Daily Archives: 22 August 2024

Australians surpass their counterparts in affluent English-speaking nations by 1-4 years in lifespan

A study published in the open-access journal BMJ Open reveals that Australians live longer than their counterparts in five other high-income English-speaking countries, including the UK and the US, with a lifespan advantage of 1 to 4 years. The analysis, which scrutinised international longevity data from 1990 to 2019, shows that most of Australia’s longevity benefits range from 45 to 84. Australians generally experience lower mortality rates from issues such as drug and alcohol misuse, treatable cancers, and cardiovascular and respiratory diseases.

Despite significant gains in life expectancy during the 20th century across high-income nations, progress has slowed markedly since the beginning of the 21st century. This slowdown, even before the disruptions caused by the COVID-19 pandemic, is concerning. Factors contributing to this include plateauing reductions in cardiovascular disease deaths and increases in fatalities related to drug overdoses, mental health issues, and neurological conditions. Furthermore, the disparity in life expectancy between the wealthiest and poorest segments of these countries has expanded over recent years, highlighting the issue of inequality.

The researchers aimed to explore differences in lifespan among six affluent English-speaking countries: Australia, Canada, Ireland, New Zealand, the UK, and the USA, representing some of the most prosperous global economies. They utilised national life tables from the Human Mortality Database and detailed mortality data by age, sex, and cause from the World Health Organization Mortality Database to assess these disparities.

The study’s key findings reveal that Australia consistently outperformed its peers in terms of life expectancy at birth from the early 1990s onwards. Australian women led by 1.26 to 3.95 years and men by 0.97 to 4.88 years as of 2018. Notably, Australia had a significant 4 to 5 year life expectancy advantage over the USA and a 1 to 2.5 year advantage over the other mentioned countries.

Canada generally held the second-highest life expectancy throughout the observed period, recently matched by Ireland and New Zealand. However, the USA consistently lagged, recording the lowest life expectancy every year since 2001, and the UK frequently occupied the second lowest position in the most recent decade. The disparities in life expectancy at birth between the best and worst-performing countries have widened over time, with the gaps doubling for men and increasing by 30% for women between Australia and the USA from 1990 to 2019.

The research highlighted that Australians benefit from lower death rates across nearly all age groups, particularly between ages 45 and 84. Critical health issues contributing to life expectancy differences in this age range include ischaemic heart disease, other circulatory diseases, cancers, respiratory diseases, and neurological conditions, predominantly Alzheimer’s disease and related dementias. Additionally, Australia shows lower mortality from external causes like drugs, alcohol, and certain cancers.

Regarding regional differences within countries, the study found the lowest life expectancy in certain US states. In contrast, all regions in the UK and Ireland surpassed life expectancy thresholds of 81 years for women and 76.5 years for men. Australia exhibited the least within-country inequality in life expectancy, particularly noticeable after age 40, with Canada following. In contrast, inequality among both sexes was most pronounced in New Zealand, Ireland, and the USA.

While acknowledging limitations such as potential inconsistencies in the cause-of-death coding at older ages, the researchers suggest several factors for Australia’s superior performance, including a high proportion of overseas-born residents and robust public health policies on issues like smoking, gun ownership, and mental health. Despite its leading position, Australia faces challenges in reducing health disparities, especially among its indigenous populations and in combating obesity.

The study concludes by positing that Australia could serve as a model for other English-speaking countries, particularly those performing less well like the USA and UK, to improve both lifespans and reduce inequalities in life expectancy.

More information: Rachel Z Wilkie et al, Life expectancy and geographic variation in mortality: an observational comparison study of six high-income Anglophone countries, BMJ Open. DOI: 10.1136/bmjopen-2023-079365

Journal information: BMJ Open Provided by BMJ Group

Recent Studies Show Promise for Enhancing the Efficacy of Widely Used Diabetes and Weight-Loss Medications

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Recent findings from the University of Michigan suggest that a network of proteins within the central nervous system could enhance the efficacy and mitigate side effects of common diabetes and weight-loss medications. They were published today in the Journal of Clinical Investigation; the research centres on two proteins, melanocortin three and melanocortin 4, located predominantly on the surface of brain neurons. These proteins are crucial in regulating feeding behaviours and maintaining energy balance in the body.

Roger Cone, a U-M physiologist who spearheaded the research, explained that melanocortin three and melanocortin 4 influence a range of functions, from monitoring long-term energy reserves to interpreting signals from the gut about short-term fullness or satiety. The study mainly looks at GLP-1 agonists—such as semaglutides and tirzepatides—renowned for their effectiveness against not only type 2 diabetes but also obesity, heart disease, and potentially addiction. These drugs operate by emulating a natural hormone produced by the gut when complete, which then prompts the brain to curb feeding behaviour.

Cone posed a critical question: “How do GLP-1 drugs, which modulate satiety signals, perform when we prime the melanocortin system?” To explore this, his team conducted experiments using mouse models, comparing the effects of various hormones that decrease food intake. They tested these hormones in typical mice, in those lacking the MC3R protein genetically, in mice treated with chemicals that inhibit MC3R, and in those administered a drug that enhances MC4R activity. Since MC3R naturally curtails MC4R activity, blocking MC3R while boosting MC4R has comparable outcomes.

The study, led by first author Naima Dahir, a postdoctoral research fellow in Cone’s lab, discovered that either inhibiting MC3R or boosting MC4R activity heightened the mice’s sensitivity to GLP-1 drugs and other hormones impacting feeding behaviour. Mice treated with a combination of a GLP-1 drug and either an MC4R agonist or an MC3R antagonist experienced up to a fivefold increase in weight loss and reduced feeding compared to those treated solely with GLP-1 drugs.

“Our findings reveal that activating the central melanocortin system significantly increases the response to not just GLP-1s, but to all anti-feeding hormones we tested,” noted Cone. The research team also monitored brain activity associated with nausea—a common side effect of GLP-1 drugs—and found no increase in such activity when GLP-1 drugs were used alongside modifications to the melanocortin system. In contrast, we stimulated melanocortin neurons, which markedly enhanced the GLP-1 drug-induced activation of neurons in brain areas responsible for feeding.

These results suggest that combining existing GLP-1 drugs with an MC4R agonist could amplify the drugs’ desired effects fivefold without exacerbating unwanted side effects. This approach could allow patients who are particularly sensitive to side effects to use lower doses or enhance outcomes for patients who are unresponsive to current drug dosages. However, further drug development and clinical trials are necessary before such treatments can be implemented.

Although the research was conducted in mouse models, Cone remains optimistic about its applicability to humans. “The melanocortin system is highly conserved in humans,” he remarked. “Based on our decades of research into these proteins, which has shown consistent results between mice and humans, I believe these findings will likely be transferable to clinical settings.”

More information: Naima S. Dahir et al, Subthreshold activation of the melanocortin system causes generalized sensitization to anorectic agents in mice, Journal of Clinical Investigation. DOI: 10.1172/JCI178250

Journal information: Journal of Clinical Investigation Provided by University of Michigan

Ageing and Dementia-Related Memory Decline: The Predictive Role of Dendritic Spine Head Diameter in Elderly Memory Retention

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Memory declines with age, often marked by a diminished ability to recall personal experiences. Traditionally associated with the degeneration of dendritic spines—critical elements of synaptic connections in the brain—this process has been reevaluated in light of new research. A study published in Science Advances, conducted by teams from the University of Alabama at Birmingham and Rush University Medical Center in Chicago, proposes that retaining memories from past experiences depends more on the quality rather than the quantity of synaptic connections in older people.

Jeremy Herskowitz, Ph.D., associate professor in the Department of Neurology at UAB and corresponding author of the study, characterizes the findings as a significant departure from established beliefs. For decades, the dominant theory posited that memory decline was primarily due to the loss of dendritic spines, indicating synaptic deterioration. This study reveals that, although synapses diminish with age—a process considered normal from ages 40 to 85—the remaining synapses can compensate for this loss, challenging the previous understanding of memory decline’s mechanics.

The implications of this discovery are particularly promising for the elderly population. Herskowitz explains that the study demonstrates an enduring synaptic plasticity in older individuals, which can still effectively support memory retention. This insight suggests that therapies aimed at remodelling dendritic spines and synapses could significantly enhance memory preservation and cognitive function in ageing individuals or those suffering from memory impairments associated with Alzheimer’s disease.

The Religious Orders Study and the Rush Memory and Aging Project (ROSMAP) at Rush University provided the foundation for this research. This project enrols Catholic nuns, priests, and brothers over the age of 65 who are free from known dementia at enrollment and agree to donate their brains for research post-mortem. The study examined brain samples from 128 ROSMAP participants, with an average age of 90.5 years at death, who had undergone annual cognitive testing covering multiple domains.

In their analysis, Herskowitz and his team stained and photographed thin slices of brain tissue, constructing three-dimensional digital reconstructions of 55,521 dendritic spines across 2,157 neurons. They utilized innovative statistical and machine learning techniques to assess correlations between various spine morphology measurements and multiple indicators of brain function, age, and Alzheimer’s disease pathology. Their findings highlighted that larger dendritic spine head diameters in the temporal cortex were associated with better episodic memory performance, underscoring the importance of synaptic strength over quantity in memory preservation in old age.

This research, which spanned over two and a half years and continued through the COVID-19 pandemic under strict conditions, opens new pathways for therapeutic interventions focusing on enhancing synaptic strength and spine head diameter. These approaches could potentially offer more significant benefits for older adults, particularly those in the preclinical phases of Alzheimer’s disease, emphasizing the fundamental role of synapses in brain function and the dynamic process of synaptic formation and elimination as part of brain plasticity.

More information: Courtney K. Walker et al, Dendritic spine head diameter predicts episodic memory performance in older adults, Science Advances. DOI: 10.1126/sciadv.adn5181

Journal information: Science Advances Provided by University of Alabama at Birmingham

Consuming More Fruits and Vegetables to Decrease Dietary Acidity Reduces Blood Pressure and Enhances Cardiac and Renal Health in Hypertensive Patients

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Physicians strongly recommend that fruits and vegetables be integral to treating hypertension. Studies confirm that diets rich in these natural foods lower blood pressure, reduce cardiovascular risks, and bolster kidney health due to their alkaline effects. These findings, outlined in a five-year randomized control trial published in The American Journal of Medicine by Elsevier, highlight the significant benefits of such dietary adjustments. Despite the advancements in pharmacological treatments for hypertension, the incidence of chronic kidney disease related to hypertension and its associated cardiovascular mortality continues to climb, with heart disease remaining the leading cause of death among these patients.

The Dietary Approaches to Stop Hypertension (DASH) diet emphasizes a high intake of fruits and vegetables. It has been shown to effectively lower blood pressure, marking it as the preferred initial treatment for primary hypertension. However, despite solid epidemiological evidence supporting it, the DASH diet is often under-prescribed and needs to be fully implemented. This diet, alongside others high in fruits and vegetables, is linked to various health benefits, including lower blood pressure, decreased chronic kidney disease progression, reduced cardiovascular risk, and decreased mortality from heart diseases.

Dr. Donald E. Wesson, MD, MBA, from the Department of Internal Medicine at Dell Medical School at The University of Texas at Austin and the study’s lead investigator, explains that his work on how kidneys manage blood acidity has been crucial in understanding dietary impacts on kidney and heart health. His team’s animal and patient studies have shown that diets high in animal products harm kidney health by forcing the kidneys to remove more acid from the blood, leading to injury. Conversely, a diet rich in fruits and vegetables, which lowers dietary acid, benefits kidney and heart health.

The recent study involved hypertensive patients without diabetes who had high levels of urine albumin excretion, a sign of severe kidney disease and an increased risk of worsening conditions and cardiovascular issues. The 153 participants were divided into three groups: one added 2-4 cups of alkaline-producing fruits and vegetables to their daily diet, another received sodium bicarbonate tablets, and a control group continued with standard medical care. The results showed that while the fruits and vegetables and the sodium bicarbonate improved kidney health, only the fruits and vegetables group saw reductions in blood pressure and improved cardiovascular risk indices.

Dr Maninder Kahlon, PhD, co-investigator from the Department of Population Health, highlights that the benefits of fruits and vegetables extend beyond kidney health to include significant reductions in blood pressure and cardiovascular risks, which were not observed with sodium bicarbonate. This underlines the necessity of prioritizing fruits and vegetables in hypertension treatment, allowing for lower doses of medications while achieving comprehensive health improvements.

The research team advocates for a shift in treatment paradigms, suggesting that dietary interventions, especially those rich in fruits and vegetables, should be the starting point for managing hypertension rather than secondary options following pharmacological interventions. This approach effectively manages blood pressure and provides protective benefits against kidney and heart diseases. Furthermore, they recommend that hypertensive patients discuss with their doctors the possibility of measuring their urine albumin-to-creatinine ratio (UACR) to check for underlying kidney disease and associated cardiovascular risks, reinforcing the importance of preventive health measures in managing hypertension.

More information: Nimrit Goraya et al, Kidney and Cardiovascular Protection Using Dietary Acid Reduction in Primary Hypertension: A Five-Year, Interventional, Randomized, Control Trial, The American Journal of Medicine. DOI: 10.1016/j.amjmed.2024.06.006

Journal information: The American Journal of Medicine Provided by Elsevier