Category: Ageing

CSF From Young Mice Improves Memory of Older Mice

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In a finding reminiscent of how vampires and zombies in fiction get sustenance from their victims, a team of researchers reported in the journal Nature that injecting cerebrospinal fluid (CSF) from young mice into old mice improves the memory and cognitive abilities of the older mice

Such an approach is nothing new, although the chief obstacle was safely harvesting such a tiny amount of CSF from the small animals. About two decades ago, studies had reported that transferring blood from younger mice to older ones notably improved the health of the older mice, giving them a ‘rejuvenating’ effect. It did not take long for people to take note of this discovery, with a startup company offering transfers of young people’s plasma for exorbitant amounts to wealthy older clients in the unproven hopes of reversing ageing. Fears of a dystopian future were averted when the US Food and Drug Administration released a statement stating such transfers had no clinical benefit, and the company folded. However, research continued.

Since ageing is too complex to measure in a clinical trial anyway, scientists have been focusing on tackling specific aspects of it, such as in neurodegenerative diseases like Alzheimer’s and research has continued in this direction. A few years ago, human umbilical cord plasma was shown to revitalise hippocampal function in aged mice, and previous work led by Tony Wryss-Coray, PhD had found that young mouse blood improved age-related impairments in cognition. Studies of fear conditioning had shown that proliferation of oligodendrocyte precursor cells (OPCs) was necessary for fear formation, which raised the question of whether CSF might affect this.

Infusing CSF taken from 10 week old mice over seven days, researchers trained 18 month old mice to associate a flashing light with an electric shock to the foot. The CSF infusion was shown to improve recall of the fear stimulus in the older mice and induce greater OPC proliferation.

“The broad message here is that the aging process is malleable, which of course is not new because of this paper,” senior author Dr Wyss-Coray said in an interview with MedPage Today. “But it adds to the idea that aging is a potential therapeutic target, a process we can start to understand better and start to manipulate.”

“The other message – one that’s more brain-specific – is that if you improve the environment in which neurons live, you can actually have a substantial improvement in function,” he added. “That may be as important, or even more important sometimes, than targeting neuronal processes themselves.”

The researchers isolated fibroblast growth factor 17 (Fgf17) infusion as being necessary for OPC proliferation, and blocking it in young mice impaired cognition.

“This suggests that Fgf17 is not only able to recapitulate some of the useful effects of CSF from young mice, but it also seems to be necessary to make a young brain function at its full capacity,” Dr Wyss-Coray said.

Genetic Risk Score for Hip or Knee Replacements

A Monash University-led research team has developed a risk score based on individuals’ genetic data to predict their likelihood of needing hip or knee replacement surgery for osteoarthritis. The team validated the score’s predictive ability in a study published in Arthritis & Rheumatology.  

The score incorporates 10 genetic sequence variants for predicting a person’s risk of needing knee replacement surgery and 37 genetic sequence variants for predicting the risk of needing hip replacement surgery.  

Among 12093 individuals of European genetic descent aged 70 years or older, 1422 (11.8%) had knee replacements and 1,297 (10.7%) had hip replacements. Participants with high risk scores had a 1.44-times higher odds of knee replacement and a 1.88-times higher odds of hip replacement, compared with those with low risk scores.   

 “Genetic scores, such as the one we developed, do not change over a person’s life. They provide an individual  with further information about their risk of severe osteoarthritis in later life and have the potential to improve prevention of severe knee and hip osteoarthritis by identifying those who may benefit from early intervention,” said senior author Flavia Cicuttini, PhD, of Monash University.  

Source: Wiley

Osteoporosis in Men is Often Overlooked

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Osteoporosis in men is often overlooked by health care professionals, found the authors of a review published in The Lancet Diabetes and Endocrinology. There is a desperate need for raising awareness of the condition in men to help improve outcomes for patients, the authors said.

Women are generally at higher risk of developing osteoporosis, as their bone density declines more rapidly than men at an earlier age, especially post-menopause. In most populations, men have larger and stronger bone and joint surfaces, so they can be overlooked when diagnosing the condition.

Reviewing available data on the condition in men, researchers found that they are generally diagnosed later, comply with treatment less and present to hospital in older ages than women. With fatality rates from hospitalisations with fragility fractures, like a broken hip, being higher than women.

The review’s author, Dr Tatiane Vilaca, said: “Generally diagnosis of osteoporosis happens when a patient presents at hospital with some kind of fragility fracture in older age, for example falling from standing height, and breaking a hip, wrist or spine.

“Research suggests men hospitalised with hip fractures tend to be older than women, which could be because the condition develops more slowly in men. As older people are usually slightly frailer, with poorer states of overall health, this could explain the slightly higher levels of disability and mortality associated in men with osteoporosis who are hospitalised following a fracture.”

The review found that although there is a lack of research about which treatment options are most effective in men, diagnosis and treatment options are effective.

The team believe further research specifically tailored to osteoporosis in male patients will help improve current diagnosis systems, helping clinicians with earlier diagnosis, and a focus on education for patients will support compliance with drug treatment programs, all improving outcomes for men living with osteoporosis.

Dr. Richard Eastell, Professor of Bone Metabolism at the Department of Oncology and Metabolism, said: “As women make up larger numbers of people living with osteoporosis, the data we have on the progression of the condition in men is currently not as robust. This updated review shows that further studies of male patients could help improve current diagnosis systems, as well as resources for the education of primary care clinicians and the general public on the early warning signs of osteoporosis in men.”

Dr. Vilaca added: “Despite the current gap in knowledge, men can still easily be screened for osteoporosis at their general practitioner surgery.

“Anyone with a family history of osteoporosis, broken bones, or fractures, those with acute back pain or a loss of height should be encouraged to have a check-up.

“These are all early warning signs of the condition in both men and women, and early preventative treatment is the best way to ensure a slower disease progression and longer, healthier life without a fracture.”

Source: University of Sheffield

Seven Hours’ Sleep is Optimal in Middle Age and Older

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According to research published in Nature Aging, seven hours is the ideal amount of sleep for people in their middle age and upwards, with too little or too much little sleep associated with poorer cognitive performance and mental health.

Sleep plays an important role in enabling cognitive function and maintaining good psychological health, and also removes waste products from the brain. Alterations in sleep patterns appear during ageing, including difficulty falling asleep and staying asleep, and decreased quantity and quality of sleep. It is thought that these sleep disturbances may contribute to cognitive decline and psychiatric disorders in the ageing population.

Scientists from the UK and China examined data from nearly 500 000 adults aged 38–73 years from the UK Biobank. Participants were asked about their sleeping patterns, mental health and wellbeing, and took part in a series of cognitive tests. Brain imaging and genetic data were available for almost 40 000 of the study participants.

The researchers found in their analysis that both insufficient and excessive sleep duration were associated with impaired cognitive performance, such as processing speed, visual attention, memory and problem-solving skills. The optimal amount of sleep was found to be seven hours per night for cognitive performance and good mental health. More symptoms of anxiety and depression and worse overall wellbeing were associated with sleeping for longer or shorter durations.

The researchers say one possible reason for the association between insufficient sleep and cognitive decline may be due to the disruption of slow-wave — ‘deep’ — sleep. Disruption to this type of sleep has been shown to have a close link with memory consolidation as well as the build-up of amyloid — a key protein which, when it misfolds, can cause ‘tangles’ in the brain characteristic of some forms of dementia. Additionally, lack of sleep may hamper the brain’s ability to rid itself of toxins.

The amount of sleep was also linked differences in the structure of brain regions involved in cognitive processing and memory, again with greater changes associated with greater than or less than seven hours of sleep.

Consistently getting seven hours’ sleep each night was also important to cognitive performance and good mental health and wellbeing. Interrupted sleep patterns have previously been shown to be associated with increased inflammation, indicating a susceptibility to age-related diseases in older people.

Professor Jianfeng Feng from Fudan University in China said: “While we can’t say conclusively that too little or too much sleep causes cognitive problems, our analysis looking at individuals over a longer period of time appears to support this idea. But the reasons why older people have poorer sleep appear to be complex, influenced by a combination of our genetic makeup and the structure of our brains.”

The researchers say the findings suggest that insufficient or excessive sleep duration may be a risk factor for cognitive decline in ageing. This is supported by previous studies that have reported a link between sleep duration and the risk of developing Alzheimer’s disease and dementia, in which cognitive decline is a hallmark symptom.

Professor Barbara Sahakian from the Department of Psychiatry at the University of Cambridge, one of the study’s authors, said: “Getting a good night’s sleep is important at all stages of life, but particularly as we age. Finding ways to improve sleep for older people could be crucial to helping them maintain good mental health and wellbeing and avoiding cognitive decline, particularly for patients with psychiatric disorders and dementias.”

Source: University of Cambridge

Online Tool Helps Older Adults Decide When to Stop Driving

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A recent randomised controlled trial published in the Journal of the American Geriatrics Society found that an online decision aid may help older adults decide whether and when to stop driving.

Compared with older adults who viewed an educational website, those who viewed the decision aid, called Healthwise® DDA, had lower decisional conflict and higher knowledge about whether to stop or continue driving. The online aid has six sections: “Get the Facts,” “Compare Options,” “Your Feelings,” “Your Decision,” “Quiz Yourself,” and “Your Summary.”

In the National Institute on Aging–funded trial of 301 participants aged 70 years and older, 51.2% of whom identified as female,. the tool had high acceptability, with nearly all of those who used it saying that they would recommend it to others.

“The decision about when to stop driving is a difficult and emotional one – and also one most older adults eventually face,” explained lead author Marian Betz, MD, MPH, of the University of Colorado and the Rocky Mountain Regional VA Medical Center. “Tools like this one may help older adults make the decision and, hopefully, reduce negative feelings about the process.”

Source: Wiley

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

Cells in Mice Partially Reset to More Youthful States

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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

Why Knee Osteoarthritis Risk is Higher in Women

By using a bioreactor aboard a flight that simulated zero gravity, researchers have found that the reason why women have a greater risk of developing knee osteoarthritis is down to genetic differences in knee meniscus tissue.

Better tests, prevention and treatments could be developed for knee osteoarthritis in women here on Earth, based on this research.

Though knee osteoarthritis is more common in females than in males, the difference cannot be explained solely by hormones. The researchers have pinpointed a genetic difference in the meniscus that makes about 50% of females more vulnerable to developing osteoarthritis than males or other females. Exposure to zero gravity is known to mimic the ageing process, as muscles atrophy and bones lose density. The zero gravity environment of space has greatly contributed to medical research.

Researchers ran the experiment aboard an aircraft flying in parabolic arcs to specially simulate zero gravity conditions, to mimic the damage that can happen to the meniscus due to lack of exercise.

“Some of the genes that were found in the females that responded more to simulated space microgravity were also associated with the development of knee osteoarthritis,” said principal investigator Adetola Adesida, professor of surgery in the Faculty of Medicine & Dentistry.

The results suggest that a blood test could screen for the high-risk gene, allowing for early interventions such as physiotherapy, and eventually even drug therapy. It might also allow women to stay in space longer.

“We’ve uncovered the mechanisms that lead to this higher response, and we are hoping to develop drugs to target those pathways and block those responses,” Adesida said.

Previously thought to be rather unimportant, meniscus acts as a load distributor for the body’s full weight. However, it is now known that just a small tear in the meniscus, often from a sports injury, increases the risk of later osteoarthritis, even if the damaged tissue has been removed. On the other hand, lack of use can also lead to deconditioning of the meniscus and increase arthritis risk.

Knee osteoarthritis is the most common joint problem, affecting an estimated 250 million people worldwide, including 14% of females older than 60 and 10% of males in the same age group.

Prof Adesida’s team has developed bioengineered meniscus tissue grown from cells that have been removed from the damaged menisci of otherwise healthy individuals. The hope is one day to be able to replace damaged tissue through transplant, preventing the development of knee osteoarthritis.

For their experiment on sex differences, the team studied how the bioengineered tissue functioned while at rest and under mechanical loading and unloading conditions. For the loading, they used a device that exerted hydrostatic pressure on the cells. For the unloading, they put the cells into a bioreactor designed by NASA to fly aboard the zero-gravity aircraft.

“Our loading and unloading experiment mimics what we actually see in a clinical situation where the development of spaceflight microgravity-induced knee osteoarthritic changes is possible,” he said.

“This will help us to have human relevant models to study knee osteoarthritis in the future. And our research has both Earth benefits and space benefits.”

The study findings were published in Frontiers in Bioengineering and Biotechnology.

Source: University of Alberta

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