Category: Ageing

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‘Wait and See’: Three Words Costing Postmenopausal Women Their Hair

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More than half of postmenopausal women have clinically measurable hair loss. The most common response is to tell them to do nothing

Photo by Kateryna Hliznitsova on Unsplash

52% of postmenopausal women experience female-pattern hair loss, according to peer-reviewed research published in Menopause, the journal of the North American Menopause Society. Hot flushes – one of the symptoms that owns many public conversations about menopause – affect a larger proportion of women, but the disparity is not in the data. It is in how medicine responds to them. At more than one in two women, female-pattern hair loss is routinely absent from clinical consultations, rarely investigated at first presentation, and almost universally met with the same advice: give it time.

Why timing matters

During and after menopause, declining oestrogen levels and shifts in androgen balance cause susceptible hair follicles to gradually shrink. Each hair grows finer and shorter, with a briefer growth period per cycle. Left long enough without intervention, some follicles reach a point of no return, and the damage becomes irreversible.

“When we say irreversible, we mean that the follicle has become so damaged or inactive that it can no longer reliably regenerate a healthy terminal hair on its own,” says Dr Kashmal Kalan, Medical Director at Alvi Armani South Africa. “Medical therapies may help stabilise surrounding hair at that stage, but they may not recover what has already been lost,” says Dr Kalan.

For many women, that window closes not because they made an informed decision, but because nobody told them they had options. The advice they received – that gradual thinning is normal, that stress is a likely factor, that it may settle with time – sounded measured.

The cost of being dismissed

When the condition is classified as cosmetic, clinical urgency disappears. The patient is reassured rather than assessed, even though menopausal thinning is frequently a visible signal of systemic change. Hormonal shifts, nutritional deficiencies, thyroid dysfunction, and inflammatory or metabolic factors are all documented contributors, and none of them are cosmetic.

The consequences reach well beyond the scalp. Research published in the British Journal of Dermatology found that over 60% of women with hair loss actively avoided social interactions because of it. A separate study in the Journal of Cosmetic Dermatology found that affected women reported significantly higher social anxiety, lower self-esteem, and reduced life satisfaction compared to men experiencing the same condition. What begins on the scalp moves into how a woman presents professionally, how she engages socially, and how she sees herself.

A clinical framework built for men, applied to women

The protocols widely used to assess and treat this condition were largely developed around male patients. Defined hairline recession, concentrated donor areas, and linear progression are all considered male presentations. As a result, women have largely been assessed within a framework built for someone else.

“Applying male-based protocols to women can absolutely compromise outcomes. Female hair restoration requires an understanding of female-specific patterns of loss, progression risk, and the long-term hormonal picture. Preservation of softness, natural density gradients, and age-appropriate framing are considerations with no real equivalent in the male framework. In experienced hands, those distinctions are built into every stage of assessment and planning – not treated as secondary.”

What rigorous care looks like

At Alvi Armani, the first step is not a treatment recommendation – it is a diagnosis. A comprehensive workup, including blood investigations, is conducted before any intervention is discussed, because in menopausal women the drivers are rarely singular and what is visible on the scalp is seldom the whole picture.

“Not every patient is an immediate candidate for surgical restoration and recognising this is itself part of responsible practice. Medical stabilisation, non-surgical therapies, and hormonal management in collaboration with relevant specialists all form part of the treatment landscape – guided by individual diagnosis, not assumption,” Dr Kalan concludes.

“If any of this sounds familiar – the gradual changes, the concerns dismissed, the years of quietly adapting – it is worth knowing that the window is not necessarily closed. But it is also not standing still. Hair loss during menopause is extremely common – but common does not mean insignificant, and it does not mean inevitable.”

Categories : AgeingTags :

Genetic Trade-off Between Youth and Longevity Uncovered by Researchers

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A 3-month-old African turquoise killifish, left, and a 5-month-old killifish, right, show aging much like that in humans.

Researchers have identified a gene that directly links early-life growth and reproductive success with accelerated ageing and increased cancer risk later in life, offering new insight into a longstanding theory in evolutionary biology.

Now, an international team of researchers provides experimental evidence for the theory of antagonistic pleiotropy, the idea that certain genes can provide advantages early in life while contributing to disease and decline in old age.

What’s fascinating – and slightly terrifying – is that the cancer we see in these fish isn’t a random accident. It’s the direct shadow of their youthful vitality

Prof Itamar Harel

While widely accepted in theory, scientists have struggled to identify specific genes responsible for such trade-offs in vertebrates. Using the African turquoise killifish, a short-lived species recently pioneered by Harel and colleagues for genetic ageing research, the team focused on the gene vgll3, which has been previously linked to the timing of human puberty and maturation in other species, particularly Atlantic salmon.

By modifying this gene using CRISPR technology, the researchers observed clear effects. Fish with altered vgll3 grew faster and reached sexual maturity earlier, traits that could offer a reproductive advantage in natural environments.

However, these benefits came with significant long-term costs. The same fish showed reduced lifespans and a higher incidence of age-related tumours, including melanoma-like cancers.

“We have effectively caught evolution in the act of making a trade-off. For years, we’ve asked why our bodies can’t just maintain themselves indefinitely. This gene gives us a direct answer: nature doesn’t prioritise longevity; it prioritises continuity. We are built to sprint, not to marathon,” said Prof Itamar Harel at Hebrew University.

Further analysis showed that the gene influences key biological processes, including cell division, stem cell activity, and DNA repair. Increased cellular activity may help explain both the rapid development observed in younger fish and the accumulation of damage that leads to disease in older individuals.

The researchers also developed a new immunodeficient killifish model, enabling them to transplant and study tumour cells in ways not previously possible in this system.

“What’s fascinating – and slightly terrifying – is that the cancer we see in these fish isn’t a random accident. It’s the direct shadow of their youthful vitality. The same machinery that drives a cell to build a young body is hijacking the system to build a tumour in the old one. If we can understand this mechanism, we might finally learn how to decouple healthy growth from the disease of ageing,” Dr Harel added.

Because vgll3 is conserved in humans, the findings may have broader implications for understanding human development, ageing, and age-related diseases. While previous association studies have linked the gene to puberty timing and hormone levels, functional data were missing until now.

The discovery could contribute to future efforts in cancer prevention and research aimed at extending healthy lifespan. Researchers say the next step will be to explore whether it is possible to separate the gene’s beneficial early-life effects from its harmful consequences later in life.

Source: EurekAlert!

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Calcium and Vitamin D Supplements Offer Little to No Meaningful Benefit on Fracture and Fall Prevention

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Recommendations for calcium and vitamin D supplementation should be re-evaluated, suggest researchers

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Calcium, vitamin D, or combined supplements offer little to no clinically meaningful benefit on fracture and fall prevention in most older people, finds an in-depth review of the latest evidence published by The BMJ.

Almost a third of people aged 65 and older fall each year, often resulting in fractures, which are linked to pain, reduced quality of life, and the need for residential care. Preventing falls and fractures is therefore a global public health priority.

Several previous evidence reviews have found no reduction in fractures with either calcium or vitamin D supplements and results are inconsistent for combined use. The benefit of vitamin D on falls also remains unclear.

Yet despite this, many clinicians, guidelines, and regulatory agencies recommend vitamin D supplements (with or without calcium) for bone health, and prescriptions have increased substantially in recent years.

To address this uncertainty, researchers in Canada reviewed the results of 69 randomised controlled trials involving 153,902 adults that assessed the effect of calcium or vitamin D supplements – or a combination of both – on reducing the number of fractures and falls compared with placebo or no treatment.

The trials were of varying quality, but the researchers were able to assess their risk of bias and certainty of evidence using established tools.

After agreeing on clinically meaningful thresholds, the researchers found little to no effect for experiencing any fracture from use of calcium supplements (moderate certainty evidence from 11 trials; 9,067 participants), vitamin D supplements (high certainty evidence from 36 trials; 92 045 participants), or combined supplementation (high certainty evidence from 15 trials; 51 126 participants).

Calcium, vitamin D, or combined supplementation also appeared to have little to no effect on specific fractures, such as hip fractures, or falls, based largely on moderate to high certainty of evidence.

The researchers acknowledge that some analyses included a small number of trials and participants, so these findings should be interpreted with caution, and results may not apply to individuals with specific bone disorders or to those receiving drug treatment for osteoporosis.

However, the findings were consistent after further analyses to account for differences such as participant age, sex, history of fractures and falls, and average dietary calcium intake, supporting the strength of their conclusions.

As such, they say these findings “do not support routine supplementation with calcium or vitamin D, or combined supplementation to prevent fractures and falls” and they suggest clinicians, guideline panels, and regulatory agencies “should re-evaluate their general recommendations for calcium and vitamin D supplementation in light of current evidence.”

Evidence from rigorous and well-powered trials is needed to inform recommendations for supplementation in higher-risk groups, say researchers in a linked editorial.

In the meantime, they suggest that focus and funding should be redirected towards interventions that have been shown to offer meaningful prevention of falls and falls related injuries, such as balance and resistance exercise, and interventions that combine elements like exercise, hazard assessment or education, tailored to individual risk.

Source: The BMJ Group

Categories : Ageing Metabolic DisordersTags :

Choosing Safer Diabetes Medications for Older Adults

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Photo by Kampus Production

Older adults with type 2 diabetes face a difficult trade-off: they are among the most vulnerable to medication-related harms yet are often underrepresented in the clinical trials that guide treatment decisions. A new study led by Yuan Lu, ScD, helps address this gap by providing large-scale, real-world evidence about the safety of commonly used diabetes medications.

Published in Nature Communications, the study analysed data from more than 1.8 million people aged 65 and older across the United States and Europe. The researchers compared four major classes of second-line antihyperglycaemic medications – typically prescribed when first-line therapy such as metformin is not sufficient – across 18 safety outcomes.

“Evidence from clinical trials often does not fully capture older adults,” says Lu, assistant professor of medicine (cardiovascular medicine) at Yale School of Medicine. “They are more likely to experience side effects due to frailty, multiple chronic conditions, and the use of several medications at the same time.”

Newer diabetes drugs show overall safety advantages

The study found a consistent pattern: newer classes of medications, including GLP-1 receptor agonists and SGLT2 inhibitors, were generally associated with lower risks of several important adverse outcomes compared to older drugs such as sulfonylureas and DPP-4 inhibitors.

Newer agents were linked to lower risks of hypoglycaemia, hyperkalaemia, and peripheral oedema – complications that can be especially dangerous in older adults. However, the findings also highlight important trade-offs. For example, SGLT2 inhibitors were associated with a higher risk of diabetic ketoacidosis, while GLP-1 receptor agonists were more likely to cause gastrointestinal side effects such as nausea and vomiting.

Rather than identifying a single “best” medication, Lu emphasises that the results support more informed, individualised decision-making. “Some patients may have a higher risk of hypoglycaemia, while others may be more susceptible to diabetic ketoacidosis,” she says. “These risks need to be considered together as part of an individual patient profile.”

Real-world data at a global scale

A key strength of the study is its scale and approach. The analysis drew on nine large databases and was conducted through the Observational Health Data Sciences and Informatics (OHDSI), an international research network that enables standardized analyses across diverse health care systems.

By using harmonised real-world data and consistent analytic methods, the researchers were able to evaluate a broad range of safety outcomes in routine clinical practice – offering insights that complement and extend findings from randomised trials.

Supporting safer prescribing for an aging population

As the population ages and the use of newer diabetes medications continues to grow, understanding their safety profiles in older adults is increasingly important. The findings reinforce current guideline recommendations that often favour newer agents, while also underscoring the need to tailor treatment decisions to each patient’s risks and preferences.

Like all observational studies, the analysis cannot fully rule out unmeasured differences between patients. Still, the large, multinational design gives a more complete picture of medication safety in a population often underrepresented in clinical research.

Looking ahead, Lu and her colleagues hope to expand this work to examine the comparative safety of individual medications and to evaluate the safety of newer GLP-1 receptor agonists across a wider range of outcomes, including among people with obesity. “By providing more evidence in populations that clinicians see every day, our goal is to support safer, more informed care,” she says.

Source: Yale School of Medicine

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HEPA Air Purifiers May Boost Brain Power in Adults Over 40 – New Research

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Photo by Mari Lezhava on Unsplash

Nicholas Pellegrino, University of Connecticut; Doug Brugge, University of Connecticut, and Misha Eliasziw, Tufts University

Using an in-home HEPA purifier for one month spurs a small but significant improvement in brain function in adults age 40 and older. That’s the result of a new study we co-authored in the journal Scientific Reports.

HEPA purifiers – HEPA stands for high efficiency particulate air – remove particulate matter from the air. Exposure to particulate matter has been connected to respiratory and cardiovascular illnesses as well as neurological diseases such as Alzheimer’s and Parkinson’s. Environmental health researchers increasingly recommend that people use HEPA air purifiers in their homes to lower their exposure to particulate matter, but few studies have examined whether using them boosts mental function.

We analysed data from a study of 119 people ages 30 to 74 living in Somerville, Massachusetts. Somerville sits along Interstate 93 and Route 28, two major highways, resulting in relatively high levels of traffic-related air pollution. This makes it an especially good location for testing the health effects of air purifiers.

We randomly assigned participants to one of two groups. One used a HEPA air purifier for one month and then a sham air purifier – which looked and acted like the real thing but did not contain the air-cleaning filter – for one month, with a monthlong break in between. The second group used the real and sham purifiers in reverse order.

After each month, participants took a test that measured different aspects of their mental capacity. The test probed people’s visual memory and motor speed skills by measuring how quickly they could draw lines between sequential numbers, and it tested executive function and mental flexibility by asking them to draw lines between alternating sequential numbers and letters.

We found that participants 40 years and older – about 42% of our sample – on average completed the section testing for mental flexibility and executive function 12% faster after using the HEPA purifier than after using the sham purifier. That was true even when we accounted for factors like differences in the amount of time participants spent indoors, with either filter, as well as how stressful they found the test.

This improvement may seem small, but it is similar to the cognitive benefits that people experience from increasing their daily exercise. While you may not experience a sudden increase in clarity from a 12% boost, preventing cognitive decline is vital for long-term well-being. Even small decreases in cognitive functioning may be associated with a higher risk of death.

Studies increasingly show that air pollution can be detrimental to brain health.

Why it matters

Air pollution can negatively affect mental function after just a few hours of exposure. Studies show that air purifiers are effective at reducing particulates, but it’s unclear whether these reductions can prevent cognitive harm from ongoing pollution sources like traffic. Research has been especially lacking in people living near major sources of air pollution, such as highways.

People living near highways or major roadways are exposed to more air pollution and also experience higher rates of air pollution-related diseases. These risks aren’t encountered by all Americans equally: People of color and low-income people are more likely to live near highways or areas with heavy traffic.

Our study shows that HEPA air purifiers may offer meaningful health benefits under these circumstances.

What still isn’t known

Research shows that air pollution begins to affect cognitive function especially strongly around age 40. These effects may become increasingly prominent as people age.

HEPA air purifiers may therefore be especially beneficial for older adults. Our study did not explore this possibility, as fewer than 10 of our 119 participants were over the age of 60.

Also, our participants only used a HEPA air purifier for one month. It’s possible that longer durations of air purification may sustain or even increase the improvement in cognitive function we observed in our study.

Finally, it is unclear exactly how air purifiers improve cognition. Some studies suggest that exposure to particulate matter reduces the amount of the brain’s white matter, which helps brain cells conduct electrical signals and maintains connections between brain regions. The brain regions most harmed by air pollution are the ones that control mental flexibility and executive function, the same domains in which we saw improvements in our study.

We plan to study whether reducing particulate matter by using air purifiers is indeed protecting the brain’s white matter, and whether it could reverse some cognitive decline. We will explore that possibility by studying how levels of molecules called metabolites, which cells produce as they do their jobs, change in response to breathing polluted air and air cleaned by a HEPA filter.

The Research Brief is a short take on interesting academic work.

Nicholas Pellegrino, Research Associate in Public Health Sciences, University of Connecticut; Doug Brugge, Professor of Public Health Science and Community Medicine, University of Connecticut, and Misha Eliasziw, Associate Professor of Biostatistics, Public Health and Community Medicine, Tufts University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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Alzheimer’s Risk Gene APOE4 Silently Undermines Bone Quality in Women

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Buck Institute researchers discover a surprising connection between a major risk factor for Alzheimer’s

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Scientists at the Buck Institute for Research on Aging, along with collaborators at UC San Francisco, have discovered that APOE4, the most common genetic risk factor for Alzheimer’s disease, causes bone quality deficits specifically in female mice, through a mechanism that is invisible to standard imaging and can emerge as early as midlife.

The findings, published in Advanced Science, reveal an unexpected biological link between Alzheimer’s risk and skeletal health, and identify a new molecular pathway that could one day inform earlier diagnosis of cognitive decline or guide treatment for bone quality loss in women who carry the APOE4 gene.

“What makes this finding so striking is that bone quality is being compromised at a molecular level that a standard bone scan simply will not catch,” says Buck professor Birgit Schilling, PhD, a senior author of the study. “APOE4 is quietly disrupting the very cells responsible for keeping bone strong, and it is doing this specifically in females, which mirrors what we see with Alzheimer’s disease risk.”

Physicians have long observed that people with Alzheimer’s disease suffer bone fractures at higher rates, and that a diagnosis of osteoporosis in women is actually the earliest known predictor for Alzheimer’s. But the underlying mechanism connecting brain and bone health has remained elusive.

To investigate this connection, researchers, led by research scientist and co-first author of the paper Charles Schurman, PhD, first performed a proteomic analysis of aged mouse bone, a comprehensive survey of all the proteins present in the tissue. “The team discovered that bone, and particularly osteocytes, the long-lived cells embedded within it, is unusually rich in proteins associated with neurological disease, including apolipoprotein E [APOE] and amyloid precursor protein,” says Schurman. “Notably, APOE expression in osteocytes was twice as high in aged female mice as in young or male mice.”

The team then turned to a humanised mouse model carrying either APOE2 (associated with reduced Alzheimer’s risk), APOE3 (considered neutral), or APOE4 (the risk variant), and analysed bone and hippocampal tissue from the same animals. APOE4 produced strong, sex-specific effects on both the bone transcriptome and proteome; researchers found the protein-level disruption in bone was actually more pronounced than the corresponding changes in the hippocampus.

Despite the protein level disruption, cortical bone structure appeared normal under imaging. Researchers found that bone quality deficits arose not from changes in bone shape or density, but from APOE4’s suppression of perilacunar/canalicular remodelling, the process by which osteocytes actively maintain the microscopic channels that keep bone mechanically resilient. When this maintenance breaks down, bone quality deteriorates even when it looks intact.

“These results suggest that osteocytes could serve as early biological sentinels for age-related cognitive decline in women carrying APOE4,” says professor Lisa Ellerby, PhD, also a senior author of the paper. The Ellerby lab studies genetic risk factors for Alzheimer’s.  “We think that targeting osteocyte function may open a new front in preserving bone quality in this population.”

Researchers say there is a larger takeaway from this research that links brain and bone science.  “While we think this work is relevant for human patients with Alzheimer’s disease or with osteoporosis, this study also highlights the need for researchers to consider the human body as an entire system without isolating organs and diseases from each other,” says Ellerby.

Source: Buck Institute for Research on Aging

Categories : AgeingTags :

Physical Activity and Appropriate Sleep Linked to Subsequent Lower Dementia Risk

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Meta-analysis including millions of middle-aged to older adults supports recommended activity and sleep duration to reduce dementia risk

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Regular physical activity and getting the recommended amount of sleep may reduce dementia risk later in life, according to a new study by Akinkunle Oye-Somefun and colleagues of York University, Canada, published April 8, 2026 in the open-access journal PLOS One.

An estimated 55 million people live with dementia worldwide, and both its prevalence and cost are expected to increase, with global costs projected to reach $2 trillion dollars by 2030. Current treatments for preventing or treating dementia have limited efficacy; therefore, public health efforts have also aimed at healthy lifestyle factors to reduce the risk of dementia before symptoms occur. Healthy behaviours such as regular physical activity and good sleep hygiene are known to support cognitive health; however, there remains a need to better understand their relationship to dementia.

In this systematic review and meta-analysis, researchers analysed data from 69 prospective cohort studies representing millions of community-dwelling adults aged 35+, to see if there was a link between the development of dementia and three lifestyle behaviours: physical activity, sedentary behaviour, and sleep duration. Each of the observational studies recorded behaviours of cognitively healthy participants, then followed up at a later timepoint to report subsequent rates of dementia.

Overall, the meta-analysis found that regular physical activity, less sedentary time, and appropriate nightly sleep (7–8 h) were associated with a lower subsequent risk of dementia. Regular physical activity was associated with an average 25% lower risk of dementia among the 49 studies analysed; however, the researchers note that there was considerable heterogeneity between the studies.

Too little sleep (< 7 h) or too much sleep (> 8 h) was associated with an 18% and 28% higher subsequent risk of dementia, respectively, compared to optimal nightly sleep of 7–8 hours, though there was again considerable heterogeneity among the 17 studies analysed. Prolonged sitting (> 8 hours per day) was associated with a 27% higher risk of dementia among the three relevant studies analysed.

The study is consistent with and expands on previous research, using a large, diverse population with long follow-up times. While the study design cannot show any causative link between physical activity, sleep and dementia, the findings suggest an association between adherence to recommended physical activity and sleep levels in middle- and older-age adults and lowered dementia risk later in life.

The authors add: “Dementia develops over decades, and our findings suggest that everyday behaviours such as physical activity, time spent sitting, and sleep duration may be linked to dementia risk. Understanding how each of these behaviours relates to risk over time may help researchers identify opportunities to support brain health across the life course.”

“Separately, one aspect I personally found most interesting while conducting the study was the relatively limited evidence base on sedentary behaviour. Despite growing recognition that prolonged sitting is distinct from physical inactivity, we found only a small number of cohort studies examining its relationship with dementia risk. This highlights an important gap for future research.”

Provided by PLOS

Categories : AgeingTags :

Can Optimism Protect Against Dementia?

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Photo by Seb [ P34K ] Hamel on Unsplash

Higher optimism is associated with a lower risk of developing dementia, according to a new study in the Journal of the American Geriatrics Society. 

In the analysis of data from the Health and Retirement Study, a nationally representative sample of older US adults, optimism was assessed using the validated Life Orientation Test-Revised in 9071 cognitively healthy individuals within 2 years of obtaining each person’s first measure of cognitive function. Dementia was assessed during up to 14 years of follow-up. 

A 1-standard deviation increase in optimism was associated with a 15% lower risk of developing dementia, after adjusting for age, sex, race/ethnicity, education, depression, and major health conditions. 

“Identifying optimism as a protective psychosocial factor highlights the potential value of optimism in supporting healthy aging,” the authors wrote. 

Source: Wiley

Categories : Ageing ExerciseTags :

An Active Middle Age Cuts Women’s Risk of Premature Death in Half

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Australian study tracking more than 11 000 women found that meeting exercise guidelines during midlife had strong benefits for mortality

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Women who consistently met physical activity guidelines throughout middle age had half the risk of dying from any cause compared to women who remained inactive, according to a new paper publishing March 26th in the open-access journal PLOS Medicine by Binh Nguyen of the University of Sydney, Australia, and colleagues.

Physical activity is known to provide numerous health benefits and to reduce the risk of chronic diseases and premature mortality. However, most prior studies have measured physical activity at only a single point in time, which fails to capture how activity levels change over time.

In the new study, researchers used data from 11 169 women born between 1946 and 1951 who enrolled in the Australian Longitudinal Study on Women’s Health. Participants were surveyed nine times between 1996 and 2019, approximately every three years. Data was collected on how often the women met the World Health Organization’s recommendation of at least 150 minutes of moderate-to-vigorous physical activity (MVPA) per week.

The researchers found that consistently meeting MVPA recommendations throughout midlife was associated with a relative risk of all-cause mortality that was half that of those who consistently did not meet the recommendations (relative risk: 0.50). In absolute terms, the incidence of death was 5.3% among women who consistently met guidelines versus 10.4% among those who consistently did not. The magnitude of effect appeared similar or even stronger for cardiovascular disease and cancer mortality, though greater uncertainty in those estimates made the findings less conclusive, possibly because fewer deaths from those causes were observed. The evidence for benefits of starting to meet recommendations later in midlife – at age 55, 60, or 65 – rather than throughout all of midlife was also uncertain and inconclusive.

The study was limited by the fact that physical activity was self-reported and that the study sample may not be representative of all mid-aged Australian women.

“This study supports the growing evidence that maintaining an active lifestyle in midlife provides health benefits,” the authors say. “Women should be encouraged to meet physical activity recommendations throughout mid-age to derive these benefits.”

Nguyen adds, “Staying active throughout midlife can make a real difference for women’s long-term health. Our study shows that maintaining recommended levels of physical activity over multiple years helps protect against early death.” 

Provided by PLOS

Categories : Ageing NeurologyTags :

Popular Anti-ageing Compound Causes Callosal Brain Damage

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Part of the brain disappears in mice treated with dasatinib and quercetin

The image shows a section of the brain of a mouse treated with dasatinib and quercetin. The bluish area is the corpus collosum. The dotted outline shows the part of the corpus collosum that is affected by the medication. (Image courtesy of Crocker Lab/UConn School of Medicine)

A two-drug combination frequently used in anti-ageing research causes brain damage in mice, University of Connecticut researchers report in the March 16 issue of PNAS. The findings should make doctors cautious about prescribing the drug combo prophylactically, but also suggest new ways to understand multiple sclerosis.

“When you administer this cocktail to an animal, young or old, the myelin is damaged, which makes it disappear. Even worse in the young animals” than in the aged ones, says UConn School of Medicine immunologist Stephen Crocker.

Myelin is the insulation around the nerves. When it disappears, nerves don’t work as well, and people can develop numbness, pain, and lose the ability to walk. They can also have problems thinking and remembering. Missing myelin is the primary cause of multiple sclerosis. And Crocker and his colleagues saw it happen to mice when treated with dasatinib+quercetin (D+Q) at doses often used to treat ageing-related inflammation and metabolic disorders.

D+Q is a popular combination of medicines in anti-ageing research. Many studies have shown it works to eliminate aged cells that contribute to inflammation and other age-related symptoms. It is being tested for a range of diseases, from type II diabetes to Alzheimer’s. People in the anti-ageing scene sometimes even use it off-label, though the medical community discourages this. Very few studies have looked at its effect on the brain.

Evan Lombardo ’23 (CLAS), currently a Dartmouth neuroscience graduate student, and Robert Pijewski ’21 PhD, now at Anna Maria College, were working in Crocker’s lab when they wondered if it was possible to rejuvenate the brains of people with multiple sclerosis, and potentially heal their symptoms, using D+Q. They tried it on mice, both young (6 to 9 months) and old (22 months), as well as on brain cells cultured in a dish in the lab. The brain cells were oligodendrocytes, the cells that are supposed to grow and maintain myelin.

The results were dramatic. Healthy mice have myelin surrounding the axons (nerve cells) in the brain. It looks like dark rings around the lighter axon (see figure 1, the left panel.) But the mice treated with D+Q had much less myelin around their axons after the treatment, and the damage was worse in the younger mice. The corpus callosum, a region that connects the cerebral cortex to other parts of the brain and is associated with a range of important functions, also disappeared in mice treated with D+Q. This is known to happen sometimes to people who received chemotherapy, and causes the symptoms sometimes referred to as “chemo brain.”

When the researchers looked closely at the damaged brain tissue, they found clues as to why the myelin had disappeared. The myelinating cells – oligodendrocytes – hadn’t died. They’d regressed into a juvenile form of themselves. And the metabolism of the cells was abnormal, too.

“We suspect the drugs are choking off energy the cells need, and the cells respond by reducing complexity, reverting to a younger state, but less functional,” Crocker says.

Interestingly, these cells that have reverted look very much like a distinct population of cells found in people with multiple sclerosis. It suggests that in multiple sclerosis, myelinating cells might come under stress and revert to a younger stage. It also means those cells might be able to recover. And that is what the researchers are working on now.

“If we can mimic this, we have an amazing opportunity to see if the cells can recover and repair the brain,” Crocker says.

Source: University of Connecticut