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Senescent brain cells may contribute to Alzheimer’s disease

People with Alzheimer’s have more senescent brain cells than those without this disease, a new study shows.
Senescent cells, which are damaged cells in the body that do not die off when they should, have been linked to many aspects of ageing and disease.
The new results, published in Nature Aging, show that these neurons have high levels of tau, a protein that forms tangles in the brains of people with Alzheimer’s.
The study was led by researchers at NIA-supported Alzheimer’s Disease Research Centers at the Wake Forest University School of Medicine and the University of Texas Health Science Center at San Antonio.
Senescent cells
Every day, damaged cells die off and are replaced by new, healthy cells. As people age, the body may not remove damaged cells as efficiently as it used to, and although these cells stop dividing, they do not die off.
These damaged cells that linger, called senescent cells, can release chemicals that harm the healthy cells around them.
But not all senescent cells are destructive, rather, some are also involved in several normal processes in the body.
Many scientists are studying senescent cells further to better understand how they affect health.
Studies using animal models have shown that senescent cells play a role in neurodegeneration and cognitive decline.
It is challenging to study the role of these cells in these age-related brain changes in humans because senescent cells are much fewer in number than healthy cells, are often scattered throughout an organ or tissue, and do not all express the same genes.
For this new study, the scientific team developed a novel approach that combines molecular biology and advanced statistical methods to identify and analyse senescent cells in the donated brains of people who died with Alzheimer’s.
The study
Researchers analysed about 140,000 brain cells taken from 76 autopsied brain samples of people who had Alzheimer’s.
The scientists compared these samples with autopsied samples from people without the disease.
To identify senescent cells, the researchers measured the levels of RNA from three groups of genes involved in processes that are hallmarks of senescence, including inflammation, a halt in cell division, and the body’s response to stress.
Measuring these RNA levels provided estimates of the amounts of multiple proteins linked to senescence in individual cells.
The researchers found that about two per cent of the cells in brain samples from people who had Alzheimer’s were senescent.
Almost all these cells were neurons, which are specialised brain cells that process and transmit messages between different parts of the brain, and from the brain to the muscles and organs of the body.
The senescent neurons had high levels of neurofibrillary tangles, which build up when an abnormal form of the tau protein accumulates inside neurons and causes damage to the neurons.
These tangles are one of the hallmarks of Alzheimer’s.
The senescent neurons also had high levels of a protein called cyclin-dependent kinase inhibitor 2D (CDKN2D/p19), which helps control whether a cell divides.
Like other senescent cells, the senescent neurons had larger nuclei than healthy cells, and the senescent neurons with neurofibrillary tangles had even larger nuclei.
The new study’s results suggest that drugs that target senescent cells might be effective treatment options for Alzheimer’s.
Future studies using this newly developed technique could also help researchers identify and analyze senescent cells in other tissues and organs.
Wellness
Gut-friendly foods may damage heart, charity warns
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Diabetes patients face increased risk of undiagnosed heart failure

People with diabetes may have undiagnosed heart failure that could be detected by a simple screening blood test, research suggests.
The TARTAN-HF trial found that one in four patients with diabetes who had at least one other risk factor for heart failure had undiagnosed heart failure detected through screening with a blood test and ultrasound scanning of the heart.
Experts said the findings show the extent of unrecognised heart failure in people with diabetes, and how the condition can be detected using a widely available blood test called NT-proBNP, which measures how much strain the heart is under.
They suggest a heart failure screening programme for diabetics could improve diagnosis rates, lead to earlier treatment and potentially reduce the risk of hospitalisation and death.
The study, involving 700 patients, was led by the University of Glasgow in collaboration with AstraZeneca, Roche Diagnostics, Us2.ai, NHS Greater Glasgow and Clyde and NHS Lanarkshire.
Dr Kieran Docherty, clinical senior lecturer at the University of Glasgow’s School of Cardiovascular and Metabolic Health, said: “Our results from the landmark TARTAN-HF trial identified heart failure in a large proportion of people living with diabetes, emphasising the need for a heart failure screening strategy in this group of patients.
“We know that many of the symptoms and signs of heart failure are non-specific, and may go unrecognised as potentially being due to heart failure for a long time.
“The strategy used in our trial is simple and easy to implement in clinical practice, and will aid in the early identification of heart failure in people with diabetes, and facilitate the initiation of medications that we know improve outcomes in patients with heart failure.”
The study, which began more than three years ago, involved more than 700 people with diabetes from the two health board areas who had at least one other risk factor for heart failure.
They were randomly assigned either to receive heart failure screening or to continue with their usual care.
Researchers found screening uncovered a large number of previously unrecognised cases of heart failure. Around one in four, or 24.9 per cent, of those screened were found to have the condition within six months, compared with 1 per cent in the group continuing their usual care.
The study, involving patients with type 1 and type 2 diabetes, found almost all of the participants found to have heart failure had preserved ejection fraction, which can be difficult to detect without dedicated testing.
The findings of the TARTAN-HF trial were presented at the American College of Cardiology conference taking place from 28 to 30 March in New Orleans in the US.
Dr Edward Piper, medical director at AstraZeneca UK, said: “Delayed diagnosis and treatment of heart failure in people with type 2 diabetes contributes to poor long-term outcomes. TARTAN-HF demonstrates that targeted, risk-based screening can identify previously undiagnosed heart failure in approximately one in four high-risk patients with diabetes, enabling earlier intervention with guideline-directed therapy.”
Dr Christian Simon, head of global medical affairs at Roche Diagnostics, said: “We are proud to have supported the landmark TARTAN-HF trial. These findings demonstrate the transformative power of early, accessible diagnostics like the NT-proBNP blood test.
“By identifying unrecognised heart failure in people with diabetes, we enable clinicians to initiate appropriate treatments sooner, ultimately improving patient outcomes and lives.”
News
UK government announces £6.3m fund to boost men’s health

The UK has launched a £6.3m men’s health fund to back local projects aimed at helping men and boys live longer, healthier lives.
The Men’s Health Community Fund is a partnership between the Department of Health and Social Care, Movember and People’s Health Trust.
The government is contributing £3m, while the two charities are more than doubling that to take the total to £6.3m.
Grants will support community projects reaching underserved men and boys aged 16 and over, particularly in the most disadvantaged areas and at key points in their lives such as becoming a father, losing a job or retiring.
Projects could include support for new fathers, activities for men facing loneliness and social isolation, services to help young men engage with the health system, and support for men in work, out of work and moving into retirement.
The programme will bring together voluntary, community and social enterprise organisations to test new ways of reaching men who are least likely to use traditional health services.
An evaluation funded through the National Institute for Health and Care Research will assess what works and help inform future policy and delivery.
Health and social care secretary Wes Streeting said: “Too many men across the country are living shorter, less healthy lives, particularly those in our most disadvantaged communities.
“This new partnership will help men get the support they need in the places they feel most comfortable, their communities, among people they trust.
“By working with expert charities and local organisations, we can reach the men who are too often missed by traditional services and help them take better care of their mental and physical health.”
“It is a key step in delivering our first ever Men’s Health Strategy and driving forward our ambition to halve the gap in healthy life expectancy between the richest and poorest areas.”
The Men’s Health Strategy sets out plans to tackle the physical and mental health challenges men and boys face.
Men can be less likely to seek help and more likely to suffer in silence, while higher rates of smoking, drinking, gambling and drug use are damaging men’s health and affecting families, workplaces and communities.
The government is also investing £3.6m over the next three years in suicide prevention projects for middle-aged men in local communities across areas of England where men are most at risk, many of which are also among the most deprived. Suicide is one of the biggest killers of men under 50, and three-quarters of all suicides are men.
The projects will aim to break down barriers middle-aged men face in seeking support, including stigma around asking for help and a lack of awareness of what is available and how to access it.
They will be co-designed with experts and men with lived experience of mental health crises and suicidal thoughts.
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