Tag: ageing

Cycling Can Improve Mobility in Myotonic Dystrophy

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Regular cycling can greatly improve mobility in patients with myotonic dystrophy (MD), an inherited genetic disease that causes muscle degeneration, according to research published in The Journal of Clinical Investigation. Professor Mark Tarnopolsky, senior author of the study, said that cycling for 35 minutes three times a week for 12 weeks led to a 32% increase in overall fitness in people with MD.

The participants also saw a 1.6-kilogram increase in their muscle mass and a two percent reduction of body fat. They were also able to walk an extra 47 metres in six minutes, when tested by researchers at the end of the 12-week trial.

The research team recruited 11 patients with MD to examine how effective cycling was in restoring and maintaining their physical health. Researchers also studied the underlying molecular mechanisms through which exercise strengthens the skeletal muscles, which can be severely weakened by MD.

“Exercise really is medicine – we just need to get the message out,” said Prof Tarnopolsky. “Myotonic dystrophy is a progressive condition that will impair your mobility and can put you in a wheelchair. There is no cure for it and only regular exercise helps you achieve better function.”

Prof Tarnopolsky said that some patients with MD are even advised by their doctors not to exercise, for fear of making their condition worse, but that is now proven false. 

Prior studies with mouse models showed a range of similar physiological benefits from regular exercise, the researchers said. MD is the most commonly diagnosed type of muscular dystrophy in adults, and the second most prevalent of all muscular dystrophies, noted Prof Tarnopolsky.

MD’s main symptoms include severe skeletal muscle atrophy, general muscle weakness, reduced lung capacity and impaired heart function. Other symptoms may include cataracts, endocrine disorders including diabetes and gastro-intestinal disorders. 

“MD itself is really a form of accelerated ageing,” said Prof Tarnopolsky.

Source: McMaster University

Fewer Types of Antibodies Produced with Age

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Using short-lived killifish to study how the immune system weakens with ageing, scientists have found that fewer types of antibodies are produced as organisms age. Published in eLife, the findings could lead to ways to rejuvenate the immune systems of older people.

The immune system has to constantly respond to new attacks from pathogens and remember them in order to be protected during the next infection. For this purpose, B cells build a library of information that can produce a variety of antibodies to recognise the pathogens.

“We wanted to know about the antibody repertoire in old age,” explained lead researcher Dario Riccardo Valenzano. “It is difficult to study a human being’s immune system over his or her entire life, because humans live a very long time. Moreover, in humans you can only study the antibodies in peripheral blood, as it is problematic to get samples from other tissues. For this reason, we used the killifish. It is very short-lived and we can get probes from different tissues.”

The shortest-lived vertebrates that can be kept in the laboratory, killifishes quickly age over their three to four month lifespan and have become the focus of ageing research in recent years due to these characteristics.

The researchers were able to accurately characterise all the antibodies that killifish produce. They found that older killifish have different types of antibodies in their blood than younger fish. They also had a lower diversity of antibodies throughout their bodies.

The discovery could lead to ways to rejuvenate the immune system. “If we have fewer different antibodies as we age, this could lead to a reduced ability to respond to infections. We now want to further investigate why the B cells lose their ability to produce diverse antibodies and whether they can possibly be rejuvenated in the killifish and thus regain this ability,” Valenzano said.

Source: Max Planck Institute for Biology of Ageing

Overtreatment for Diabetes among Nursing Home Residents

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Nursing home residents with diabetes are at high risk of having hypoglycaemia if their diabetes is overtreated, finds a new study published in the Journal of the American Geriatrics Society. The research suggests that many residents of nursing homes continue to receive insulin and other medications that increase hypoglycaemia risk even after blood tests suggest overtreatment.

Among 7422 nursing home residents, most had blood test results at the start of the study suggesting tight control of their blood sugar levels, and most were on insulin. Only 27% of overtreated and 19% of potentially overtreated residents at baseline had their medication regimens deintensified within 2 weeks.

Long-acting insulin use and hyperglycaemia ≥300 mg/dL before index HbA1c were associated with increased odds of continued overtreatment. Severe functional impairment (MDS-ADL score ≥ 19) was associated with decreased odds of continued overtreatment Hypoglycaemia was not associated with decreased odds of overtreatment.

The researchers suggested that deprescribing initiatives targeting residents at high risk of harms and with low likelihood of benefit, such as those with history of hypoglycaemia, or high levels of cognitive or functional impairment are most likely to identify nursing home residents most likely to benefit from deintensification.

“I hope this work lays the foundation for future projects that promote appropriate deintensification of glucose lowering medications in nursing home residents,” said lead author Lauren I. Lederle, MD, of the San Francisco VA Medical Center.

Source: Wiley

An AI ‘Storytelling’ Companion to Assist Dementia Patients

Researchers at the National Robotarium in the UK, are developing an artificial intelligence (AI) ‘storytelling’ companion that will aid memory recollection, boost confidence and combat depression in patients suffering from Alzheimer’s disease and other types of dementia.

The idea for the ground-breaking ‘Agent-based Memory Prosthesis to Encourage Reminiscing’ (AMPER) project came from Dr Mei Yii Lim, a co-investigator of the project and an experienced memory modelling researcher.

In Alzheimer’s patients, memory loss occurs in reverse chronological order, with pockets of long-term memory remaining accessible even as the disease progresses. Rehabilitative care methods currently focus on physical aids and repetitive reminding techniques, but AMPER’s AI-driven user-centred approach will instead focus on personalised storytelling to help bring a patient’s memories back to the surface.

Dr Lim explained the project: “AMPER will explore the potential for AI to help access an individual’s personal memories residing in the still viable regions of the brain by creating natural, relatable stories. These will be tailored to their unique life experiences, age, social context and changing needs to encourage reminiscing.”

Having communication difficulties and decreased confidence are commonly experienced by people living with dementia and can often lead to individuals becoming withdrawn or depressed. By using AI to aid memory recollection, researchers at the National Robotarium hope that an individual’s sense of value, importance and belonging can be restored and quality of life improved.

The project’s long-term vision is to show that AI companions can become more widely used and integrated into domestic, educational, health and assistive-needs settings.

Professor Ruth Aylett from the National Robotarium is leading the research. She said: “One of the most difficult aspects of living with dementia can be changes in behavior caused by confusion or distress. We know that people can experience very different symptoms that require a range of support responses. Current intervention platforms used to aid memory recollection often take a one-size-fits-all approach that isn’t always suitable to an individual’s unique needs.”

“AI technology has the potential to play a pivotal role in improving the lives of people living with cognitive diseases. Our ambition is to develop an AI-driven companion that offers patients and their caregivers a flexible solution to help give an individual a sustained sense of self-worth, social acceptance and independence.

“Through projects like AMPER, we’re able to highlight the many ways AI and robotics can both help and improve life for people now and in the future. At the National Robotarium, we’re working on research that will benefit people in adult care settings as well as across a wide range of other sectors that will make life easier, safer and more supported for people.”

Once developed, the AI technology will be accessed through a tablet-based interface to make it more widely accessible and low-cost. The National Robotarium team will also investigate a using the AI in a desktop robot to see if a physical presence has any benefit.

Source: Heriot Watt University

Cells in Mice Partially Reset to More Youthful States

Mouse
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Scientists have shown that they can safely and effectively reverse the epigenetic markers of age in middle-aged and elderly mice by partially resetting their cells to more youthful states – reducing many signs of ageing as they do so.

As organisms age, their cells have different epigenetic markers on their DNA compared to younger ones. It is known that adding a mixture of reprogramming molecules, also known as ‘Yamanaka factors’, to cells can reset these epigenetic marks to their original patterns. This approach enables researchers to turn back the clock for adult cells, developmentally speaking, into stem cells.

“We are elated that we can use this approach across the life span to slow down aging in normal animals. The technique is both safe and effective in mice,” said Juan Carlos Izpisua Belmonte, co-corresponding author, professor at the Salk Institute. “In addition to tackling age-related diseases, this approach may provide the biomedical community with a new tool to restore tissue and organismal health by improving cell function and resilience in different disease situations, such as neurodegenerative diseases.”

The Salk Institute research lab reported in 2016 that, for the first time, they were able use the Yamanaka factors to counter the signs of aging and increase life span in mice with a premature ageing disease. More recently, the lab found that the Yamanaka factors can accelerate muscle regeneration even in younger mice. Building on these studies, other scientists have used the same approach to improve the function of other tissues like the heart, brain and optic nerve.

In the new study, the researchers tested variations of the cellular rejuvenation approach in healthy animals as they aged. One group of mice received regular doses of the Yamanaka factors from the time they were 15 months old until 22 months, approximately equivalent to age 50 through 70 in humans. Another group was treated from 12 through 22 months, approximately age 35 to 70 in humans. And a third group was treated for just one month at age 25 months, similar to age 80 in humans.

“What we really wanted to establish was that using this approach for a longer time span is safe,” said Pradeep Reddy, study co-first author. “Indeed, we did not see any negative effects on the health, behaviour or body weight of these animals.”

No blood cell alterations or neurological changes were seen in the mice treated with the Yamanaka factors compared to control mice. Additionally, no cancers were observed in any of the groups of animals.

In terms of normal signs of ageing, the treated mice resembled younger animals in a number of ways. In both the kidneys and skin, the epigenetics of treated animals more closely resembled epigenetic patterns seen in younger animals. When injured, the skin cells of treated animals had a greater ability to proliferate and were less likely to form permanent scars, unlike normal older animals. Metabolic molecules also did not reflect normal age-related changes.

This youthfulness was observed in the animals treated for seven or 10 months with the Yamanaka factors, but not the animals treated for just one month. What’s more, when the treated animals were analysed midway through their treatment, the effects were not yet as evident. This suggests that the treatment is not simply pausing aging, but actively turning it backwards–- although more research is needed to differentiate between the two.

The team is now planning future research to analyse how specific molecules and genes are changed by long-term treatment with the Yamanaka factors. They are also developing new ways of delivering the factors.

“At the end of the day, we want to bring resilience and function back to older cells so that they are more resistant to stress, injury and disease,” said Reddy. “This study shows that, at least in mice, there’s a path forward to achieving that.”

The study was published in Nature Aging.

Source: Salk Institute

Factors that Affect Disability after Surgery in Older Adults

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In an analysis of older adults who underwent surgery, published in the Journal of the American Geriatrics Society, more who had non-elective surgery were found to experience disabilities than those who had elective surgery, and factors such as age increased this vulnerability.

The study included 247 adults aged 70 years or older who were discharged from the hospital after major surgery from 1997 to 2017, patients who had non-elective surgery had more disabilities in daily activities over the following 6 months than those who had elective surgery.  

Researchers identified 10 factors that were associated with greater disability burden: age 85 years or older, female sex, Black race or Hispanic ethnicity, neighbourhood disadvantage, multimorbidity, frailty, one or more disabilities, low functional self-efficacy, smoking, and obesity. The burden of disability increased with each additional “vulnerability” factor.

“The results from this study can be used by clinicians to identify older adults who are particularly susceptible to poor functional outcomes after major surgery, and a subset of the factors identified could serve as the basis for new interventions to improve functional outcomes in vulnerable older surgical patients,” said lead author Thomas M. Gill, MD, of the Yale School of Medicine.

Source: Wiley

Higher Oestrogen Levels Protect Older Women Against Severe COVID

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An older woman’s oestrogen levels may be linked to her chances of dying from COVID, with higher levels of the hormone seemingly protective against severe infection, according to a study published in BMJ Open.

Supplemental hormone treatment to curb the severity of COVID infection in post-menopausal women could be investigated, the researchers suggested.

Even after accounting for other factors, women seem to have a lower risk of severe COVID infection than men. This holds true for other serious recent viral infections, such as MERS (Middle East Respiratory Syndrome).

Oestrogen may have a role in this gender discrepancy, so to invesitgate the researchers compared the potential effects of boosting and reducing oestrogen levels on COVID infection severity.

They drew on Swedish national data, and the study sample included 14 685 women in total: 227 (2%) had been previously diagnosed with breast cancer and were on oestrogen blocker drugs (adjuvant therapy) to curb the risk of cancer recurrence; and 2535 (17%) were taking hormone replacement therapy (HRT) to boost their oestrogen levels in a bid to relieve menopausal symptoms.

Some 11,923 (81%) women acted as the comparison group as they weren’t on any type of treatment, either to enhance or reduce their systemic oestrogen levels.

Analysis of all the data showed that compared with no oestrogen treatment, the crude odds of dying from COVID were twice as high among women on oestrogen blockers but 54% lower among women on HRT.

After accounting for potentially influential factors, COVID mortality risk remained significantly lower (53%) for women on HRT.

Unsurprisingly, age was significantly associated with COVID mortality risk, with each extra year associated with 15% greater odds, while every additional coexisting condition increased the odds of death by 13%.

And those with the lowest household incomes were nearly 3 times as likely to die as those with the highest.

As an observational study, it cannot establish cause. There were no data on the precise doses of HRT or oestrogen blocker drugs, or their duration, nor on weight or smoking, while the number of women on adjuvant therapy was relatively small.

These factors may have been influential. But the researchers conclude: “This study shows an association between oestrogen levels and COVID death. Consequently, drugs increasing oestrogen levels may have a role in therapeutic efforts to alleviate COVID severity in postmenopausal women and could be studied in randomised control trials.”

Source: EurekAlert!

Improving Attitudes to Ageing Measurably Improves Health

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Helping people feel better about how they are ageing could result in real improvements in health and well-being later on, according to research from the University of British Columbia which was published in JAMA Network Open.

Over a four-year period, researchers tracked changes in how participants felt about their own ageing, then looked for measurable changes in health and well-being after another four years had passed. Those participants whose attitudes had improved over the first four years were more likely to have measurable health improvements in the next four years.

“Prior research has looked at how psychological risk factors like depression and stress might adversely influence health and well-being outcomes, but we are interested in factors that might positively influence health and well-being outcomes,” said Julia Nakamura, a graduate student in UBC’s department of psychology and first author of the study. “With further research, our findings suggest that interventions to increase aging satisfaction might improve the health and well-being of our rapidly growing older adult population.”

Health and well-being are gaining favor as indicators of societal progress, over pure economic indicators. Governments and intergovernmental organisations have recognised that using gross domestic product as the primary measure of success can lead to policies that devalue environmental, psychological and social health. Increasingly, they are looking for more holistic ways to measure societal well-being.

In this study, more than 13 000 adults over age 50 contributed data through the Health and Retirement Study in the U.S. between 2008 and 2018. The research team analysed participants’ data at three separate intervals, four years apart.

At the first interval, the researchers recorded initial measures of health and well-being. They also captured aging satisfaction through participants’ responses to statements such as:

  • Things keep getting worse as I get older.
  • I am as happy now as I was when I was younger.
  • The older I get, the more useless I feel.

At the second interval, they assessed ageing satisfaction again.

At the third and final interval, they measured how health and well-being measures had changed four years after the second measurement of aging satisfaction.

Of the 35 outcomes they measured, 27 had improved in association with improved aging satisfaction four years earlier. Decreases in ageing satisfaction from the first to second interval were associated with worsening health and well-being outcomes by the third interval.

The order in which these measurements were taken is important. People in better health could be expected to have more positive attitudes about ageing than those with health problems, but this analysis in fact showed that increases in ageing satisfaction clearly preceded improvements in health and well-being.

“Interventions that make people feel better about aging could potentially produce concrete benefits,” said Nakamura. “Those interventions could come at both the individual level and the broader, societal level. At the societal level, combating ageism and reducing harmful stereotypes about aging are potential paths to improving individual aging satisfaction. If a person thinks ageing is destined to be a negative experience, that might become a self-fulfilling prophecy.”

Source: University of British Columbia

Intensive Hypertension Treatment may Prevent Strokes in Older Adults

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More intensive hypertension treatment could help prevent or delay strokes in older adults, according to an analysis of results from randomised clinical trials published in the Journal of the American Geriatrics Society.

The researchers initially screened 22 trials for inclusion. Nine trials involving 38 779 adults with an average age ranging from 66 to 84 years were included in the analysis, with follow-up times ranging from 2.0 to 5.8 years.

On average, the researchers found that it took 1.7 years to prevent 1 stroke for 200 older persons treated with more intensive hypertension treatment.

For older adults with baseline systolic blood pressures below 150 mmHg, the time to benefit from more intensive hypertension treatment was longer than 1.7 years; for older adults with baseline systolic blood pressure above 190 mmHg, the time to benefit was shorter than 1.7 years.

In their discussion, the researchers noted the risks of aggressive hypertension treatment, including hypotension, syncope and falls. However, they noted that emerging evidence shows that the increase in fall risk is transient.

“While the 2017 American College of Cardiology/American Heart Association guidelines recommend individual risk discussions about hypertension treatment for primary prevention in older adults, there is a critical gap in data about how long a patient needs to receive blood pressure treatment before they will benefit – or the blood pressure treatment’s time to benefit,” said lead author Vanessa S. Ho, MS, of California Northstate University College of Medicine. “A treatment’s time to benefit is an especially important consideration for patients with a limited life expectancy who may experience immediate burdens or harms from any additional medication.”

Source: Wiley

Two Key Proteins with a Major Role in Ageing

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In the largest genetic study of ageing to date, two key proteins have been identified that play a significant role in the ageing process. Developing drugs that target these proteins could be one way of slowing down ageing.

Genetics, lifestyle, environment and chance influence ageing. The study sheds light on the part proteins play in this process. Some people have higher or lower levels of certain proteins according to their individual DNA, which in turn affect a person’s health.

In a study published in Nature Aging, researchers from the University of Edinburgh combined the results of six large genetic studies into human ageing – each containing genetic information on hundreds of thousands of people.

Among 857 proteins studied, researchers identified two that had significant negative effects across various ageing measures.

People who inherited DNA that causes raised levels of these proteins were frailer, had poorer self-rated health and were less likely to live an exceptionally long life than those who did not.

The first protein, apolipoprotein(a) (LPA), is made in the liver and thought to play a role in clotting. High levels of LPA can increase the risk of atherosclerosis – a condition in which arteries become clogged with fatty substances. Heart disease and stroke is a possible outcome.

The second protein, vascular cell adhesion molecule 1 (VCAM1), is primarily found on the surfaces of endothelial cells lining blood vessels. The protein controls the vessels’ expansion and retraction – and have a function in blood clotting and the immune response.

Levels of VCAM1 increase in response to signals indicating an infection, and the protein then allows immune cells to cross the endothelial layer.

The researchers say that drugs used to treat diseases by reducing levels of LPA and VCAM1 could have the added benefit of improving quality and length of life.  

One such example is a clinical trial that is testing a drug to lower LPA as a way of reducing the risk of heart disease. No clinical trials with VCAM1 are underway, but studies in mice have shown how antibodies lowering this protein’s level improved cognition during old age.

The identification of these two key proteins could help extend the healthy years of life. Drugs that reduce these protein levels in the blood could allow the average person to live as healthy and as long as individuals who have won the genetic lottery and are born with genetically low LPA and VCAM1 levels.

Source: University of Edinburgh