safety findings.

“This suggests that aldosterone is playing an important role in causing difficult to control blood pressure in millions of patients and offers hope for more effective treatment in the future.”
Historically higher income Western countries were reported to have far higher levels of hypertension; however, largely due to changing diets (adding less salt to food), the numbers of people living with the condition is now far higher in Eastern and lower income countries. More than half of those affected live in Asia, including 226 million people in China and 199 million in India**.
Professor Williams added: “The results suggest that this drug could potentially help up to half a billion people globally – and as many as 10 million people in the UK alone, especially at the new target level for optimal blood pressure control.”
*The ESC 2024 hypertension guidelines recommended a target blood pressure of less than 130/80 mmHg. Prior to 2024 the target had been 140/90 mmHg.
** Figures from Blood Pressure UK

Beta blockers—drugs commonly prescribed for a range of cardiac conditions, including heart attacks—provide no clinical benefit for patients who have had an uncomplicated myocardial infarction with preserved heart function. Beta blockers have been the standard treatment for these patients for 40 years.
This is a breakthrough discovery from the “REBOOT Trial” with senior investigator Valentin Fuster, MD, PhD, President of Mount Sinai Fuster Heart Hospital and General Director of Spain’s Centro Nacional de Investigaciones Cardiovasculares (CNIC). The study results, which could overturn a standard treatment paradigm, were presented on Saturday, August 30, during a “Hot Line” session at the European Society of Cardiology Congress in Madrid, and simultaneously published in The New England Journal of Medicine.Additionally, a REBOOT substudy, published on August 30 in the European Heart Journal, shows that women treated with beta blockers had a higher risk of death, heart attack, or hospitalization for heart failure compared to women not receiving the drug. Men did not have this increased risk.
“This trial will reshape all international clinical guidelines. It joins other previous landmark trials led by CNIC and Mount Sinai—such as SECURE with the polypill and DapaTAVI, with SLT2 inhibition associated to TAVI—that have already transformed some global approaches to cardiovascular disease,” says Dr. Fuster.
The SECURE trial showed a polypill, a single pill that that combines three medications – which contains aspirin, ramipril, and atorvastatin – reduces cardiovascular events by 33 percent in patients treated with this after a heart attack. The DapaTAVI trial showed both dapagliflozin and the related medication empagliflozin – drugs used to treat diabetes- improves the prognosis of patients with aortic stenosis treated by transcatheter aortic valve implantation.
“REBOOT will change clinical practice worldwide,” says Principal Investigator Borja Ibáñez, MD, CNIC’s Scientific Director, who presented the results. “Currently, more than 80 percent of patients with uncomplicated myocardial infarction are discharged on beta blockers. The REBOOT findings represent one of the most significant advances in heart attack treatment in decades.”
Although generally considered safe, beta blockers can cause side effects such as fatigue, bradycardia (low heart rate), and sexual dysfunction. For more than 40 years, beta blockers have been prescribed as a standard treatment after a heart attack, but their benefit in the context of modern treatments was unproven. The REBOOT trial, is the largest clinical trial on this subject. The international study was coordinated by CNIC in collaboration with the Mario Negri Institute for Pharmacological Research in Milan.
Researchers enrolled 8,505 patients across 109 hospitals in Spain and Italy. Participants were randomly assigned to receive or not receive beta blockers after hospital discharge. All patients otherwise received the current standard of care and were followed for a median of nearly four years. The results showed no significant differences between the two groups in rates of death, recurrent heart attack, or hospitalization for heart failure.

A REBOOT subgroup analysis found that women treated with beta blockers experienced more adverse events. Results show women treated with beta-blockers had a 2.7 percent higher absolute risk of mortality compared to those not treated with beta-blockers during the 3.7 years of follow-up of the study. The elevated risk when treated with beta-blockers was restricted to women with a complete normal cardiac function after a heart attack (left ventricular ejection fraction of 50 percent or higher). Those with a mild deterioration in cardiac function did not have an excess risk of adverse outcomes when treated with beta-blockers.
“After a heart attack, patients are typically prescribed multiple medications, which can make adherence difficult,” explains Dr. Ibáñez. “Beta blockers were added to standard treatment early on because they significantly reduced mortality at the time. Their benefits were linked to reduced cardiac oxygen demand and arrhythmia prevention. But therapies have evolved. Today, occluded coronary arteries are reopened rapidly and systematically, drastically lowering the risk of serious complications such as arrhythmias. In this new context—where the extent of heart damage is smaller—the need for beta blockers is unclear. While we often test new drugs, it’s much less common to rigorously question the continued need for older treatments.”
That was the motivation behind REBOOT.
“The trial was designed to optimize heart attack care based on solid scientific evidence and without commercial interests. These results will help streamline treatment, reduce side effects, and improve quality of life for thousands of patients every year,” Dr. Ibanez adds.
REBOOT was conducted without pharmaceutical industry funding.

3 hours agoShareSaveMaia DaviesBBC NewsShareSaveGetty ImagesA baby whose mother was not vaccinated against whooping cough while pregnant has died after contracting the infection, the UK Health Security Agency (UKHSA) has said.The death, which occurred between January and June 2025, is the first fatal case of whooping cough in the UK this year.It follows government warnings about low vaccine uptake, including among children, as well as an increase in vaccine hesitancy. None of the main childhood vaccines in England reached the uptake target of 95% last year, recent data from the health agency showed.Whooping cough is a bacterial infection of the lungs and airways which can be fatal, particularly for babies. Eleven infants died of the illness in 2024.Pregnant women, as well as infants and young children, are advised to get vaccinated against it. The uptake among pregnant women currently stands at 72.6%.The UKHSA says vaccination during pregnancy, introduced in late 2012, is “key to passively protecting babies” in their first weeks of life. Infants are first offered a jab which protects against whooping cough at eight weeks old.Thirty-three infants have died of the illness since 2013 – 27 of whom had mothers who had not received the jab in pregnancy.The UKHSA’s deputy director Dr Gayatri Amirthalingam said the case was a reminder of “how severe whooping cough can be for very young babies”.She continued: “Vaccination is the best defence against whooping cough and it is vital that pregnant women and young infants receive their vaccines at the right time, ideally between 20 and 32 weeks.”The health agency and ministers have recently warned of declining vaccine uptake among children.Last year, the share of five-year-olds who had received one dose of the MMR (measles, mumps and rubella) vaccine remained at its lowest level since 2010/11, at 91.9%. The uptake rate for both doses – 83.7% – was at its lowest since 2009/10.The World Health Organization (WHO) recommends at least 95% of children should receive vaccine doses to achieve herd immunity.Poor uptake of the MMR vaccine was blamed for a rise in measles cases earlier this year. In July, a child died at Alder Hey Children’s Hospital after contracting the illness.The government this week said all young children in the UK would be offered a free chickenpox vaccine by the NHS from January 2026.Health minister Stephen Kinnock told the BBC that the government was concerned about vaccine uptake and hesitancy, which he said had increased after the Covid-19 pandemic.He said campaigns explaining “the benefits of getting vaccinated and the fact that this is 100% safe” would be brought forward as the government sought to “win this battle against the conspiracy theorists”.

A new research perspective was recently published in Aging, titled “Exercise as a geroprotector: focusing on epigenetic aging.”
In this perspective, led by Takuji Kawamura from Tohoku University, researchers reviewed existing evidence from scientific studies showing that regular exercise, physical activity, and fitness may influence epigenetic aging and potentially reverse it, offering a promising way to extend healthspan and improve long-term health.
Epigenetic aging refers to changes in the body’s DNA that reflect how quickly a person is aging at the molecular level. It is measured using epigenetic clocks, which analyze patterns of DNA methylation, a chemical modification that can affect gene activity. Unlike chronological age, which simply counts the number of years lived, epigenetic aging presents a more accurate picture of how well the body’s cells and tissues are functioning. This process is influenced by various factors, including lifestyle, and has become a powerful tool for studying aging.
This perspective highlights that while general physical activity, such as walking or doing household tasks, offers health benefits, structured exercise routines that are planned, repetitive, and goal-directed appear to have stronger effects on slowing epigenetic aging. Physical fitness, especially high cardiorespiratory capacity, is also closely associated with slower epigenetic aging.
The authors also discuss key findings from both human and animal studies. In mice, structured endurance and resistance training reduced age-related molecular changes in muscle tissue. In humans, multi-week exercise interventions demonstrated reductions in biological age markers in blood and skeletal muscle. One study found that sedentary middle-aged women reduced their epigenetic age by two years after just eight weeks of combined aerobic and strength training. Another study showed that older men with higher oxygen uptake levels, a key measure of cardiovascular fitness, had significantly slower epigenetic aging.
“These findings suggest that maintaining physical fitness delays epigenetic aging in multiple organs and supports the notion that exercise as a geroprotector confers benefits to various organs.”
The research also examines which organs benefit most from exercise. While skeletal muscle has been a central focus, new evidence shows that regular physical training may also slow aging in the heart, liver, fat tissue, and even the gut. In addition, Olympic athletes were found to have slower epigenetic aging than non-athletes, suggesting that long-term, intensive physical activity may have lasting anti-aging effects.
The authors call for further research to understand why some individuals respond more strongly to exercise than others and how different types of training influence aging in various organs. They also point out the importance of developing personalized exercise programs to maximize anti-aging benefits. Overall, the findings support the growing recognition that maintaining physical fitness is not only essential for daily health but may also serve as one of the most effective tools for slowing the body’s internal aging process.

The blood pressure lowering effect of nitrate-rich beetroot juice in older people may be due to specific changes in their oral microbiome, according to the largest study of its kind.
Researchers at the University of Exeter conducted the study, published in the journal Free Radical Biology and Medicine, comparing responses between a group of older adults to that of younger adults. Previous research has shown that a high nitrate diet can reduce blood pressure, which can help reduce risk of heart disease.
Nitrate is crucial to the body and is consumed as a natural part of a vegetable-rich diet.  When the older adults drank a concentrated beetroot juice ‘shot’ twice a day for two weeks*, their blood pressure decreased – an effect not seen in the younger group.
The new study, funded by a BBSRC Industrial Partnership Award, provides evidence that this outcome was likely caused by the suppression of potentially harmful bacteria in the mouth.  An imbalance between beneficial and harmful oral bacteria can decrease the conversion of nitrate (abundant in vegetable-rich diets) to nitric oxide. Nitric oxide is key to healthy functioning of the blood vessels, and therefore the regulation of blood pressure.
Study author Professor Anni Vanhatalo, of the University of Exeter, said: “We know that a nitrate-rich diet has health benefits, and older people produce less of their own nitric oxide as they age. They also tend to have higher blood pressure, which can be linked to cardiovascular complications like heart attack and stroke. Encouraging older adults to consume more nitrate-rich vegetables could have significant long term health benefits. The good news is that if you don’t like beetroot, there are many nitrate-rich alternatives like spinach, rocket, fennel, celery and kale.”
The study recruited 39 adults aged under 30, and 36 adults in their 60s and 70s through the NIHR Exeter Clinical Research Facility. The trial was supported by the Exeter Clinical Trials Unit. Each group spent two weeks taking regular doses of nitrate-rich beetroot juice and two weeks on a placebo version of the juice with nitrate stripped out. Each condition had a two week “wash out” period in between to reset. The team then used a bacterial gene sequencing method to analyse which bacteria were present in the mouth before and after each condition.
In both groups, the make-up of the oral microbiome changed significantly after drinking the nitrate-rich beetroot juice, but these changes differed between the younger and older age groups.

The older age group experienced a notable decrease in the mouth bacteria Prevotella after drinking the nitrate rich juice, and an increase in the growth of bacteria known to benefit health such as Neisseria. The older group had higher average blood pressure at the start of the study, which fell after taking the nitrate-rich beetroot juice, but not after taking the placebo supplement.
Co-author Professor Andy Jones, of the University of Exeter, said: “This study shows that nitrate-rich foods alter the oral microbiome in a way that could result in less  inflammation, as well as a lowering of blood pressure in older people. This paves the way for larger studies to explore the influence of lifestyle factors and biological sex in how people respond to dietary nitrate supplementation.”
Dr Lee Beniston FRSB, Associate Director for Industry Partnerships and Collaborative Research and Development at BBSRC, said:
“This research is a great example of how bioscience can help us better understand the complex links between diet, the microbiome and healthy ageing. By uncovering how dietary nitrate affects oral bacteria and blood pressure in older adults, the study opens up new opportunities for improving vascular health through nutrition. BBSRC is proud to have supported this innovative partnership between academic researchers and industry to advance knowledge with real-world benefits.”
The paper is titled ‘Ageing modifies the oral microbiome, nitric oxide bioavailability and vascular responses to dietary nitrate supplementation’ and is published in the journal Free Radical Biology and Medicine.