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Scientists discover new way to fight the ageing process

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New findings could allow experts to improve DNA repair in body cells and target the causes of ageing and cancer development.

A protein complex prevents the repair of genome damage in human cells, in mice and in the nematode Caenorhabditis elegans, a team of researchers at the University of Cologne has discovered.

They also successfully inhibited this complex for the first time using a pharmaceutical agent.

As it contains all of our genetic information, our DNA must be well protected. However, it constantly faces damage caused by environmental influences – or our normal metabolism. Hence, DNA repair is essential for the stability of our genome and the functioning of our cells.

“When we suppress the so-called DREAM complex in body cells, various repair mechanisms kick in, making these cells extremely resilient towards all kinds of DNA damage,” said Professor Dr Björn Schumacher, director of the Institute for Genome Stability in Aging and Disease at the University of Cologne’s CECAD Cluster of Excellence in Aging Research.

“Our findings for the first time allow us to improve DNA repair in body cells and to target the causes of ageing and cancer development.”

Still, more research is needed until these results can be translated into new therapies for human patients. 

The study ‘The DREAM complex functions as conserved master regulator of somatic DNA repair capacities’ has appeared in Nature Structural & Molecular Biology.

DNA-damage leads to ageing and disease

Our genetic material is passed on from generation to generation. That is why it is particularly well protected in our germ cells. Highly precise DNA repair mechanisms are at work there, ensuring that only very few changes in the genetic material are passed onto offspring. Thanks to DNA repair, our human genome has been passed on to us by our ancestors for two hundred thousand years. It has always ensured that the genetic information is preserved. DNA is also constantly repaired in our body cells, but only for the duration of the individual’s life.

Sometimes, children are born with faulty DNA repair systems, making them age more quickly and develop typical age-related diseases such as neuro-degradation and arteriosclerosis already in childhood. In some cases, they also have an extremely increased risk of cancer. These are all consequences of DNA damage not being properly repaired.

The DREAM complex prevents repairs

Schumacher and his team explored why body cells do not have the same repair mechanisms as germ cells. In experiments with the nematode C. elegans, they found out that the DREAM protein complex limits the quantity of DNA repair mechanisms in body cells: the complex attaches to the DNA’s construction plans containing instructions for the repair mechanisms. 

This prevents them from being produced in large quantities. Germ cells, however, do not have the DREAM complex. Hence, they naturally produce large quantities of DNA repair mechanisms.

Mammals also have a DREAM-complex

In further experiments with human cells in the laboratory (cell culture), the scientists showed that the DREAM complex functions in the same way in human cells. They were also able to override the DREAM complex with a pharmaceutical agent. 

“We were very pleased to see the same effect as we did in C. elegans. The human cells were much more resilient towards DNA damage after treatment,” said Arturo Bujarrabal, a postdoc in Schumacher’s team and lead author of the study. 

Treatment with the DREAM complex inhibitor also showed amazing effects in mice: The DNA in the retina of mice could be repaired and the function of the eye preserved. The test was carried out in mice that, like some patients, age prematurely and show a typical degeneration of the eye’s retina.

DNA-damage in space

Genome damage also plays a major role in manned spaceflight because of the extremely high radiation in space. 

A longer stay in space without improved DNA repair is hardly imaginable.

Schumacher sums up: “Therapies that target and improve this newly discovered master regulator of DNA repair could reduce the risk of cancer because genes remain intact.” 

In addition, the risk of age-related diseases would be reduced because cells can only fulfil their function with an intact genome.

The study was carried out at the Institute for Genome Stability in Aging and Disease of the University of Cologne’s CECAD Cluster of Excellence in Aging Research.

 

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Air pollution linked to increased hospital admission for heart and lung diseases

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Exposure to fine particulate matter (PM2.5) air pollution is linked to an increased risk of hospital admission for major heart and lung diseases, find two large US studies, published by The BMJ.

Together, the results suggest that no safe threshold exists for heart and lung health.

According to the Global Burden of Disease study, exposure to PM2.5 accounts for an estimated 7.6% of total global mortality and 4.2% of global disability adjusted life years (a measure of years lived in good health).

In light of this extensive evidence, the World Health Organization (WHO) updated the air quality guidelines in 2021, recommending that an annual average PM2.5 levels should not exceed 5 μg/m3 and 24 hour average PM2.5 levels should not exceed 15 μg/m3 on more than 3-4 days each year.

In the first study, researchers linked average daily PM2.5 levels to residential zip codes for nearly 60 million US adults (84 per cent white, 55 per cent women) aged 65 and over from 2000 to 2016. They then used Medicare insurance data to track hospital admissions over an average of eight years.

After accounting for a range of economic, health and social factors, average PM2.5 exposure over three years was associated with increased risks of first hospital admissions for seven major types of cardiovascular disease – ischemic heart disease, cerebrovascular disease, heart failure, cardiomyopathy, arrhythmia, valvular heart disease, and thoracic and abdominal aortic aneurysms.

Compared with exposures of 5 μg/m3 or less (the WHO air quality guideline for annual PM2.5), exposures between 9 and 10 μg/m3, which encompassed the US national average of 9.7 μg/m3 during the study period, were associated with a 29% increased risk of hospital admission for cardiovascular disease.

On an absolute scale, the risk of hospital admission for cardiovascular disease increased from 2.59% with exposures of 5 μg/m3 or less to 3.35% at exposures between 9 and 10 μg/m3.

“This means that if we were able to manage to reduce annual PM2.5 below 5 µg/m3, we could avoid 23% in hospital admissions for cardiovascular disease,” say the researchers.*

These cardiovascular effects persisted for at least three years after exposure to PM2.5, and susceptibility varied by age, education, access to healthcare services, and area deprivation level.

The researchers say their findings suggest that no safe threshold exists for the chronic effect of PM2.5 on overall cardiovascular health, and that substantial benefits could be attained through adherence to the WHO air quality guideline.

“On February 7, 2024, the US Environmental Protection Agency (EPA) updated the national air quality standard for annual PM2.5 level, setting a stricter limit at no more than 9 µg/m3. This is the first update since 2012. However, it is still considerably higher than the 5 µg/m3 set by WHO. Obviously, the newly published national standard was not sufficient for the protection of public health,” they add.*

In the second study, researchers used county-level daily PM2.5 concentrations and medical claims data to track hospital admissions and emergency department visits for natural causes, cardiovascular disease, and respiratory disease for 50 million US adults aged 18 and over from 2010 to 2016.

During the study period, more than 10 million hospital admissions and 24 million emergency department visits were recorded.

They found that short term exposure to PM2.5, even at concentrations below the new WHO air quality guideline limit, was statistically significantly associated with higher rates of hospital admissions for natural causes, cardiovascular disease and respiratory disease, as well as emergency department visits for respiratory disease.

For example, on days when daily PM2.5 levels were below the new WHO air quality guideline limit of 15 μg/m3, an increase of 10 μg/m3 in PM2.5 was associated with 1.87 extra hospital admissions per million adults aged 18 and over per day.

The researchers say their findings constitute an important contribution to the debate about the revision of air quality limits, guidelines, and standards.

Both research teams acknowledge several limitations such as possible misclassification of exposure and point out that other unmeasured factors may have affected their results. What’s more, the findings may not apply to individuals without medical insurance, children and adolescents, and those living outside the US.

However, taken together, these new results provide valuable reference for future national air pollution standards.

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Home health care linked to increased hospice use at end-of-life – study

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Patients who had previously received home health care had a higher likelihood of accessing hospice care at the end of their life, according to a new study.

Researchers, whose findings are published in the Journal of Palliative Medicine, examined the home health care and hospice care experiences of more than two million people.

Using Medicare data, researchers found when individuals received home health care before the last year of their life, they had higher odds of using hospice care than those who had never received home health care.

Researchers said this association underscores the potential benefits of receiving end-of-life care in the comfort of one’s home.

As the aged population increases, the findings also show the need for more resources in the health care sector and staff training in end-of-life care.

Home health care services including skilled nursing, therapy, social work and aide services are used to maintain functioning or slow decline in health. Hospice care provides similar services but is intended for those with life expectancies of six months or less and is focused on pain relief, minimising hospital visits and providing comfort and support. Both services provide patients the opportunity to receive more personalised care in their home.

Researchers say home-based care also encourages greater involvement of family caregivers in the caregiving process.

Olga Jarrín, senior author of the study, the Hunterdon Professor of Nursing Research at the Rutgers School of Nursing and director of the Community Health and Aging Outcomes Laboratory within the Rutgers Institute for Health, Health Care Policy and Aging Research, commented: “In addition to benefits for the patient, hospice care also provides resources and support to help family caregivers cope with the physical, emotional and practical challenges of caring for a loved one at the end of life.”

Hyosin (Dawn) Kim, research assistant professor at Oregon State University and first author of the study, added: “By providing personalised care, reducing hospitalisations, fostering family involvement and support, and improving symptom management, home-based care can enhance the quality of end-of-life experiences for patients with terminal illnesses and their families.”

 

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Sleep programme shows promise in those with memory problems – study

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A new study has shown promising results in improving sleep and quality of life in individuals living with memory problems.

A group of researchers from Penn Nursing, Penn Medicine, Rutgers School of Nursing, and Drexel University’s College of Nursing and Health Professions, have delved into the efficacy of a non-pharmacological approach in a trial known as the Healthy Patterns Sleep Program.

The study involved 209 pairings of community-residing individuals with memory problems and their care partners. Participants were assigned to either the Healthy Patterns Sleep Program, which consisted of one-hour home activity sessions administered over four weeks, or a control group that received sleep hygiene training, plus education on home safety and health promotion.

The Healthy Patterns Sleep Program trained care partners in timed daily activities such as reminiscence in the morning, exercise in the afternoon and sensory activities in the evening that can decrease daytime sleepiness and improve nighttime sleep quality.

Nancy Hodgson, PhD, RN, FAAN, the Claire M. Fagin Leadership Professor in Nursing and Chair of Department of Biobehavioral Health Sciences, who led the study, said: “The results from this study provide fundamental new knowledge regarding the effects of timing activity participation and can lead to structured, replicable treatment protocols to address sleep disturbances. Overall, the Healthy Patterns program resulted in improved QOL compared to an attention-control group.”

The findings also indicate that, compared to a control group, the four-week Healthy Patterns program improved sleep quality among persons living with memory issues who had depressive symptoms or poor sleep quality.  The study indicates the Healthy Patterns Intervention might need a longer dose to induce improvements in other sleep-wake activity metrics.

The study’s significance lies in its confirmation of the effectiveness of behavioural interventions in not only improving quality of life and addressing sleep quality issues in this population, but also potentially reducing care partner burden and overall care costs for persons living at home with memory problems.

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