Category: Ageing

Categories : Ageing Neurodegenerative DiseasesTags :

Could Bizarre Visual Symptoms Be a Telltale Sign of Alzheimer’s?

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A team of international researchers, led by UC San Francisco, has completed the first large-scale study of posterior cortical atrophy, a baffling constellation of visuospatial symptoms that present as the first signs of Alzheimer’s disease. These symptoms occur in up to 10% of cases of Alzheimer’s disease.

The study, which appears in The Lancet Neurology,  includes data from more than 1000 patients at 36 sites in 16 countries.

Posterior cortical atrophy (PCA) overwhelmingly predicts Alzheimer’s, the researchers found. Some 94% of the PCA patients had Alzheimer’s pathology and the remaining 6% had conditions like Lewy body disease and frontotemporal lobar degeneration. In contrast, other studies show that 70% of patients with memory loss have Alzheimer’s pathology.

Unlike memory issues, patients with PCA struggle with judging distances, distinguishing between moving and stationary objects and completing tasks like writing and retrieving a dropped item despite a normal eye exam, said co-first author Marianne Chapleau, PhD, of the UCSF Department of Neurology, the Memory and Aging Center and the Weill Institute for Neurosciences.

Most patients with PCA have normal cognition early on, but by the time of their first diagnostic visit, an average 3.8 years after symptom onset, mild or moderate dementia was apparent with deficits identified in memory, executive function, behaviour, and speech and language, according to the researchers’ findings.

At the time of diagnosis, 61% demonstrated “constructional dyspraxia,” an inability to copy or construct basic diagrams or figures; 49% had a “space perception deficit,” difficulties identifying the location of something they saw; and 48% had “simultanagnosia,” an inability to visually perceive more than one object at a time. Additionally, 47% faced new challenges with basic math calculations and 43% with reading.

We need better tools and training to identify patients

“We need more awareness of PCA so that it can be flagged by clinicians,” said Chapleau. “Most patients see their optometrist when they start experiencing visual symptoms and may be referred to an ophthalmologist who may also fail to recognise PCA,” she said. “We need better tools in clinical settings to identify these patients early on and get them treatment.”

The average age of symptom onset of PCA is 59, several years younger than the typical memory symptoms of Alzheimer’s. This is another reason why patients with PCA are less likely to be diagnosed, Chapleau added.

Early identification of PCA may have important implications for Alzheimer’s treatment, said co-first author Renaud La Joie, PhD, also of the UCSF Department of Neurology and the Memory and Aging Center. In the study, levels of amyloid and tau, identified in cerebrospinal fluid and imaging, as well as autopsy data, matched those found in typical Alzheimer’s cases. As a result, patients with PCA may be candidates for anti-amyloid therapies, like lecanemab (Leqembi), approved by the U.S Food and Drug Administration in January 2023, and anti-tau therapies, currently in clinical trials, both of which are believed to be more effective in the earliest phases of the disease, he said.

“Patients with PCA have more tau pathology in the posterior parts of the brain, involved in the processing of visuospatial information, compared to those with other presentations of Alzheimer’s. This might make them better suited to anti-tau therapies,” he said.

Patients have mostly been excluded from trials, since they are “usually aimed at patients with amnestic Alzheimer’s with low scores on memory tests,” La Joie added. “However, at UCSF we are considering treatments for patients with PCA and other non-amnestic variants.”

Better understanding of PCA is “crucial for advancing both patient care and for understanding the processes that drive Alzheimer’s disease,” said senior author Gil Rabinovici, MD, director of the UCSF Alzheimer’s Disease Research Center. “It’s critical that doctors learn to recognise the syndrome so patients can receive the correct diagnosis, counseling and care.

“From a scientific point of view, we really need to understand why Alzheimer’s is specifically targeting visual rather than memory areas of the brain. Our study found that 60% of patients with PCA were women – better understanding of why they appear to be more susceptible is one important area of future research.”

Source: University of California San Francisco

Categories : Ageing Diet and NutritionTags :

Meat Builds Muscle Proteins Better than Equivalent Vegan Dishes

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Older adults require more protein but eat less than younger people, making it a challenge for them to maintain muscle mass. Eating a meal with meat ensures that muscle proteins are built faster than a vegan meal with the same amount of protein. This study, published in The Journal of Nutrition, was the first to compare the speed at which muscle proteins are being made after eating a complete meal with animal or plant proteins.

Every two to three months the proteins in human muscle are completely renewed. In order to make muscle proteins, we need protein from food, for example from animal sources such as meat, cheese and yoghurt, or from plant products such as beans, nuts and soymilk. Previous research on protein powders showed that animal proteins have better muscle-building properties than plant proteins. “But in reality, we do not get our proteins in powder form, but through complete meals,” says study author and PhD student Philippe Pinckaers. “Those meals contain different types of protein and other nutrients such as fibres, fats and carbohydrates. These nutrients affect how proteins are released from the diet and influences the making of muscle proteins.”

To investigate how muscles respond after eating a complete meal, Pinckaers asked 16 participants aged over 65 to come to the lab twice for a dinner meal.

Dining out in the lab

On one day, the participants sat down to a meal with quinoa with chickpeas, broad beans, soy beans and soy sauce was on the menu, while on the other day the menu consisted of a beef tartlet, potatoes, green beans, apple sauce and herb butter. Both meals had similar amounts of protein, fat, carbohydrates and calories. Prior to the meals, participants were administered an infusion of special amino acids.

“The amino acids administered via the infusion were marked, as it were with a flag,” Pinckaers explains. “We took small pieces of muscle tissue from the participants and were able to measure the amount of ‘flags’ in them. If more flags are measured, it means that muscle proteins are built up faster, which is beneficial for muscles. In this way, we found that after eating a meal with animal protein, muscle protein was built up faster than after eating a vegan meal. This means that a vegan meal does not have the same capacity to make muscle proteins as a meal that includes animal proteins.” This difference arises partly because plant-based foods are harder to digest, and because they naturally contain fewer essential amino acids.

Context is key  

The results do not mean that everyone should eat meat or other animal products, clarifies professor of exercise science and lead researcher Luc van Loon. “Healthy people can very well compensate for the lower quality of plant proteins by eating more of them.” For elderly or frail patients it is a bit more complicated. “Elderly people actually need more protein in order to reach the same level of muscle protein synthesis, when compared to young individuals. However, they actually eat less. Also, patients with reduced appetite or who do not exercise much, for example during hospitalisation, may have trouble consuming a sufficient amount of protein. For them, it is therefore important to choose protein sources that stimulate the making of muscle proteins as much as possible. The best sources in this situation would be proteins from animal products.”

Source: Maastricht University

Categories : Ageing Diet and NutritionTags :

How Calorie Restriction Slows Aging in the Brain

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Restricting calories is known to improve health and increase lifespan, but much of how it does so remains a mystery, especially in regard to how it protects the brain. Now, scientists from the Buck Institute for Research on Aging have uncovered a role for a gene called OXR1 that is necessary for the lifespan extension seen with dietary restriction and is essential for healthy brain aging.

“When people restrict the amount of food that they eat, they typically think it might affect their digestive tract or fat buildup, but not necessarily about how it affects the brain,” said Kenneth Wilson, PhD, Buck postdoc and first author of the study, published in Nature Communications. “As it turns out, this is a gene that is important in the brain.”

The team additionally demonstrated a detailed cellular mechanism of how dietary restriction can delay aging and slow the progression of neurodegenerative diseases. The work, done in fruit flies and human cells, also identifies potential therapeutic targets to slow aging and age-related neurodegenerative diseases.

“We found a neuron-specific response that mediates the neuroprotection of dietary restriction,” said Buck Professor Pankaj Kapahi , PhD, co-senior author of the study. “Strategies such as intermittent fasting or caloric restriction, which limit nutrients, may enhance levels of this gene to mediate its protective effects.”

“The gene is an important brain resilience factor protecting against aging and neurological diseases,” said Buck Professor Lisa Ellerby, PhD, co-senior author of the study.

Understanding variability in response to dietary restriction

Members of the team have previously shown mechanisms that improve lifespan and healthspan with dietary restriction, but it was not clear why there is so much variability in response to reduced calories across individuals and different tissues. This project was started to understand why different people respond to diets in different ways.

The team began by scanning about 200 strains of flies with different genetic backgrounds. The flies were raised with two different diets, either with a normal diet or with dietary restriction, which was only 10% of normal nutrition. Researchers identified five genes which had specific variants that significantly affected longevity under dietary restriction. Of those, two had counterparts in human genetics.

The team chose one gene to explore thoroughly, called “mustard” (mtd) in fruit flies and “Oxidation Resistance 1” (OXR1) in humans and mice. The gene protects cells from oxidative damage, but the mechanism for how this gene functions was unclear. The loss of OXR1 in humans results in severe neurological defects and premature death. In mice, extra OXR1 improves survival in a model of amyotrophic lateral sclerosis (ALS).

The link between brain aging, neurodegeneration and lifespan

To figure out how a gene that is active in neurons affects overall lifespan, the team did a series of in-depth tests. They found that OXR1 affects a complex called the retromer, which is a set of proteins necessary for recycling cellular proteins and lipids. “The retromer is an important mechanism in neurons because it determines the fate of all proteins that are brought into the cell,” said Wilson. Retromer dysfunction has been associated with age-related neurodegenerative diseases that are protected by dietary restriction, specifically Alzheimer’s and Parkinson’s diseases.

Overall, their results told the story of how dietary restriction slows brain aging by the action of mtd/OXR1 in maintaining the retromer. “This work shows that the retromer pathway, which is involved in reusing cellular proteins, has a key role in protecting neurons when nutrients are limited,” said Kapahi. The team found that mtd/OXR1 preserves retromer function and is necessary for neuronal function, healthy brain aging, and lifespan extension seen with dietary restriction.

“Diet is influencing this gene. By eating less, you are actually enhancing this mechanism of proteins being sorted properly in your cells, because your cells are enhancing the expression of OXR1,” said Wilson.

The team also found that boosting mtd in flies caused them to live longer, leading researchers to speculate that in humans excess expression of OXR1 might help extend lifespan. “Our next step is to identify specific compounds that increase the levels of OXR1 during aging to delay brain aging,” said Ellerby.

“Hopefully from this we can get more of an idea of why our brains degenerate in the first place,” said Wilson.

“Diet impacts all the processes in your body,” he said. “I think this work supports efforts to follow a healthy diet, because what you eat is going to affect more than you know.”

Source: Buck Institute for Research on Aging

Categories : Ageing Regenerative MedicineTags :

Restoring Muscle Strength Lost to Aging or Injury

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A small molecule previously shown to enhance strength in injured or old laboratory mice does so by restoring lost connections between nerves and muscle fibres, Stanford Medicine researchers have found.

The molecule blocks the activity of an aging-associated enzyme, or gerozyme, called 15-PGDH that naturally increases in muscles as they age. The study, which was published in Science Translational Medicine, showed that levels of the gerozyme increase in muscles after nerve damage and that it is prevalent in muscle fibres of people with neuromuscular diseases.

The research is the first to show that damaged motor neurons can be induced to regenerate in response to a drug treatment and that lost strength and muscle mass can be at least partially regained. It suggests that, if similar results are seen in humans, the drug may one day be used to prevent muscle loss of muscle strength due to aging or disease or to hasten recovery from injury.

It’s estimated that sarcopenia, or debilitating muscle frailty, affects about 30% of people over 80 and costs the United States around $380 billion each year.

“There is an urgent, unmet need for drug treatments that can increase muscle strength due to aging, injury or disease,” said Helen Blau, PhD, professor of microbiology and immunology. “This is the first time a drug treatment has been shown to affect both muscle fibres and the motor neurons that stimulate them to contract in order to speed healing and restore strength and muscle mass. It’s unique.”

Blau, the Donald E. and Delia B. Baxter Foundation Professor and director of the Baxter Laboratory for Stem Cell Biology, is the senior author of the study. Postdoctoral scholar Mohsen Bakooshli, PhD, and former postdoctoral scholar Yu Xin Wang, PhD, are the lead authors of the study. Wang is now an assistant professor at the Sanford Burnham Prebys Medical Discovery Institute in San Diego.

Addressing loss of strength

The finding is the latest from the Blau laboratory focused on understanding how muscles weaken from aging or disease, and whether it’s possible to combat this decline. In 2021, the group showed that blocking the activity of 15-PGDH in 24-month-old laboratory mice significantly enhances the animals’ leg strength and endurance when running on a treadmill. (Laboratory mice typically live about 26 to 30 months.) But it wasn’t clear exactly how.

The new research shows that the effect is due to the restoration of lost connections between the nerves and the muscle. These connections, called neuromuscular junctions, are how the brain signals muscles to contract. In aging, some of these connections are lost, causing muscle contractions to become less powerful and muscles to atrophy. People typically lose muscle mass and strength, up to 10% per decade, after the age of 50.

Conditions other than aging can also destabilise these connections, including the disuse of muscles due to bedrest after illness or injury, or muscle-wasting diseases like spinal muscular atrophy or amyotrophic lateral sclerosis (also known as ALS).

Blau’s previous research showed that a molecule called PGE2 is critical to the function of stem cells in muscle fibres that repair damage – including the microtears from exercise that lead to an increase in muscle mass and strength. They subsequently showed that levels of 15-PGDH, which breaks down PGE2, increase in the muscles with age and that the loss of strength with aging could be overcome by inhibiting the activity of this PGE2-degrading enzyme.

“PGE2 is part of the body’s natural healing mechanism, and its levels increase in muscle after injury,” Blau said. “We wanted to learn how age triggers an increase in 15-PGDH, and therefore the degradation and loss of PGE2.”

A lack of nerves

The researchers knew that muscles become less innervated, or infiltrated with nerves, as people and animals age. They wondered if that loss could be what triggers the rising levels of 15-PGDH.

“We found that when you cut the nerve that innervates the leg muscles of mice, the amount of 15-PGDH in the muscle increases rapidly and dramatically,” Blau said. “This was an exciting new insight. But what surprised us most was that when these mice are treated with a drug that inhibits 15-PGDH activity, the nerve grows back and makes contact with the muscle more quickly than in control animals, and that this leads to a faster recovery of strength and function.”

Additional experiments showed that treatment with the drug restored neuromuscular junctions lost during aging and increased muscle strength and function in old laboratory mice. The researchers also identified discrete clumps of 15-PGDH in the muscle fibres of people with several types of neuromuscular disorders suggesting that the gerozyme may have a role in causing these human disorders.

Blau and her colleagues plan to investigate at a molecular level how neural growth is stimulated by blocking 15-PGDH activity. Blau has also co-founded a company, Epirium Bio, to develop similar drugs for use in humans. Although her lab is still conducting animal studies, the company hopes to launch a clinical trial within the next year or so.

“Our next steps will be to examine whether blocking 15-PGDH function in people with spinal muscular atrophy can increase lost muscle strength in combination with gene therapy or other treatments,” Blau said. “We are also looking at ALS to see if something like this might help these patients. It’s really exciting that we are able to affect both muscle function and motor neuron growth.”

Source: Stanford Medicine

Categories : Ageing VaccinesTags :

Why Vaccines don’t Work as Well for Some Older People

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Age-related changes in the immune system also play a role in variable responses to vaccines and overall lower efficacy of vaccines compared to younger adults. Researchers at The Jackson Laboratory (JAX) and UConn Health are investigating why vaccines don’t work as well in some older adults, and have published their insights in Nature.

Protection against pneumococcal infections

Infants and older adults are at greatest risk for pneumococcal infections, and case-fatality rates increase with age for reasons still not well understood. Fortunately, several vaccines developed against the polysaccharides found on the surface of Streptococcus pneumoniae, including PPSV23 (Pneumovax), are generally effective in older adults, though less in younger adults. Conjugating the polysaccharide with a protein, such as a nontoxic variant of a diphtheria toxin, can induce additional adaptive immune activation, resulting in better protection. The strategy was used to develop a new class of FDA-approved conjugated vaccines (eg, PCV13, Prevnar). Despite these advances, responses to pneumococcal vaccines still decline with age. Moreover, it remains unclear which of these two vaccines are preferable in subpopulations of older adults.

To address these gaps in knowledge, a team led by JAX Associate Professor Duygu Ucar, PhD, UConn Health Professor George Kuchel, MD, CM, and Jacques Banchereau, PhD (Immunoledge, Montclair, NJ), compared pre- and post-vaccine immune characteristics. Their findings identify the biological traits underlying variable responses to the two different vaccines. Importantly, they also reveal distinct baseline (ie, pre-vaccination) predictors that have the potential to affect vaccination strategies and lead to interventions that are more effective, by virtue of being more specific.

Efficacy indicators

A cohort of 39 pneumococcal vaccine-naïve healthy adults, all aged 60 or above, received a single dose of PPSV23 or PCV13 from May to early fall. Blood was drawn before vaccination, then one, 10, 28 and 60 days after to provide longitudinal data. Following vaccination, the researchers developed measures to quantify vaccine responses and rank donors with respect to responsiveness within the cohort. While overall responses to both vaccines were comparable, there were clear differences in baseline immune phenotypes, separating the strong and weak responders.

The baseline abundance of two specific T cell types, Th1 and Th17 cells, played an important role in PCV13 responses. Th1 cells produce molecular signals to activate early innate immune responses to pathogens, while Th17 cells also contribute to the defence response by producing a different group of inflammatory signalling molecules. For PCV13 vaccine responses, higher levels of Th1 cells showed a positive association and higher levels of Th17 cells a negative association. Thus, a pre-vaccination Th1/ Th17 ratio can be predictive of PCV13 response strength. Interestingly, women have a higher frequency of Th1 and lower frequency of Th1 7 cells compared to men and responded more strongly to the PCV13 vaccine.

From the pre-vaccination gene expression data, the researchers uncovered a gene module that included cytotoxic genes that was associated with reduced PCV13 responses, called the CYTOX signature. Single cell profiling linked this gene expression signature to mature CD16+ Natural Killer (NK) cells. The abundance of mature CD16+ NK cells in blood was associated with responses to PCV13, where weak responders had more CD16+ NK cells than strong responders. The CYTOX signature was not associated with responses to the alternative PPSV23 vaccine, however – another, distinct gene set predicted responses to PPSV23.

“Our study offers a reminder that ‘one size fits all’ approaches do not work well for older patients,” says Kuchel. “Moreover, if our findings can be replicated in other populations, they may offer remarkable opportunities for implementing care models for older adults involving Precision Gerontology that are more effective by virtue of being more precise, ultimately matching individuals with those vaccines that work best for them. Precision Gerontology represents the thematic focus of the UConn Older Americans Independence ‘Pepper’ Center award from NIH.”

Implications for disease prevention

A surprising aspect of the study is that the baseline predictors for the two available classes of pneumococcal vaccines are quite distinct and independent from each other, despite both vaccines using the same bacterial polysaccharides to provoke the protective immune response. Importantly, however, the paper shows that responses to the two vaccines can be predicted in older adults based on specific pre-vaccination characteristics, and the findings imply that individuals can be readily stratified based on which vaccine is likely to work best for them. For example, older adults with low CYTOX/CD16+ NK cell levels will likely respond well to the PCV13 vaccine, while those with high CYTOX would more likely benefit from the PPSV23 vaccine. Overall, the results have important implications for more precise vaccination strategies for pneumococcal vaccines, and potentially for other vaccines as well, to better protect older adults from infection and disease.

Source: University of Connecticut

Categories : Ageing Diseases, Syndromes and ConditionsTags :

Promising Results for Epilepsy Drug in Slowing Osteoarthritis

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Yale researchers report in the journal Nature that they have identified a drug target that may alleviate joint degeneration associated with osteoarthritis.

The most common therapies for the degenerative disease have been pain relievers and lifestyle changes, to reduce pain and stiffness, but there is a pressing need for therapies that can prevent joint breakdown that occurs in osteoarthritis, which occurs as a result of the breakdown of cartilage in the joints.

Sodium channels found in cell membranes produce electrical impulses in “excitable” cells within muscles, the nervous system, and the heart. And in previous research, Yale’s Stephen G. Waxman identified the key role of one particular sodium channel, called Nav1.7, in the transmission of pain signals.

Now, the labs of Chuan-Ju Liu, professor of orthopaedics, and Waxman, professor neurology, neuroscience and pharmacology, have found that the same Nav1.7 channels are also present in non-excitable cells that produce collagen and help maintain the joints in the body. These channels can be targeted by existing drugs to block them.

In the new study, the researchers deleted Nav1.7 genes from these collagen-producing cells and significantly reduced joint damage in two osteoarthritis models in mice.

They also demonstrated that drugs used to block Nav1.7 – including carbamazepine, a sodium channel blocker currently used to treat epilepsy and trigeminal neuralgia – also provided substantial protection from joint damage in the mice.

“The function of sodium channels in non-excitable cells has been a mystery,” Waxman said.

“This new study provides a window on how small numbers of sodium channels can powerfully regulate the behaviour of non-excitable cells.”

“The findings open new avenues for disease-modifying treatments,” added Wenyu Fu, a research scientist in the Liu laboratory and first author of the study.

Source: Yale University

Categories : Ageing NeurologyTags :

Older Adults’ Migraine Diagnosis Linked to Tripled Risk of Vehicle Crash

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A new study from researchers at the University of Colorado Anschutz Medical Campus finds that older adult drivers who are recently diagnosed with migraines are three times as likely to experience a motor vehicle crash. Older adult drivers who reported having ever had migraines in the past were no more likely to have a motor vehicle crash than those without migraines.

The study, published in the Journal of the American Geriatrics Society, also explored the relationships medications commonly prescribed for migraine management have with increased crash risk.

“Migraine headaches affect more than 7% of US adults over the age of 60,” says Carolyn DiGuiseppi, MPH, PhD, MD, professor with the Colorado School of Public Health and study lead author.

“The US population is aging, which means increasing numbers of older adult drivers could see their driving abilities affected by migraine symptoms previously not experienced. These symptoms include sleepiness, decreased concentration, dizziness, debilitating head pain and more.”

Researchers conducted a five-year longitudinal study of more than 2500 active drivers aged 65-79 in five sites across the United States.

Participants were categorised as having previously been diagnosed with migraine symptoms (12.5%), no previous diagnosis but experienced symptoms during the study timeframe (1.3%) or never migraine respondents.

Results indicate those with previous diagnosis did not have a different likelihood of having crashes after baseline, while those with new onset migraines were three times as likely to experience a crash within one year of diagnosis.

Previously diagnosed drivers nevertheless had experienced more hard braking events compared to adults who had never experienced a migraine.

Additionally, researchers examined the role medications commonly prescribed for migraines have in motor vehicle events and found that there was no impact on the relationship between migraines and either crashes or driving habits.

Few participants in the study sample were using acute migraine medications, however.

“These results have potential implications for the safety of older patients that should be addressed,” says DiGuiseppi. “Patients with a new migraine diagnosis would benefit from talking with their clinicians about driving safety, including being extra careful about other risks, such as distracted driving, alcohol, pain medication and other factors that affect driving.”

Source: University of Colorado Anschutz Medical Campus

Categories : Ageing GenderTags :

COVID, Opioid Pandemic Widen Gender Gap in Life Expectancy in the US

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Women have long been known to outlive men. But new research published in JAMA Internal Medicine shows that, at least in the United States, the gap has been widening for more than a decade. Among the factors driving the trend are the COVID pandemic and the opioid overdose epidemic.

The study, led by UC San Francisco and Harvard T.H. Chan School of Public Health, found the difference between how long American men and women live increased to 5.8 years in 2021, the largest since 1996. This is an increase from 4.8 years in 2010, when the gap was at its smallest in recent history.

The pandemic, which took a disproportionate toll on men, was the biggest contributor to the widening gap from 2019–2021, followed by unintentional injuries and poisonings (mostly drug overdoses), accidents and suicide.

“There’s been a lot of research into the decline in life expectancy in recent years, but no one has systematically analysed why the gap between men and women has been widening since 2010,” said the paper’s first author, Brandon Yan, MD, MPH, a UCSF internal medicine resident physician and research collaborator at Harvard Chan School.

Life expectancy in the US dropped in 2021 to 76.1 years, falling from 78.8 years in 2019 and 77 years in 2020.

The shortening lifespan of Americans has been attributed in part to so-called “deaths of despair.” The term refers to the increase in deaths from such causes as suicide, drug use disorders and alcoholic liver disease, which are often connected with economic hardship, depression and stress.

“While rates of death from drug overdose and homicide have climbed for both men and women, it is clear that men constitute an increasingly disproportionate share of these deaths,” Yan said.

Interventions to reverse a deadly trend

Using data from the National Center for Health Statistics, Yan and fellow researchers from around the country identified the causes of death that were lowering life expectancy the most. Then they estimated the effects on men and women to see how much different causes were contributing to the gap.

Prior to the COVID pandemic, the largest contributors were unintentional injuries, diabetes, suicide, homicide and heart disease.

But during the pandemic, men were more likely to die of the virus. That was likely due to a number of reasons, including differences in health behaviours, as well as social factors, such as the risk of exposure at work, reluctance to seek medical care, incarceration and housing instability. Chronic metabolic disorders, mental illness and gun violence also contributed.

Yan said the results raise questions about whether more specialised care for men, such as in mental health, should be developed to address the growing disparity in life expectancy.

“We have brought insights to a worrisome trend,” Yan said. “Future research ought to help focus public health interventions towards helping reverse this decline in life expectancy.”

Yan and co-authors, including senior author Howard Koh, MD, MPH, professor of the practice of public health leadership at Harvard Chan School, also noted that further analysis is needed to see if these trends change after 2021.

“We need to track these trends closely as the pandemic recedes,” Koh said. “And we must make significant investments in prevention and care to ensure that this widening disparity, among many others, do not become entrenched.”

Source: University of California – San Francisco

Categories : Ageing Immune SystemTags :

New Approach May Take the Guesswork out of Selecting Treatments for RA

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New research reported in the journal Nature could lead to new targeted treatments for rheumatoid arthritis (RA). The findings showed that guesswork could be taken out of selecting treatments for each patient, and this might one day also be extended to other autoimmune conditions.

The study was led by University of Colorado School of Medicine faculty members Fan Zhang, PhD, and Anna Helena Jonsson, MD, PhD. The Accelerating Medicines Partnership: Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP: RA/SLE) Network collected inflamed tissue from 70 patients with RA from across the country and the United Kingdom. Jonsson supervised the team of scientists who processed these samples for analysis, and Zhang led the computation analysis of the data. These efforts yielded a cell atlas encompassing more than 300 000 cells from synovial tissue. Further analysis revealed that there are six different subgroups of RA based on their cellular makeup.

“We hope the data will help us discover new treatment targets,” says Jonsson, assistant professor of rheumatology. “We wanted to make it public so that researchers across the country and across the world can continue working on new treatment ideas for rheumatoid arthritis going forward.”

No more guess-and-check

Jonsson, a practicing rheumatologist as well as a researcher, knows that RA patients respond differently to different treatments. Until now, she says, rheumatologists used a “guess and check” method to find a treatment that works for an individual patient.

With the new data and powerful computational classification methods developed by Zhang and the computational analysis team, the researchers were able to quantitatively classify RA types into what they call ‘cell-type abundance phenotypes’, or CTAPs. Developed methods, together with the new cell atlas, can start to identify which patients will respond to which treatments.

“Even when you classify rheumatoid arthritis inflammation using these simple markers – T cell markers, B cells, macrophages and other myeloid cells, fibroblasts, endothelial cells – what we found is that each of those categories is associated with very specific kinds of pathogenic cell types we’ve already discovered,” Jonsson says. “Previous rheumatoid arthritis research found that T cell populations called peripheral helper T cells are relevant in rheumatoid arthritis, as are B cells called antibody-producing B cells, and other specific cell types. What we found is that they’re usually not found all together.

“For example, the peripheral helper cells are found with the B cells in only one category of RA, and the pathogenic macrophage populations tend to exist in a different category. Because of this, we can start asking questions about how these specific partners work together.”

Source: University of Colorado Anschutz Medical Campus

Categories : AgeingTags :

Cat-borne Toxoplasma Gondii Linked to Frailty in the Elderly

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Toxoplasma gondii, a common, cat-borne parasite already associated with risk-taking behaviour and mental illness in humans may also contribute to exhaustion, loss of muscle mass, and other signs of frailty in older adults, suggests a study published in the Journal of Gerontology: Medical Science.

The research, by an international team of scientists including University of Colorado Boulder, University of Maryland School of Medicine and the University of A Coruña in Spain, is the latest to explore how the tiny, single-celled organism T. gondii could have big impacts on human health.

“We often think of T. gondii infection as relatively asymptomatic, but this study highlights that for some people it may have significant health consequences later on,” said co-author Christopher Lowry, a professor at CU Boulder.

Some 11%–15% of people in the US have been infected with T. gondii at some point and rates tend to be far higher in older individuals. In some countries, more than 65% have been infected. Once infected, people can unknowingly harbour the parasite for life.

For the study, the team examined the blood of 601 Spanish and Portuguese adults over 65, along with measures of a common geriatric syndrome known as frailty – which includes unintentional weight loss, tiredeness, loss of cognitive sharpness and other indications of declining health.

A whopping 67% of study subjects were “seropositive” showing markers in their blood of a latent infection.

The researchers did not, as they originally hypothesized, find an association between any infection to T. gondii and frailty. But they did find that, among those infected, those with higher “serointensity” or a higher concentration of antibodies to the parasite, were significantly more likely to be frail.

Higher serointensity could reflect a more virulent or widespread infection, multiple infections or recent reactivation of a latent infection, the authors said.

“This paper is important because it provides, for the first time, evidence of the existence of a link between frailty in older adults and intensity of the response to T. gondii infection,” said co-author Blanca Laffon, a professor of psychobiology at the Interdisciplinary Centre of Chemistry and Biology at University of A Coruña.

How cats spread T. gondii

Wild and domestic felines are considered the definitive host of the parasite, while warm-blooded animals like birds and rodents serve as secondary hosts: When cats eat infected animals, T. gondii takes up residence and multiplies in their intestines, shedding eggs in their faeces.

People are typically infected via exposure to those eggs (via litter boxes, contaminated water or dirty vegetables) or by eating undercooked pork, lamb or other meat that’s infested.

Most people never know they’ve been infected, with only about 10% initially having brief flu-like symptoms. But T. gondii tends to linger dormant for decades, cloaked in cysts in muscle and brain tissue (specifically the emotion-processing region known as the amygdala) with some insidious impacts, mounting research suggests.

In a creepy evolutionary trick seemingly designed to benefit the parasite’s favourite host, rodents infected with T. gondii tend to lose their fear of felines, making it easier for cats to catch rats and mice. In the wild, infected chimpanzees have been shown to actually grow attracted to the smell of the urine of their feline predator, the leopard.

People who have been infected also tend to engage in risky behaviour, with research showing they tend to be more impulsive, more entrepreneurial and more likely to get in a car accident. They also have higher rates of schizophrenia, certain mood disorders, cognitive problems and are more likely to attempt suicide, according to research by Lowry and Dr Teodor Postolache, a professor in the Department of Psychiatry at University of Maryland School of Medicine and senior author on the new study.

A declining immune response?

The authors caution that the new study does not prove causation, but suggests the association should be researched.

They found that frail people with high T. gondii seropositivity also had higher levels of certain inflammatory markers, suggesting that infection with the parasite could exacerbate inflammation that already occurs with aging – aka. “inflammaging.”

Because latent T. gondii tends to hide out in muscle tissue, Postolache suspects it could also play a role in hastening sarcopenia.

Lowry’s research focuses on the impact microorganisms have on the immune system and, thus, mental health. He notes that many microbes that humans have evolved with impact health in a positive way – a theory known as the ‘Old Friends’ hypothesis. Even T. gondii may have health benefits we aren’t yet aware of, he said. But in some cases, a switch flips, and friends become enemies.

In the case of T. gondii, certain medications or immune compromising diseases like HIV or cancer can enable a latent infection to escape suppression and reactivate, with adverse effects. Even in people with healthy immune systems, Lowry notes, immune function can decline with age, potentially wakening dormant dormant T. gondii.

The researchers hope their study will inspire more research into the relationship between T. gondii and frailty, and ultimately lead to new ways of keeping the parasite from doing harm.

For now, they encourage people – especially pregnant and immunocompromised people – to take steps to avoid infection.

Tips for preventing infection:

Change litter box daily, and wash hands afterward.

Avoid eating undercooked meat.

Rinse fruits and vegetables.

If pregnant or immunocompromised:

Avoid changing the litter box if possible (T. gondii infection during pregnancy can cause serious problems to a developing foetus).

Keep cats indoors.

Avoid stray cats.

Source: University of Colorado at Boulder