Tag: sex differences

Categories : NeurologyTags : Leave a comment

Sex Differences are Also Seen in Brain Immune Cells

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Image of an astrocyte, a subtype of glial cells. Glial cells are the most common cell in the brain. Credit: Pasca Lab, Stanford University
NIH support from: NINDS, NIMH, NIGMS, NCATS

New research from the University of Rochester finds that microglia function may not be as similar across sex as once thought. This discovery could have broad implications for how diseases like Alzheimer’s and Parkinson’s are approached and studied, and points to the necessity of having gender-specific research. It is already known that more women are diagnosed with Alzheimer’s and more men are diagnosed with Parkinson’s, but it’s unclear why.

Microglia are the immune cells of the central nervous system, clearing toxins in the brain. But if they are overactive, they can damage neurons instead and, in some cases, have been found to promote the progression of neurodegenerative diseases like Alzheimer’s and Parkinson’s. Although there are known sex-related differences in how microglia function, it was thought to be less variation in how they behave in adulthood. The new study showied how microglia respond differently in adult male versus female mice when given an enzyme inhibitor to block its microglia survival receptor.

“It is a fortuitous finding that has repercussions for what people are doing in the field, but also helps us understand microglia biology in a way that people may not have been expecting,” said Ania Majewska, PhD, professor of Neuroscience and senior author of the study in Cell Reports. “This research has a lot of ramifications for microglia biology and as a result all these diseases where microglia are important in a sex-specific manner.”

Pexidartinib or PLX3397 is an enzyme inhibitor commonly used to remove microglia in the lab setting to help researchers better understand the role of these cells in brain health, function, and disease. PLX3397 is also used to treat the rare disease tenosynovial giant cells tumours (TGCT), a condition that causes benign tumours to grow rapidly in the joints.

Researchers in the Majewska Lab were using PLX3397 in male versus female experiments but continued to run into difficulties, so they decided to take a different approach with the inhibitor. Instead of using it to ask other questions, they decided to better understand how microglia were responding to the drug in males versus females.

First author Linh Le, PhD (‘24), currently a Research Scientist, SetPoint Medical Corp, was a graduate student in the Majewska Lab when she found the expected response from microglia to PLX3397 in male mice: it blocked the receptor that signals microglial survival and depleted the microglia. However, Le, et al, were surprised to find that female microglia responded with a different signalling strategy that resulted in increased microglial survival and less depletion.

“These findings are crucial in the rapidly emerging field of developing disease-modifying therapies that target microglia,” said Majewska. “We do not yet know why the microglia are acting differently in the two sexes. I think we’d like to understand how the signaling through this receptor is regulated in different conditions, such as hormonal changes, basal state, inflammatory, or an anti-inflammatory state.”

Source: University of Rochester Medical Center

Categories : Injury & Trauma NeurologyTags : Leave a comment

Men More Than Three Times as Likely to Die From a Brain Injury, New Study Shows

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A new analysis of mortality data reveals the disproportionate impact of traumatic brain injuries (TBI) on older adults, males and certain racial and ethnic groups. The study, published in the peer-reviewed journal Brain Injury, provides a comprehensive analysis of TBI-related deaths across different population groups across the US in 2021.

The findings indicate that suicides remain the most common cause of TBI-related deaths, followed by unintentional falls, and specific groups are disproportionately affected by these tragedies.

Men, in particular, were found to be most likely to die from a TBI – more than three times the rate of women (30.5 versus 9.4). The reasons observed were multifactorial and could reflect differences in injury severity following a fall or motor vehicle crash, to the interaction of sex and age – with TBI outcomes in men worsening with age, while postmenopausal women fare better than men of similar age.

“While anyone is at risk for getting a TBI, some groups have a higher chance than others of dying from one. We identified specific populations who are most affected. In addition to men, older adults are especially at risk, with unintentional falls being a major cause of TBI-related death. American Indian or Alaska Native people also have higher rates of these fatal injuries,” says lead author Alexis Peterson PhD, of the National Center for Injury Prevention and Control at the Centers for Disease Control and Prevention.

“These findings highlight the importance of tailored prevention strategies to reach groups who may be at higher risk and the role healthcare providers can play in reducing TBI-related deaths through early intervention and culturally sensitive care.”

TBI remains a leading cause of injury-related death in the US In 2020, TBIs were associated with around a quarter of all injury-related deaths.

Using data from the National Vital Statistics System, the new analysis identified 69 473 TBI-related deaths among US residents during 2021. The age-adjusted TBI-related mortality rate was 19.5 per 100 000, representing an 8.8% increase from 2020.

Through statistical modeling, the researchers examined the simultaneous effect of multiple factors such as geographic region, sex, race and ethnicity, and age, on TBI-related mortality.

Key findings include:

  • Older adults (75+) had the highest rates of TBI-related deaths, with unintentional falls being the most common cause in this age group.
  • Non-Hispanic American Indian/Alaska Native individuals experienced the highest TBI-related death rate (31.5) compared to other racial and ethnic groups.
  • There were 37,635 TBI-related deaths categorised as unintentional injuries (ie, motor vehicle crashes, unintentional falls, unintentionally struck by or against an object, other).
  • 30,801 were categorized as intentional injuries (ie, all mechanisms of suicide and homicide).
  • Children aged from birth to 17 years accounted for around 4% of TBI-related deaths (2,977).

The authors emphasise the critical role of healthcare providers in preventing TBI-related deaths, particularly with groups at higher risk. “By assessing patients who may be at higher risk for TBI, especially due to falls or mental health challenges, healthcare providers can make timely referrals and recommend culturally tailored interventions to prevent further injury or death,” says Dr Peterson.

Public health efforts should focus on addressing the underlying causes of TBI-related deaths, such as unintentional falls and mental health crises, to help prevent further loss of life. “TBIs remain a significant public health concern, especially among older adults, men, and certain racial and ethnic groups,” says Peterson.  “CDC has proven resources that healthcare providers can use to not only reduce health disparities that increase the risk for TBI but also improve care for anyone affected by a TBI.”

The authors note the COVID-19 pandemic could have influenced TBI-related death trends in 2021. They also acknowledge several limitations of this analysis, including potential misclassification or incomplete documentation of causes on death certificates, which may lead to inaccuracies in estimating TBI-related deaths.

Source: Taylor & Francis Group

Categories : Gender NeurologyTags :

Sex Differences in Brain Structure Present at Birth

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Sex differences in brain structure are present from birth, research from the Autism Research Centre at the University of Cambridge has shown.

While male brains tended to be greater in volume than female brains, when adjusted for total brain volume, female infants on average had significantly more grey matter, while male infants on average had significantly more white matter in their brains.

Grey matter is made up of neuron cell bodies and dendrites and is responsible for processing and interpreting information, such as sensation, perception, learning, speech, and cognition.  White matter is made up of axons, which are long nerve fibres that connect neurons together from different parts of the brain. 

Yumnah Khan, a PhD student at the Autism Research Centre, who led the study, said: “Our study settles an age-old question of whether male and female brains differ at birth. We know there are differences in the brains of older children and adults, but our findings show that they are already present in the earliest days of life.

“Because these sex differences are evident so soon after birth, they might in part reflect biological sex differences during prenatal brain development, which then interact with environmental experiences over time to shape further sex differences in the brain.”

One problem that has plagued past research in this area is sample size. The Cambridge team tackled this by analysing data from the Developing Human Connectome Project, where infants receive an MRI brain scan soon after birth. Having over 500 newborn babies in the study means that, statistically, the sample is ideal for detecting sex differences if they are present.

A second problem is whether any observed sex differences could be due to other factors, such as differences in body size.  The Cambridge team found that, on average, male infants had significantly larger brain volumes than did females, and this was true even after sex differences in birth weight were taken into account.

After taking this difference in total brain volume into account, at a regional level, females on average showed larger volumes in grey matter areas related to memory and emotional regulation, while males on average had larger volumes in grey matter areas involved in sensory processing and motor control.

The findings of the study, the largest to date to investigate this question, are published in the journal Biology of Sex Differences.

Dr Alex Tsompanidis who supervised the study, said: “This is the largest such study to date, and we took additional factors into account, such as birth weight, to ensure that these differences are specific to the brain and not due to general size differences between the sexes.

“To understand why males and females show differences in their relative grey and white matter volume, we are now studying the conditions of the prenatal environment, using population birth records, as well as in vitro cellular models of the developing brain. This will help us compare the progression of male and female pregnancies and determine if specific biological factors, such as hormones or the placenta, contribute to the differences we see in the brain.”

The researchers stress that the differences between males and females are average differences.

Dr Carrie Allison, Deputy Director of the Autism Research Centre, said: “The differences we see do not apply to all males or all females, but are only seen when you compare groups of males and females together. There is a lot a variation within, and a lot of overlap between, each group.”  

Professor Simon Baron-Cohen, Director of the Autism Research Centre, added: “These differences do not imply the brains of males and females are better or worse. It’s just one example of neurodiversity. This research may be helpful in understanding other kinds of neurodiversity, such as the brain in children who are later diagnosed as autistic, since this is diagnosed more often in males.”

The research was funded by Cambridge University Development and Research, Trinity College, Cambridge, the Cambridge Trust, and the Simons Foundation Autism Research Initiative.

Reference
Khan, Y.T., Tsompanidis, A., Radecki, M.A. et al. Sex differences in human brain structure at birth. Biol Sex Differ; 17 Oct 2024; DOI: 10.1186/s13293-024-00657-5

Republished under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

Source: University of Cambridge

Categories : Cardiovascular Disease ExerciseTags :

Bursts of Activity could Cut Heart Risk in Women

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An average of four minutes of incidental vigorous physical activity a day could almost halve the risk of major cardiovascular events, such as heart attacks, for middle-aged women who do not engage in structured exercise, according to new research from the University of Sydney, published in the British Journal of Sports Medicine.

“We found that a minimum of 1.5 minutes to an average of 4 minutes of daily vigorous physical activity, completed in short bursts lasting up to 1 minute, were associated with improved cardiovascular health outcomes in middle-aged women who do no structured exercise,” said lead author Professor Emmanuel Stamatakis, Director of the Mackenzie Wearable Hub at the Charles Perkins Centre and the Faculty of Medicine and Health.

High-intensity physical activity that forms part of a daily routine is known as “vigorous intermittent lifestyle physical activity” (VILPA). Physical activity is incidental such as walking to the shops, vs exercise, which is structured, eg going to the gym. Longer sessions of VILPA are linked to significantly lower cardiovascular disease risk.

The researchers say that, given fewer than 20% of middle-aged or older adults engage in regular structured exercise, engaging in VILPA could be a good alternative.

“Making short bursts of vigorous physical activity a lifestyle habit could be a promising option for women who are not keen on structured exercise or are unable to do it for any reason. As a starting point, it could be as simple as incorporating throughout the day a few minutes of activities like stair climbing, carrying shopping, uphill walking, playing tag with a child or pet, or either uphill or power walking,” said Professor Stamatakis.

The study drew on UK Biobank data from 22 368 participants (13 018 women) aged 40–79 who reported they did not engage in regular structured exercise and who wore physical activity trackers for almost 24 hours a day for 7 days.

Cardiovascular health was monitored through hospital and mortality records, tracking major adverse cardiovascular events (MACE), such as heart attack, stroke, and heart failure, until November 2022.

After adjusting for factors such as lifestyle, socioeconomic position, cardiovascular health, co-existing conditions, and ethnicity, the researchers found that the more VILPA women did, the lower their risk of a major cardiovascular event.

Women who averaged 3.4 minutes of VILPA daily were 45 percent less likely to experience a major cardiovascular event. They were also 51% less likely to have a heart attack and 67 percent less likely to develop heart failure than women who did no VILPA.

Even when amounts of daily VILPA were lower than 3.4 minutes they were still linked to lower cardiovascular event risk. A minimum of 1.2 to 1.6 minutes of VILPA per day was associated with a 30 percent lower risk of total major cardiovascular events, a 33 percent lower risk of heart attack, and a 40 percent lower risk of heart failure.

However, men reaped fewer benefits from tiny bursts of VILPA. Those who averaged 5.6 minutes daily were only 16% less likely to experience a major cardiovascular event compared with men who did none. A minimum of 2.3 minutes per day was associated with only an 11% risk reduction.

Professor Stamatakis said more testing was needed to understand how VILPA may improve cardiovascular health.

“To date, it hasn’t been clear whether short bursts of VILPA lower the risk of specific types of cardiovascular events, like heart attack or stroke. We aimed to identify minimum daily thresholds and feasible amounts for testing in community programs and future trials,” he said.

“Importantly, the beneficial associations we observed were in women who committed to short bursts of VILPA almost daily. This highlights the importance of habit formation, which is not always easy. VILPA should not be seen as a quick fix – there are no magic bullets for health. But our results show that even a little bit higher intensity activity can help and might be just the thing to help people develop a regular physical activity – or even exercise – habit,” he said.

For the purposes of this story, physical activity is incidental, eg carrying shopping or briefly power walking, and exercise is structured, eg going to the gym or playing sport.

Source: University of Sydney

Categories : Substance UseTags :

Long Ring Fingers are Associated with a Preference for Alcohol

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People’s finger lengths may hold a vital clue to their drinking habits, a new study suggests. There is evidence that alcohol consumption is influenced by prenatal sex steroids – so experts from Swansea University and colleagues from the Medical University of Lodz decided to use a sample of students for their research into the subject.

Their findings, published in the American Journal of Human Biology, revealed relationships between high alcohol consumption and long 4th  digits (ring fingers) relative to 2nd  digits (index fingers). This showed that high prenatal testosterone relative to oestrogen is linked to high student alcohol consumption.

Professor John Manning said: “Alcohol consumption is a major social and economic problem. Therefore, it is important to understand why alcohol use shows considerable differences across individuals.”

The study used a sample of 258 participants – 169 of them female  –  and it revealed consumption rates varied between the sexes. In comparison to women, men show higher alcohol consumption and higher mortality from alcohol abuse.

He said: “A pattern like this suggests an involvement of sex hormones, such as testosterone and oestrogen. Digit ratio (2D:4D: the relative lengths of the 2nd and 4th fingers) is thought to be an index of early testosterone (long 4th digit) and oestrogen (long 2nd digit).

“It is known that alcohol-dependent patients have very long 4th digits relative to their 2nd digits, suggesting high testosterone relative to oestrogen exposure before birth. As expected, the associations were stronger for men than women.”

Now the researchers hope their conclusions will bring a better understanding of the factors underlying the pattern of alcohol consumption, from abstinence to occasional use to harmful dependence. 

This is the latest paper which has highlighted Professor Manning’s work in the field of digit ratios. Previous research  has examined how digit ratio may provide vital information concerning outcomes after contracting Covid-19, as well as oxygen consumption in footballers.

Source: University of Swansea

Categories : Gender Pain ManagementTags :

Men and Women Use Different Biological Systems to Reduce Pain

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In a new study evaluating meditation for chronic lower back pain, researchers at University of California San Diego School of Medicine have discovered that men and women utilise different biological systems to relieve pain. While men relieve pain by releasing endogenous opioids, the body’s natural painkillers, women rely instead on other, non-opioid based pathways. The study was published in PNAS Nexus.

Synthetic opioid drugs, such as morphine and fentanyl, are the most powerful class of painkilling drugs available. Women are known to respond poorly to opioid therapies, which use synthetic opioid molecules to bind to the same receptors as naturally-occurring endogenous opioids. This aspect of opioid drugs helps explain why they are so powerful as painkillers, but also why they carry a significant risk of dependence and addiction.

“Dependence develops because people start taking more opioids when their original dosage stops working,” said Fadel Zeidan, PhD, professor of anaesthesiology and Endowed Professor in Empathy and Compassion Research at UC San Diego Sanford Institute for Empathy and Compassion. “Although speculative, our findings suggest that maybe one reason that females are more likely to become addicted to opioids is that they’re biologically less responsive to them and need to take more to experience any pain relief.”

The study combined data from two clinical trials involving a total of 98 participants, including both healthy individuals and those diagnosed with chronic lower back pain. Participants underwent a meditation training program, then practiced meditation while receiving either placebo or a high-dose of naloxone, a drug that stops both synthetic and endogenous opioids from working. At the same time, they experienced a very painful but harmless heat stimulus to the back of the leg. The researchers measured and compared how much pain relief was experienced from meditation when the opioid system was blocked versus when it was intact.

The study found:

  • Blocking the opioid system with naloxone inhibited meditation-based pain relief in men, suggesting that men rely on endogenous opioids to reduce pain.
  • Naloxone increased meditation-based pain relief in women, suggesting that women rely on non-opioid mechanisms to reduce pain.
  • In both men and women, people with chronic pain experienced more pain relief from meditation than healthy participants.

“These results underscore the need for more sex-specific pain therapies, because many of the treatments we use don’t work nearly as well for women as they do for men,” said Zeidan.

The researchers conclude that by tailoring pain treatment to an individual’s sex, it may be possible to improve patient outcomes and reduce the reliance on and misuse of opioids.

“There are clear disparities in how pain is managed between men and women, but we haven’t seen a clear biological difference in the use of their endogenous systems before now,” said Zeidan. “This study provides the first clear evidence that sex-based differences in pain processing are real and need to be taken more seriously when developing and prescribing treatment for pain.”

Source: University of California – San Diego

Categories : Gender Obstetrics & GynaecologyTags :

Boy or Girl? This Genetic Mutation Increases Odds of Having a Daughter

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Each year, roughly the same numbers of boys and girls are born. But in individual families, some couples have four or more daughters and no sons, and some have all male children and no female children, points out University of Michigan evolutionary geneticist Jianzhi Zhang. This has led some scientists to question whether this skewed sex ratio is a result of the genes of the parents.

Now, Zhang and U-M doctoral student Siliang Song have detected a human genetic variant that influences the sex ratio of children. Additionally, they found that many hidden genetic variants of sex ratio may exist in human populations. Their results are published in the Proceedings of the Royal Society B: Biological Sciences.

“Scientists have been pondering and researching a genetic basis for sex ratio for decades, yet no unambiguous evidence for a genetic variation that alters the human sex ratio from an approximately 50:50 ratio has been found,” said Zhang, professor of ecology and evolutionary biology.

Zhang says this has led some scientists to think that the human sex ratio is not subject to mutation.

“But this scenario seems unlikely, because almost all human characteristics are subject to mutation and genetic variation,” he said. “Instead, we think genetic variation of sex ratio is too difficult to detect because sex ratio is not measured precisely.”

That is, each person typically has a very small number of children, which can lead to large errors in the estimation of the true sex ratio of a person’s children. For example, if a person only has one child, the estimated sex ratio would be either zero (if it’s a girl) or 1 (if it’s a boy) even if the true sex ratio is 0.5.

To detect genetic influence on sex ratio, the researchers realised they needed a much larger sample than in all previous studies. They turned to the UK Biobank, a biomedical database that contains the genetic and phenotypic information of about 500 000 British participants.

Analysing this data, the researchers identified a single nucleotide change named rs144724107 that is associated with a 10% increase in the probability of giving birth to a girl as opposed to a boy. But this nucleotide change is rare among the UK Biobank participants: About 0.5% of the participants carry this change. The nucleotide change is located near a gene named ADAMTS14, which is a member of the ADAMTS gene family known to be involved in spermatogenesis and fertilisation. The researchers also note that their discovery has not yet been confirmed in other samples.

The researchers also identified two genes, called RLF and KIF20B, that may also influence the sex ratio.

The study’s findings align with a theory in evolutionary biology called Fisher’s principle, which states that natural selection favours the genetic variant that increases the births of the rare sex. That is, if fewer males than females are born in a population, natural selection favours genetic variants that increase the number of males born, and vice versa. As a result, this selection yields a more or less even sex ratio in the population

“For Fisher’s principle to work, there must be mutations that influence the sex ratio,” Zhang said. “The fact that no genetic variation on human sex ratio had been identified has led some scientists to question the applicability of Fisher’s principle in humans.

“Our study shows that in fact, human data are consistent with Fisher’s principle and the reason no genetic variants of sex ratio had been discovered was the imprecision of the measure of a person’s offspring sex ratio.”

Next, the researchers hope to verify their findings in other samples – not an easy task, Zhang says, because of the large sample size requirement and the rareness of the identified genetic variant.

Source: University of Michigan

Categories : Diet and NutritionTags :

Avo at Breakfast for Women, Oats for Men, Study Suggests

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New research from the University of Waterloo suggests that men and women should have different kinds of food for breakfast in order to help lose weight.

The study, which employed a mathematical model of men’s and women’s metabolisms, showed that men’s metabolisms respond better on average to a meal laden with high carbohydrates like oats and grains after fasting for several hours, while women are better served by a meal with a higher percentage of fat, such as omelettes and avocados. The findings are out now in Computers in Biology and Medicine.

“Lifestyle is a big factor in our overall health,” said Stéphanie Abo, an Applied Mathematics PhD candidate and the lead author of the study. “We live busy lives, so it’s important to understand how seemingly inconsequential decisions, such as what to have for breakfast, can affect our health and energy levels. Whether attempting to lose weight, maintain weight, or just keep up your energy, understanding your diet’s impact on your metabolism is important.”

The study builds on an existing gap in research on sex differences in how men and women process fat. “We often have less research data on women’s bodies than on men’s bodies,” said Anita Layton, a professor of Applied Mathematics and Canada 150 Research Chair in Mathematical Biology and Medicine.

“By building mathematical models based on the data we do have, we can test lots of hypotheses quickly and tweak experiments in ways that would be impractical with human subjects.”

“Since women have more body fat on average than men, you would think that they would burn less fat for energy, but they don’t,” said Layton. “The results of the model suggest that women store more fat immediately after a meal but also burn more fat during a fast.”

Going forward, the researchers hope to build more complex versions of their metabolism models and extend beyond the consideration of biological sex by incorporating an individual’s weight, age, or stage in the menstrual cycle.

Source: University of Waterloo

Categories : CancerTags :

How, When and Where: Sex Matters in Melanoma Development

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Melanoma rates differ consistently between men and women in terms of the ages at which melanomas occur and the locations on the body where they occur. Over time, melanoma rates have increased in both men and women, but the trends differ by body site. A new study in the Journal of Investigative Dermatology, published by Elsevier, presents the findings from a large-scale, long-term melanoma data analysis investigating incidence trends by age, sex, and anatomic site.

Lead investigator David C. Whiteman, MBBS, PhD, Cancer Control Group, QIMR Berghofer Medical Research Institute, and Faculty of Medicine, The University of Queensland, Brisbane, Australia, explains, “There has been a general observation in numerous populations that melanomas appear to arise at different rates in men and women. We decided to investigate this observation rigorously and assess whether these differences have been constant through time or across generations by using large-scale data from population registries to investigate long-term melanoma trends in men and women.”

The research team analysed more than 40 years of melanoma data from Queensland, Australia, the USA, and Scotland. These three populations were chosen because historically they have had high (Queensland), moderate (USA), and low (Scotland) rates of melanoma. Over time, the rates of melanoma increased in all three populations, especially among women. In women in all populations, melanomas arise most commonly on the limbs, whereas in men, melanomas arise most commonly on the trunk and head and neck. In both sexes, there has been a steady increase in melanomas on the head and neck with increasing age.

Researchers found that in virtually all investigated populations, women experience higher rates of melanoma than men in early life (up to age ~45 years), but men develop melanomas at higher rates than women later in life (from ages ≥ 65 years). Furthermore, these sex-specific trends reflect complex patterns of incidence across body sites that vary consistently with age. Thus, in early life, women experience higher rates of lower limb melanomas than men, which persists into older ages. Also, on the upper limbs, women experience substantially higher rates than men from young ages until middle age (45–64 years), after which men experience higher rates. In contrast, on the head and neck and the trunk, melanomas occur at higher incidence in men than in women early in life. On all body sites, the rate at which melanoma incidence rises with age is much more rapid for men than for women.

The study confirms that men and women experience melanoma in different ways. While this is most likely driven by different patterns of sun exposure between men and women, there appear to be inherent differences in the ways in which melanomas develop at different body sites in women compared with men. Understanding the underlying biological differences could provide important clues about the etiology of this enigmatic cancer.

Source: Elsevier

Categories : Environmental Effects GenderTags :

Older Women more Vulnerable to Heat than Men, Researchers Find

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As global climate change causes extreme heat waves to become more common around the world, epidemiological studies have shown that heat kills more women than men. Now, a new study by researchers at Penn State has found that older women are physiologically more vulnerable to high heat and humidity than older men, and that women between the ages of 40 and 64 are as vulnerable as men 65 years of age or older. This is the first study to determine this disparity exists due to physiological differences rather than from a preponderance of women at old age due to greater longevity.

Led by Olivia Leach, doctoral candidate in kinesiology at Penn State, and her adviser, W. Larry Kenney, professor of physiology and kinesiology at Penn State, the researchers demonstrated that middle-aged and older women were affected by heat at lower temperature/humidity combinations than middle-aged and older men. The results, published in the American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, were somewhat unexpected, according to Leach, because there are no differences in heat vulnerability based on biological sex in adults younger than 30.

While the researchers did not directly compare middle-aged men to middle-aged women, the physiological responses of middle-aged women were similar to the responses of older men in the study, which demonstrated that middle-aged women are more vulnerable to heat than men of the same age.

“In addition to demonstrating that middle-aged and older women are at greater risk from extreme heat, we also identified what levels of heat and humidity are safe for women as they age,” Leach said. “This information is presented as a temperature/humidity curve based on a person’s age, and it can be useful for setting policies designed to keep people safe during a heat wave.”

The researchers tested the heat thresholds of 72 participants between 40 and 92 years of age in a specialized environmental chamber in Kenney’s laboratory. Before the experiment, participants swallowed a tiny device encased in a capsule that measured their core temperature throughout the experiment.

During the study, participants entered the specialised environmental chamber where they performed light physical activity to simulate the effort of minimal day-to-day tasks – the types of things people would need to do even during a heat wave. The researchers then gradually increased the temperature and/or humidity in the chamber until the participant’s body could no longer adequately cool itself, and their core temperature began to rise.

The study is part of the PSU HEAT, or Human Environmental Age Thresholds, project, led by Kenney. For five years, researchers in the PSU HEAT project have examined the levels of combined heat and humidity that humans can tolerate before their core temperatures begin to rise. When core temperatures rise, people become vulnerable to heat-related illnesses including heat exhaustion, heat stroke and even death.

“We’re not saying that people who experience a certain temperature will necessarily become sick or die,” Kenney said. “We are identifying the limits of livability – the thresholds where people can no longer continue their daily life unimpeded. Once people reach these temperatures, they need to take actions like seeking air conditioning to cool their bodies.”

Previous research by Kenney and others demonstrated that people become increasingly vulnerable to heat as they age, because their ability to efficiently sweat and pump blood to the skin – two primary cooling mechanisms – decreases. Sweat evaporation carries heat away from the body, while extra blood pumped to the skin dissipates heat to the environment and supports sweating.

To date, the PSU HEAT project has conducted more than 600 experiments on nearly 200 participants between ages 18 and 92, but the results of this experiment still yielded surprises, according to Leach.

“Among young adults, there is no difference in heat vulnerability between men and women,” Leach said. “Young people tend to be healthier, so any measurable health metric – from blood pressure to cholesterol – is more homogeneous among young people than it is among older people.”

As with other health measures, older adults have a wide range in their vulnerability to heat, Leach explained.

“We have examined many factors that might explain who faces the most risk in a heat wave,” Leach said. “We found that age and biological sex are the two most important factors that can predict whether a healthy adult would be at risk from high heat and humidity.”

While cardiovascular health and certain medications can affect a person’s sensitivity to heat, biological sex and age appear to be the two primary drivers of heat vulnerability among healthy people, the researchers said.

“Other factors – for example someone’s cardiovascular fitness or their body mass – have little impact on how vulnerable a person is to heat at rest or during light activity,” Leach continued. “Older women really are at greater risk from heat than other people. As governments and other social leaders prepare for extreme heat to become more common, the vulnerability of older women needs to factor into their planning.”

Source: Penn State