Studies on menopause have always had to cope with the date of the final menstrual period varying enormously, which blurred the data due to the variable onset ages. But a innovative technique finds a distinct ‘physiological cliff’ related to the onset of menopause – and significant changes for a decade and a half preceding it.
To get around the problem of the variable onset age of menopause, researchers made use of a computational method originally used for astronomy and applied it to map large-scale biomedical datasets by anchoring health markers to the final menstrual period.
By analysing hundreds of millions of laboratory tests from two independent populations, scientists uncovered a step-like physiological cliff across endocrine, skeletal, hepatic, renal, and lipid systems that coincides precisely with menopause. These abrupt physiological shifts – which are of course completely absent in male control cohorts – often signal an increased risk of disease and begin more than a decade before menstruation permanently ceases. Furthermore, the analysis demonstrates that menopausal hormone therapy significantly attenuates these abrupt biological disruptions, restoring postmenopausal test trajectories to resemble a smoother continuation of earlier health patterns.
Contrary to popular belief, the postmenopausal ovary is not defunct.
In a new, paradigm-shifting study of ovaries from 28 women, scientists at Northwestern University and the Buck Institute for Research on Aging found that in the decades after menopause the ovary remains biologically active and continues to remodel with age, showing increased inflammation and changes in tissue structure. The study also identified a molecular link between ovarian ageing and cancer.
The study was published on 14 October in Aging Cell.
“In the ovary, we reach a point of no return with respect to fertility in which it’s no longer producing eggs, and I would venture to say most people assume those ovaries are just sitting there doing nothing, similar to the appendix,” said co-corresponding author Francesca Duncan (associate professor of reproductive science in medicine, Northwestern University Feinberg School of Medicine; associate professor in residence, Buck Institute). “But that’s what makes this study very different.”
The findings challenge the notion that the ovary is an innocent bystander after reproduction ends, raising questions about whether it could play a more active role in ageing and chronic disease in women.
“The ovary is not just a reproductive organ,” said co-corresponding author Birgit Schilling (professor and director of the Mass Spectrometry Center, Buck Institute). “It really influences how somebody ages because it speaks to all these other organs, such as the brain, and also to the bone, and women after menopause experience often a lot of bone problems. So, we think there is a connection between all these organs.”
Women now routinely live for decades after menopause, making it increasingly important to understand what the ovary is doing during this long post-reproductive period, Duncan said.
“Is the ovary the canary in the coal mine in women?” said Duncan. “Could ageing in the ovary set off a cascade of changes that continues throughout the body as women get older?”
Duncan’s group previously found similar evidence of continued remodelling in postmenopausal ovaries of mice. When she embarked on that research and the current study in humans, she expected to see very little activity in the postmenopausal ovary.
“I was predicting that if we took a 50-year-old ovary, a 60-year-old ovary, a 70-year-old, an 80-year-old ovary, they would all look exactly the same, have no eggs, and basically be non-functional,” Duncan said. “The fact that across species we’re seeing this gives us confidence that this isn’t just some random event, but something truly meaningful is happening in the biology.”
What remains unknown is exactly what the ovary is doing after menopause and whether those changes are beneficial or harmful, Duncan said.
“Our data points to progressive ageing features in which the ovary appears to lose its original identity and ends up doing something different,” Duncan said. “We do not yet know if there’s ever a point in a woman’s life when this organ is no longer beneficial and it’s actually harmful. These results really point to the need to ask this question.”
To characterise the changes, Schilling’s team – spearheaded by Buck Institute staff scientist Mark Watson – used advanced proteomic technologies to analyse 5,812 protein groups in normal ovarian tissue from postmenopausal women aged 50 to 75.
Human ovarian tissue is difficult to obtain, making the 28 ovaries an unusually valuable collection. By focusing exclusively on women within a relatively narrow 25-year age range after menopause, the researchers examined molecular changes that continue during the postmenopausal years. The technology allowed examination of thousands of proteins across every sample and identification of patterns using multiple statistical approaches.
Those analyses showed that the ovary continues to change well after its reproductive life ends.
Ovaries from younger postmenopausal women had more proteins involved in maintaining cells and tissue structure, while older ovaries had more proteins associated with inflammation, immune activity and the ongoing breakdown and rebuilding of the extracellular matrix. The differences were most pronounced between ovaries from women in their 50s and those from women 70 and older.
“When we analysed the data in multiple different statistical ways, what became clear across all these methodologies is that the ovary was not stagnant,” Schilling said. “In fact, over the decades, there were quite dramatic differences in terms of some proteins’ levels would go up with age and some proteins’ levels would go down, which tells us this organ is quite dynamic.”
The ageing ovaries also showed some of the same molecular patterns seen in cellular senescence.
The findings build on a discovery Duncan’s lab made a decade ago. In 2016, the lab was the first to report that as ovaries age they become increasingly inflamed, fibrotic and stiff. Because cancer cells can thrive in collagen-rich, stiff environments, the scientists have been investigating whether these age-related changes could make the ovary more hospitable to cancer cells.
The new study provides a molecular view of that remodelling process later in life. As postmenopausal ovaries aged, proteins involved in maintaining tissue structure declined, while proteins involved in inflammation and reshaping the tissue environment became more prominent.
Although all the ovarian tissue in the study appeared normal and cancer-free, some proteins previously associated with ovarian cancer were more abundant in ageing ovaries, with the strongest signal among women in their 60s. The finding does not mean the ovaries were cancerous or precancerous, but suggests healthy ovarian ageing and ovarian cancer share some biological processes.
“It’s not that all postmenopausal women get ovarian cancer, but we know that that fibrotic inflammatory environment is certainly an environment that cancer cells prefer to home in on,” Duncan said. “This is all consistent with the idea that the ageing ovary is a potential third hit for ovarian cancer, with the first hit being genetic and the second hit being environmental. So can we target the ageing ovary therapeutically to lower the risk of ovarian cancer, or can we develop novel biomarkers of ovarian cancer?”
The findings do not answer whether healthy ovaries should ever be removed after menopause. Rather, they raise new questions about how the biological activity of the postmenopausal ovary might influence women’s health systemically and whether the observed changes contribute to disease or are features of normal ageing.
Study opens a window to a better understanding of cellular rejuvenation processes
Fluorescence microscopy images from the Brüstle Research Group, showing the neural stem cells.
Researchers from the University Hospital of Bonn and the University of Bonn have succeeded in dramatically rejuvenating human cells in vitro. The researchers directly reprogrammed erythroid precursors into neural stem cells, resetting epigenetic clocks.
For example, blood cells from an 80-year-old were transformed into stem cells with a molecular age of less than 20 years. Since this rejuvenation occurred gradually, it is well-suited for detailed investigation of the underlying mechanisms. The results have been published in Aging Cell.
“Using this method, we have directly converted red blood cell precursors into neural stem cells,” explains Prof Oliver Brüstle (Institute of Reconstructive Neurobiology, University Hospital Bonn). In previous studies, the Bonn researchers had already shown that neurons produced in this way form connections with existing neurons after transplantation into the brains of mice.
“In our current study, however, we focused on a different phenomenon: namely, the observation that cells become significantly rejuvenated during reprogramming,” emphasises Brüstle (also TRA Life & Health, University of Bonn). To measure this, they used molecular clocks.
The cells’ epigenetic clocks were significantly reset by the reprogramming. As a result, cells from an 80-year-old subsequently exhibited a molecular age of less than 20 years. “We also know that this epigenetic rejuvenation ensures that the cells actually behave like young cells,” says Brüstle.
It was already known that a rejuvenation effect can occur during cell reprogramming. However, it had previously only been observed when reprogramming took place in two steps: conversion of a blood cell into a pluripotent stem cell, followed by differentiation into a neural stem cell.
Rejuvenation occurs very rapidly with this two-step method. “In contrast, we converted blood cells directly into neural stem cells – that is, without first passing through the pluripotent cell stage,” said Brüstle. “In our approach, rejuvenation occurred gradually and could be tracked for over 100 days.”
This opens up a unique window into a better understanding of cellular rejuvenation processes. “Rejuvenation that extends over such a long period of time is ideal as an experimental model: Since the epigenetic clocks are slowly reset over several weeks, we can use this model to investigate which factors and active substances accelerate or slow down the rejuvenation process.”
This is particularly relevant for neuroscience, says Brüstle: “After all, age is the most important risk factor for neurodegenerative diseases such as Alzheimer’s.”
Research groups from the University Hospital of Bonn, the University of Bonn, and RWTH Aachen University participated in the study. The study was funded by the EU’s Horizon 2020 programme, the German Research Foundation (DFG), and the Federal Ministry of Research, Technology, and Space (BMFRT).
Older adults who follow healthy dietary patterns have blood biomarker levels associated with more favourable biological processes relevant to ageing. This is shown in a study from Karolinska Institutet published in the journal BMC Medicine. The findings may contribute to a better understanding of how dietary habits are related to the body’s ageing processes.
Researchers have long known that diet plays an important role in health later in life, but the biological mechanisms underlying these associations are not yet fully understood. In the current study, researchers cross-sectionally investigated how different dietary patterns are associated with a broad range of blood biomarkers reflecting metabolism, inflammation, vascular health and neurodegenerative processes related to ageing.
The study included 1,769 people aged 60 years and over who participated in the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K). Participants answered questions about their dietary habits over the previous year, and researchers simultaneously analysed 54 different blood biomarkers.
Three dietary patterns
The researchers examined three dietary patterns that have previously been linked to good health: a Mediterranean-style diet, an index of overall dietary quality, and a measure of the inflammatory potential of the diet. Greater adherence to these dietary patterns was associated with favourable levels of several biomarkers. This included higher folate levels and lower levels of growth differentiation factor 15, which were observed consistently across all three patterns. Additional associations with biomarkers linked to inflammation, metabolism and neurodegenerative processes were specific to individual dietary patterns.
“Our findings suggest that healthy dietary patterns are associated with several biological processes that are important for how we age. This reinforces the view of diet as a modifiable factor that may contribute to healthy ageing,” says Rachel Ann Da Costa, researcher at the Department of Neurobiology, Care Sciences and Society, and first author of the study.
The dietary pattern with lower inflammatory potential showed associations with the greatest number of biomarkers, particularly those linked to inflammation and metabolism. According to the researchers, this may indicate that the inflammatory properties of diet are related to several interconnected biological processes involved in ageing.
More studies needed
As the study examined associations at a single point in time, it cannot establish cause and effect. The researchers also emphasise that participants mainly consisted of older adults from the Stockholm area with relatively high levels of education, which may limit the generalisability of the findings to other populations.
“We now need more longitudinal and intervention studies to investigate whether changes in diet also lead to changes in the biological markers we have studied,” says Adrián Carballo-Casla, researcher at the same department and last author of the study.
The study was conducted in collaboration between researchers at Karolinska Institutet, Stockholm University, KTH Royal Institute of Technology, Stockholm Gerontology Research Center, Universidad Autónoma de Madrid and CIBERESP in Spain, as well as the University of Ljubljana in Slovenia. The study is based on data from SNAC-K. Funding was provided by, among others, the Swedish Research Council, Forte, Karolinska Institutet, the Swedish Alzheimer Foundation, the Dementia Foundation, the Foundation for Geriatric Diseases at Karolinska Institutet, the David and Astrid Hagelén Foundation, and Swedish government departments, regions and municipalities. The researchers report no conflicts of interest.
Three ways of measuring diet quality
Alternative Mediterranean Diet (AMED)
A dietary pattern based on the traditional Mediterranean diet. Higher scores are awarded for a high consumption of vegetables, legumes, fruit, nuts, whole grains and fish. A high proportion of unsaturated fats and moderate alcohol consumption are also scored positively. Lower consumption of red meat and dairy products likewise contributes to a higher score.
Alternative Healthy Eating Index (AHEI)
A scientifically developed index that measures overall diet quality. Higher scores are awarded for foods such as vegetables, fruit, whole grains, legumes, nuts, fish, healthy fats and moderate alcohol consumption. Lower scores are given for high consumption of red and processed meat, sugar-sweetened beverages, trans fats and sodium.
Empirical Dietary Inflammatory Index (EDII)
A measure that estimates how diet influences inflammation in the body. In this study, a reverse version of the index was used, with higher scores corresponding to a diet with lower inflammatory potential. Components such as leafy green and dark yellow vegetables, fruit juices, coffee and tea receive higher scores, while higher consumption of red and processed meat, refined grain products and sugar-sweetened beverages results in lower scores.
A study by DZNE finds that healthy eating is associated with slower biological aging – and that there is more than one way to eat healthily. The researchers examined ten dietary patterns considered healthy, including the Mediterranean, Nordic, and a plant-based diet, as well as the DASH diet, which is designed to help lower blood pressure. All were linked with slower biological aging, with age-related changes in the DNA serving as markers. These results, based on data from DZNE’s Rhineland Study and confirmed with data from an independent study, are published in the journal Nature Communications.
“Our study suggests that healthy eating goes hand in hand with slower biological aging. The effects are not massive, but they are measurable and relevant for prevention. By slowing the aging process, the risk of age-related diseases such as dementia or cardiovascular disorders can be reduced. Thus, healthy eating contributes to healthy aging,” says Prof. Monique Breteler, Director of Population Health Sciences at DZNE and head of the Rhineland Study. “Importantly, there is probably no single ‘correct’ diet. According to our data, various dietary patterns are associated with slower aging, some more, some less. That is an encouraging finding, because it leaves room to tailor healthy eating to personal and cultural preferences, budget and taste.”
Molecular Aging Measures
For their analysis, the researchers evaluated blood samples and dietary habits from about 7500 women and men: This included 6470 participants of DZNE’s Rhineland Study in Bonn – where the findings were initially made – and 1034 participants of the EPIC-Potsdam Study of the German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), where the key results were independently confirmed.
From blood, the team determined chemical modifications in the DNA, known as “DNA methylation patterns”, which influence gene activity and thus biological mechanisms. Since these molecular markers change systematically over the course of life, they are considered indicators of biological aging.
“We applied three different approaches, so-called epigenetic clocks, to read biological aging from DNA methylation,” explains Juliana Tavares, a doctoral researcher at DZNE and lead author of the current publication. “To this end, we leveraged state-of-the-art technology, which allowed us to cover about 850 000 sites in the DNA. This is roughly twice as many as in most previous studies.”
Healthy Eating: Different for Everyone
The researchers also matched every participant’s eating habits against the recommendations of each of the ten diets studied. Adherence was quantified and graded using a scoring system based on how closely individuals followed each dietary pattern. “One and the same person could therefore rank high on one diet score and low on another. In other words: People who ate healthily by one standard were often not the same people who ate healthily by another. According to our data, hardly anyone counts as a healthy eater by every standard at once,” says Tavares.
However, across the board, higher diet quality was associated with slower biological aging. This applied to all of the ten diets examined. “While there are measurably differences between the diets, they are modest in absolute terms. It’s the big picture what matters,” says Tavares. “In summary: When it comes to slowing down the aging process, there isn’t just one healthy diet, but indeed a whole repertoire of possible diets with a positive effect.”
One result was particularly noteworthy: the association between diet quality and slower biological aging was most pronounced in smokers, even though smokers were by no means eating healthier than non-smokers. The biological explanation is still open. “Smoking is very harmful to health,” says Tavares, “One explanation for our findings might be that there is just more health benefit to gain for smokers by eating healthy because of the enormous detrimental effects of smoking.”
Shared Biological Pathways
Although each dietary pattern was associated with its own distinct set of DNA methylation sites, the biological mechanisms involved showed substantial overlap. “More than 70 percent of the affected biological pathways were shared across all diets. These involve cell structure, cell signalling and metabolism – processes central to aging and chronic disease. Therefore, it is understandable that the dietary patterns we examined were all linked with a slowing of biological aging,” says Tavares. “A few pathways were diet-specific, and they matched each diet’s main objectives: heart-related pathways were unique to the DASH diet, and pathways related to cognition and memory were unique to the so-called MIND diet, which aims to support brain health. You don’t need a perfect diet – that may be the most practical message here. But moving forward, the diet-specific pathways point to future research on targeted dietary interventions. This could be helpful in designing targeted health recommendations.”
By Dianne Boyd – Chief Operating Officer Frail Care at Allmed
Photo by Kampus Production on Pexels
There is a quiet shift happening in homes across South Africa. As the population ages and hospitals grapple with packed wards and immense strain, families are looking closer to home for answers. More seniors are choosing to stay right where they are, surrounded by their own memories, familiar furniture, and beloved pets, rather than moving into frail care or assisted living facilities. At the same time, because hospitals are discharging patients much faster following surgery, strokes, or cancer treatments, expert recovery support right in the living room has never been more important.
For most people, the thought of healing or growing older in a familiar space brings an unmatched sense of comfort and dignity. But for someone navigating the fog of dementia or the daily weight of a chronic illness, holding onto familiar routines is life changing. It reduces anxiety, keeps confusion at bay, and gives patients a deep-seated feeling of control that a clinical institution simply cannot match.
The hidden trap of doing it alone
As the need for home care grows, it becomes easy to see why some families turn to online platforms or informal word-of-mouth recommendations to find help. On the surface, hiring a caregiver directly feels simpler, quicker, and perhaps cheaper. But it often masks a maze of hidden responsibilities and risks that families are rarely prepared for.
Society tends to think of home care as simple companionship or a helping hand with daily tasks. In reality, caring for a vulnerable loved one safely requires a tremendous amount of unseen work. When individuals hire someone independently, they suddenly step into the role of an employer. Managing contracts, payroll, UIF contributions, and leave becomes an immediate reality. Worse still, what happens when a caregiver wakes up sick or resigns unexpectedly? Without a reliable agency behind the household, finding cover at 4am in the morning falls entirely on the family.
Even more concerning are the clinical visibility gaps in such an arrangement. Without professional oversight, missing the subtle early warning signs of trouble is remarkably easy; a tiny pressure sore starting to form, the early stages of dehydration, a missed medication, or a silent infection.
Why professional care changes everything
Treating home-based care as a true healthcare partnership rather than a domestic arrangement completely changes the experience for a family. Reputable, registered providers shoulder the heavy burden of care, so relatives do not have to carry it alone.
Instead of crossing fingers and hoping for the best, a professional approach brings real clinical governance into the home. Experienced clinical facilitators step in to assess patient needs, create tailored daily care plans, and check in regularly. They ensure that caregivers are thoughtfully matched to the individual, such as pairing someone with specialised dementia training with a patient who needs calm, skilled behavioural guidance.
Partnering with an established provider also puts a safety net around the entire household. Professional agencies cover personnel with medical liability insurance while handling all statutory requirements like workmen’s compensation, keeping families legally and financially protected from unforeseen accidents.
Finding peace of mind and financial relief
One of the greatest barriers families face with home care can be the financial weight. This is where working with a registered provider can make a profound difference. Because established agencies hold an official practice number, families can often submit claims directly to their medical aid schemes, subject to scheme rules and a specialist’s clinical motivation. This can be a powerful way to ease the financial strain of long-term support.
Bringing care into the home should bring peace of mind rather than sleepless nights. Leaning on a professional team for the vetting, the legalities, and the clinical oversight allows relatives to step back from being managers and return to being sons, daughters, or partners. That leaves space to focus on what truly matters: sharing meaningful, comfortable moments with a loved one, right where they belong.
A new Ontario-wide study reveals that common medications, from statins to iron supplements, are quietly setting off prescribing cascades that leave older adults unknowingly taking drugs to treat side effects of other drugs.
The research, published in BMJ and led by Paula Rochon, a clinician scientist at Sinai Health and professor of medicine at the University of Toronto’s Temerty Faculty of Medicine, has revealed that certain drug combinations are a common but unrecognised contributor to drug related harm at the population level and add unnecessary costs to the healthcare system.
A potentially inappropriate prescribing cascade (PIPC) happens when a medication’s side effect gets mistaken for a new health problem, leading to another prescription that may not have been needed in the first place. One common example flagged in the study involves non-steroidal anti-inflammatory drugs (NSAIDs). Commonly prescribed for pain, these drugs are associated with a rise in blood pressure, which can lead to a new prescription for high blood pressure, rather than a second look at the original pain medication. Older adults are especially vulnerable to this pattern because they’re more likely to be on multiple medications at once, due to having multiple conditions, making it harder for both patients and clinicians to trace a new symptom back to an existing drug.
“These sequences of events are common but often missed in clinical practice,” says Rochon, who serves as the director of research at the Weston and O’Born Centre for Mature Women’s Health at Sinai Health. “Knowing what medications you are taking, when they were started and for what indication is important in order to identify possible prescribing cascades that may be problematic.”
The study brought together an interdisciplinary, international team of collaborators and leaders in drug prescribing and geriatric medicine research from the United States, Belgium, Italy, Israel and Ireland, along with Sinai Health researchers and U of T professors Vasily Giannakeas and Nathan Stall, geriatrician Christina Reppas-Rindlisbacher and research staff Wei Wu and Joyce Li.
With the expertise of 12 international panellists specialising in internal medicine, geriatric medicine and clinical pharmacology, the research team previously created a list of 65 PIPCs. Using this list and population-level prescription data from ICES, Ontario’s health data institute, the researchers examined each PIPC against three factors: how common the initial drug was in the population, how often it was followed by the second drug, and how strong the link was between the two. That analysis allowed them to pinpoint the 24 potentially inappropriate prescribing cascades most commonly seen in the population and with a potential to cause harm.
Seeing the pattern behind every prescription
For Rochon, the findings highlight a gap that opens quietly, one prescription at a time. “Our concern is that so often these conversations between the health care prescriber and the patient are being missed, so people don’t recognise the sequences of events and that they are connected to one another,” she said.
Closing that gap means physicians need to think about medication history at every visit, not just what a patient is currently taking, but why each drug was started in the first place, and whether the next one was really needed.
The work also carries a particular weight for mature women, as they tend to live with more chronic conditions than men over their lifetime. Mature women are prescribed more drug therapies, and experience more adverse drug events. By being on multiple medications at once, they are more exposed to the risk that a drug’s side effect gets mistaken for a new diagnosis rather than traced back to its source.
The team’s findings point to promising next steps.
The first involves technology. Automated clinical decision support tools could flag a prescribing cascade in real time and prompt a second look before a new prescription is added. This information could be leveraged in one of several automated ways to help clinicians be aware of these potentially inappropriate prescribing cascades at the point of care.
Next is optimising the role of pharmacists as part of the care team and more directly integrating them into the prescribing process alongside physicians. Their expertise can help identify these potentially inappropriate prescribing cascades for further evaluation.
A world-first clinical trial conducted by Monash University researchers has shown that cholesterol-lowering medication can reduce heart attack and stroke in people aged over 70 years.
Statins are commonly prescribed to manage high cholesterol in people up to 75 years, and are known to reduce the risk of heart attack and stroke. But until now it was unclear whether they were effective in older people.
New research from Monash University, published in the New England Journal of Medicine and presented concurrently at the European Society of Cardiology Congress 2026, found the medication decreases the risk of a first major cardiovascular event by 30 per cent for adults aged over 70 living independently.
The Statins in Reducing Events in the Elderly (STAREE) Trial is the first randomised controlled trial of statin therapy to examine whether the drugs could help in older people who have historically been overlooked in clinical trials.
This landmark, ten-year trial analysed the cardiovascular outcomes of almost 10 000 participants while they took either a statin or placebo.
Lead researcher Adjunct Professor Sophia Zoungas, from the Monash School of Public Health and Preventive Medicine, said the findings will change the way clinicians manage cardiovascular risk in older people.
“What we hope to see, now that we have provided such strong evidence, are updated treatment guidelines to help clinicians make use of this new finding,” Professor Zoungas said.
The global prevalence of cardiovascular disease is expected to almost double from 600 million in 2025 to more than one billion affected adults in 2050. An estimated 2 ,000 older Australians suffer from major cardiovascular events, like heart attack and stroke, each year. The risk increases with age, so people aged over 70 are automatically in a high risk category regardless of lifestyle or other factors.
“The risk of heart attack and stroke is a major concern for older people,” Professor Zoungas said. “Knowing there is a safe and effective measure for lowering that risk will be a huge reassurance to older people and their families.
“Anyone who has seen a loved one impacted by cardiovascular disease will know just how important prevention is.”
Co-author Professor Mark Nelson, a prominent general practitioner, Adjunct Professor at the Monash School of Public Health and Preventive Medicine and Research Fellow at Menzies Institute for Medical Research at the University of Tasmania, said this is critical evidence to support GPs in their decision-making around cardiovascular health in older people.
“This was a particularly important trial because it was conducted in the community, with more than 3400 GPs taking part across Australia,” Professor Nelson said. “In light of this new evidence, older patients should have a conversation with their GP about whether statins are an appropriate treatment for their cardiovascular health to help them remain fit and healthy.”
When Raghav Sehgal arrived at Yale as a graduate student several years ago, he wanted to explore the use of powerful computer science tools in cancer research. With an engineering background and a computational biology startup already under his belt, he was well prepared.
But as Sehgal began his Ph.D. studies, his thesis adviser at the Yale School of Medicine posed a larger question: If you want to solve cancer or any age-related disease, such as cardiovascular disease, why not solve aging itself?
“That put me on a different path,” said Sehgal, an associate research scientist in psychiatry with specialties in computational biology and bioinformatics. “As researchers, we have a long way to go in understanding the aging process and whether the steps we take to manage it really work.
What works and what doesn’t
Improved blood-based DNA tests indicate that these interventions seem to be the most effective at slowing the biological aging process:
Prescribed medications for metabolic control and weight management, including metformin and semaglutide.
Healthy diet and exercise combined. Researchers looked at popular diets including, the Mediterranean, low-fat, and low-carb plans.
Additional research is needed to further validate the findings.
Today, Raghav’s research focuses on the biological systems that drive human aging and how to best measure aging, as well as why aging gives rise to diseases like cancer, diabetes, and dementia. And while his research might not necessarily solve aging, he does explore whether the aging process can be reversed through interventions.
Sehgal is the first author of a new paper from the lab of Albert Higgins-Chen, assistant professor of psychiatry in the Yale School of Medicine. In the paper, Higgins-Chen’s research team took a significant step toward determining which existing anti-aging measures have quantifiable impacts.
Using a new class of DNA-based blood tests, they found that lifestyle interventions and certain drug treatments indeed appear to slow the aging process, while over-the-counter supplements don’t have much effect. All members of the Higgins-Chen lab collaborated in the work, including researchers Daniel Borrus, Jenel F. Armstrong, John Gonzalez, Jessica Kasamoto, and Yaroslav Markov. The paper appears in the journal Nature Medicine.
“For the first time we’ve shown that certain therapies have measurable impacts,” said Sehgal. “This wasn’t previously possible, because we didn’t have enough data to say these biomarkers are consistently responsive to these interventions.” Biomarkers are measurable indicators that reflect a person’s functional or biological age rather than just the number of years lived.
For their analysis, the researchers primarily used a type of blood-based biomarker known as epigenetic clocks, which estimate epigenetic or biological age by measuring the pattern of methyl groups (basic chemical structures that act like tags) attached to a person’s DNA. As people age, these chemical tags change, previous research has shown. Successful anti-aging interventions can reverse the tags. Computer algorithms are then able to use the changes observed in these tags to estimate a person’s epigenetic “age.”
In their work, the researchers combined data from 51 anti-aging intervention studies – which examined a range of strategies, from supplements to medical procedures – and measured more than 110 DNA methyl biomarkers (including 16 major epigenetic clocks). They then compared participants’ biological ages before and after various interventions.
“What we did was pretty unique,” Sehgal said. “We already know that certain things might prolong health span and lifespan. There is data from retrospective analysis as well as from animal models. We took all that knowledge along with the real-world clinical studies to identify which interventions in humans were slowing down aging across the board in these known biomarkers.”
The researchers tested four categories of intervention: pharmacological drugs, lifestyle-based changes, over-the-counter supplements, and medical procedures. They found that lifestyle interventions, such as a combination of a healthy diet (whether it’s Mediterranean, low-carb, or low-fat) and exercise, consistently decreased epigenetic age.
Pharmacologic interventions – including metformin and semaglutide, prescription medications used for metabolic control and weight management, and anti-TNF therapies, which use biologic medications to target an immune system protein that triggers harmful inflammation –decreased epigenetic age the most. (TNF, or tumour necrosis factor, is an immune-system protein that helps fight inflammation-related injury.)
On the other hand, over-the-counter supplements and certain medical procedures didn’t have an effect in decreasing epigenetic age, their analysis showed. Other key findings revealed that the newer biological age clocks outperformed older models, and that biomarkers changed more in people with diseases than in healthy volunteers.
Going forward, the next step would be expanded testing measuring interventions and impact in a widespread, diverse group of volunteers, Sehgal said.
“If these new biomarkers are eventually validated to predict long-term health, scientists will be able to evaluate anti-aging therapies much faster,” he added. “Instead of waiting decades for evidence from clinical trials, we’ll be able to see which interventions are effective and in which people in a few years or even months.”
Senior author Higgins-Chen warned that researchers need to be cautious in interpreting intervention studies.
“We have developed a rigorous, systematic approach to evaluating and comparing how biomarkers change across a wide variety of interventions, and that is a critical step in the right direction,” he said. “However, the true meaning of that change must be fully understood.”
Which biomarker changes are due to the intervention, and which result from hidden confounders? What is the time course of the change during an intervention – and after the intervention ends? What are the biological mechanisms underlying the change?
“And most importantly – what does the change mean for our long-term risk of age-related disease and functional decline?” Higgins-Chen said. The lab is continuing to investigate these questions in additional studies led by researchers Borrus, Armstrong and Grace Zou. Chen’s lab is also affiliated with the Department of Pathology, the Computational Biology and Bioinformatics Program, and the Y-Age Yale Center for Research on Aging.
Older adults who typically had longer intervals between meals accumulated chronic diseases more rapidly over time than those with shorter intervals, according to a study from Karolinska Institutet published in the Journal of Internal Medicine. The association was most pronounced among people aged 78 years and older.
Interest in fasting has increased in recent years, but relatively little is known about how meal timing affects health in older adults. In this new study, researchers investigated whether the duration of the longest daily interval between meals was associated with the accumulation of chronic diseases over time.
The researchers used data from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K), which includes 2,981 people in Stockholm who were aged 60 years or older at the start of the study. Participants were followed for up to 15 years. The duration of intervals between meals was estimated from participants’ self-reported information about when they typically ate during a 24-hour period.
Association seen across disease types
Longer intervals between meals were associated with faster accumulation of chronic diseases over time. In particular, people whose longest interval between meals during a typical day was 14 to 24 hours accumulated chronic diseases more rapidly than those whose longest interval was 6 to 11.5 hours. The association was observed for the total number of chronic diseases, as well as for cardiovascular and neuropsychiatric diseases, but not for musculoskeletal diseases.
“Much of the research on fasting has been conducted in younger or middle-aged populations. Our findings suggest that the associations may be different in older adults, particularly among the oldest age groups”, says Adrián Carballo Casla, last author of the study and postdoctoral researcher at the Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet.
The researchers emphasise that the study cannot determine cause and effect. Although longer intervals between meals were linked to faster disease accumulation, the study cannot establish whether the fasting pattern independently contributed to this outcome.
For information on funding and any potential conflicts of interest, please see the study.
