Study helps explain why motivation to learn declines with age

Research on mice suggests aging affects a brain circuit critical for learning to make some types of decisions

October 28, 2020

Science Daily/Massachusetts Institute of Technology

As people age, they often lose their motivation to learn new things or engage in everyday activities. In a study of mice, MIT neuroscientists have now identified a brain circuit that is critical for maintaining this kind of motivation.

This circuit is particularly important for learning to make decisions that require evaluating the cost and reward that come with a particular action. The researchers showed that they could boost older mice's motivation to engage in this type of learning by reactivating this circuit, and they could also decrease motivation by suppressing the circuit.

"As we age, it's harder to have a get-up-and-go attitude toward things," says Ann Graybiel, an Institute Professor at MIT and member of the McGovern Institute for Brain Research. "This get-up-and-go, or engagement, is important for our social well-being and for learning -- it's tough to learn if you aren't attending and engaged."

Graybiel is the senior author of the study, which appears today in Cell. The paper's lead authors are Alexander Friedman, a former MIT research scientist who is now an assistant professor at the University of Texas at El Paso, and Emily Hueske, an MIT research scientist.

Evaluating cost and benefit

The striatum is part of the basal ganglia -- a collection of brain centers linked to habit formation, control of voluntary movement, emotion, and addiction. For several decades, Graybiel's lab has been studying clusters of cells called striosomes, which are distributed throughout the striatum. Graybiel discovered striosomes many years ago, but their function had remained mysterious, in part because they are so small and deep within the brain that it is difficult to image them with functional magnetic resonance imaging (fMRI).

In recent years, Friedman, Graybiel, and colleagues including MIT research fellow Ken-ichi Amemori have discovered that striosomes play an important role in a type of decision-making known as approach-avoidance conflict. These decisions involve choosing whether to take the good with the bad -- or to avoid both -- when given options that have both positive and negative elements. An example of this kind of decision is having to choose whether to take a job that pays more but forces a move away from family and friends. Such decisions often provoke great anxiety.

In a related study, Graybiel's lab found that striosomes connect to cells of the substantia nigra, one of the brain's major dopamine-producing centers. These studies led the researchers to hypothesize that striosomes may be acting as a gatekeeper that absorbs sensory and emotional information coming from the cortex and integrates it to produce a decision on how to act. These actions can then be invigorated by the dopamine-producing cells.

The researchers later discovered that chronic stress has a major impact on this circuit and on this kind of emotional decision-making. In a 2017 study performed in rats and mice, they showed that stressed animals were far more likely to choose high-risk, high-payoff options, but that they could block this effect by manipulating the circuit.

In the new Cell study, the researchers set out to investigate what happens in striosomes as mice learn how to make these kinds of decisions. To do that, they measured and analyzed the activity of striosomes as mice learned to choose between positive and negative outcomes.

During the experiments, the mice heard two different tones, one of which was accompanied by a reward (sugar water), and another that was paired with a mildly aversive stimulus (bright light). The mice gradually learned that if they licked a spout more when they heard the first tone, they would get more of the sugar water, and if they licked less during the second, the light would not be as bright.

Learning to perform this kind of task requires assigning value to each cost and each reward. The researchers found that as the mice learned the task, striosomes showed higher activity than other parts of the striatum, and that this activity correlated with the mice's behavioral responses to both of the tones. This suggests that striosomes could be critical for assigning subjective value to a particular outcome.

"In order to survive, in order to do whatever you are doing, you constantly need to be able to learn. You need to learn what is good for you, and what is bad for you," Friedman says.

"A person, or this case a mouse, may value a reward so highly that the risk of experiencing a possible cost is overwhelmed, while another may wish to avoid the cost to the exclusion of all rewards. And these may result in reward-driven learning in some and cost-driven learning in others," Hueske says.

The researchers found that inhibitory neurons that relay signals from the prefrontal cortex help striosomes to enhance their signal-to-noise ratio, which helps to generate the strong signals that are seen when the mice evaluate a high-cost or high-reward option.

Loss of motivation

Next, the researchers found that in older mice (between 13 and 21 months, roughly equivalent to people in their 60s and older), the mice's engagement in learning this type of cost-benefit analysis went down. At the same time, their striosomal activity declined compared to that of younger mice. The researchers found a similar loss of motivation in a mouse model of Huntington's disease, a neurodegenerative disorder that affects the striatum and its striosomes.

When the researchers used genetically targeted drugs to boost activity in the striosomes, they found that the mice became more engaged in performance of the task. Conversely, suppressing striosomal activity led to disengagement.

In addition to normal age-related decline, many mental health disorders can skew the ability to evaluate the costs and rewards of an action, from anxiety and depression to conditions such as PTSD. For example, a depressed person may undervalue potentially rewarding experiences, while someone suffering from addiction may overvalue drugs but undervalue things like their job or their family.

The researchers are now working on possible drug treatments that could stimulate this circuit, and they suggest that training patients to enhance activity in this circuit through biofeedback could offer another potential way to improve their cost-benefit evaluations.

"If you could pinpoint a mechanism which is underlying the subjective evaluation of reward and cost, and use a modern technique that could manipulate it, either psychiatrically or with biofeedback, patients may be able to activate their circuits correctly," Friedman says.

https://www.sciencedaily.com/releases/2020/10/201028171435.htm

34% of older adults in the US are prescribed potentially inappropriate drugs

October 23, 2020

Science Daily/University at Buffalo

The prescription of potentially inappropriate medications to older adults is linked to increased hospitalizations, and it costs patients, on average, more than $450 per year, according to a new University at Buffalo study.

The research, which sought to determine the impact of potentially inappropriate medications on health care utilization and costs in the United States, also found that more than 34% of adults age 65 and older were prescribed these problematic drugs.

"Although efforts to de-prescribe have increased significantly over the last decade, potentially inappropriate medications continue to be prescribed at a high rate among older adults in the United States," says David Jacobs, PharmD, PhD, lead investigator and assistant professor of pharmacy practice in the UB School of Pharmacy and Pharmaceutical Sciences.

Collin Clark, PharmD, first author on the paper and clinical assistant professor in the School of Pharmacy and Pharmaceutical Sciences, adds, "The average age of the U.S. population is rising, and older adults account for a disproportionate amount of prescription medications. Harm to older adults caused by potentially inappropriate medications is a major public health challenge."

As the human body ages, the risk of experiencing harmful side effects from medications increases. Potentially inappropriate medications are drugs that should be avoided by older adults due to these risks outweighing the benefits of the medication, or when effective but lower risk alternative treatments are available.

The study, which was published in August in the Journal of the American Geriatrics Society, used the 2011-2015 Medical Expenditure Panel Survey -- conducted annually by the U.S. Public Health Service and the Centers for Disease Control and Prevention (CDC) -- to examine the prescription of 33 potentially inappropriate medications or classes of medications to adults 65 and older.

Among the potentially inappropriate medications examined were antidepressants, barbiturates, androgens, estrogens, nonsteroidal anti-inflammatory drugs, first-generation antihistamines, and antipsychotics.

Among the 218 million-plus older adults surveyed, more than 34% were prescribed at least one potentially inappropriate medication. Those patients were, on average, prescribed twice as many drugs, were nearly twice as likely to be hospitalized or visit the emergency department, and were more likely to visit a primary care physician compared to older adults who were not prescribed potentially inappropriate medication.

Patients who received these medications also spent an additional $458 on health care, including an extra $128 on prescription drugs.

"De-prescribing is currently at an early stage in the United States. Further work is needed to implement interventions that target unnecessary and inappropriate medications in older adults," says Jacobs.

https://www.sciencedaily.com/releases/2020/10/201023095850.htm

Exercise intensity not linked to mortality risk in older adults, finds trial

October 7, 2020

Science Daily/BMJ

Exercise intensity appears to make no difference to risk of mortality among older adults, suggests a randomised controlled trial from Norway published by The BMJ today.

Physical activity has been highlighted as one of the most important actions people of all ages can engage in to improve health, and data from observational studies show that early death is significantly reduced in physically active compared with inactive individuals.

Yet high quality clinical trial evidence on a potential direct (causal) relation between current advice on physical activity levels and longevity is lacking.

So an international research team set out to evaluate the effect of five years of supervised exercise training compared with recommendations for physical activity on mortality in older adults (70-77 years).

The trial involved 1,567 participants (790 women and 777 men) living in Trondheim, Norway, with an average age of 73 years. In total, 87.5% of participants reported overall good health and 80% reported a medium or high level of physical activity at the start of the trial.

Of these 1,567 participants, 400 were assigned to two weekly sessions of high intensity interval training (HIIT), 387 were assigned to moderate intensity continuous training (MICT), and 780 to follow the Norwegian guidelines for physical activity (control group), all for five years.

After five years, the overall mortality rate was 4.6% (72 participants).

The researchers found no difference in all cause mortality between the control group (4.7%, 37 participants) and combined HIIT and MICT group (4.5%, 35 participants).

They also found no differences in cardiovascular disease or cancer between the control group and the combined HIIT and MICT group.

For example, the total proportion of participants with cardiovascular disease after five years was 15.6%, with 16% (125 participants) in the control group, 15% (58 participants) in the MICT group, and 15.3% (61 participants) in the HIIT group.

The researchers point to some limitations. For example, highly active participants in the control group could have hampered finding differences between groups, and many participants were healthier than expected at the start of the study, which may have limited the potential to increase activity levels further.

However, strengths include the large number of older adults, and the long intervention period and monitoring throughout the study.

"This study suggests that combined MICT and HIIT has no effect on all cause mortality compared with recommended physical activity levels," write the researchers.

https://www.sciencedaily.com/releases/2020/10/201007193656.htm

Loneliness predicts development of type 2 diabetes

September 15, 2020

Science Daily/King's College London

Published in the journal Diabetologia (the journal of the European Association for the Study of Diabetes [EASD]), the study shows that it is the absence of quality connections with people and not the lack of contact that predicts the onset of type 2 diabetes, suggesting that helping people form and experience positive relationships could be a useful tool in prevention strategies for type 2 diabetes.

The results have implications in light of recent findings that people with diabetes are at greater risk of dying from COVID-19. The study indicates that prolonged loneliness may influence the development of diabetes, suggesting the experience of lockdown could potentially compound people's vulnerability in this pandemic if the loneliness continues for some time.

Loneliness occurs when an individual perceives that their social needs are not being met and reflects an imbalance between desired and actual social relationships. A fifth of adults in the UK and a third of adults in the USA report feeling lonely sometimes.

There is a growing interest in the role of loneliness in health and previous research has associated loneliness with increased risk of death and heart disease. This is the first study to investigate the experience of loneliness with later onset of type 2 diabetes.

The study analysed data from the English Longitudinal Study Ageing on 4112 adults aged 50 years and over which was collected at several times from 2002 to 2017. At the start of data collection all participants were free of diabetes and had normal levels of blood glucose.

The study showed that over a period of 12 years 264 people developed type 2 diabetes. and the level of loneliness measured at the start of data collection was a significant predictor of the onset of type 2 diabetes later on in life. This relationship remained intact when accounting for smoking, alcohol, weight, level of blood glucose, high blood pressure and cardiovascular disease. The association was also independent of depression, living alone and social isolation.

Lead author Dr Ruth Hackett from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) King's College London said: 'The study shows a strong relationship between loneliness and the later onset of type 2 diabetes. What is particularly striking is that this relationship is robust even when factors that are important in diabetes development are taken into account such as smoking, alcohol intake and blood glucose as well as mental health factors such as depression. The study also demonstrates a clear distinction between loneliness and social isolation in that isolation or living alone does not predict type 2 diabetes whereas loneliness, which is defined by a person's quality of relationships, does.

She continued: 'I came up with the idea for the research during UK lockdown for the COVID-19 pandemic as I became increasingly aware and interested in how loneliness may affect our health, especially as it is likely that many more people were experiencing this difficult emotion during this period.'

According to the study a possible biological reason behind the association between loneliness and type 2 diabetes could be the impact of constant loneliness on the biological system responsible for stress, which, over time affects the body and increases the risk for diabetes.

'If the feeling of loneliness becomes chronic,' explained Dr Hackett. 'Then everyday you're stimulating the stress system and over time that leads to wear and tear on your body and those negative changes in stress-related biology may be linked to type 2 diabetes development.'

Another explanation for the findings could be biases in our thinking that may perpetuate the association between loneliness and diabetes as when people feel lonely, they expect people will react to them negatively which makes it more difficult to form good relationships.

https://www.sciencedaily.com/releases/2020/09/200915105943.htm

Pain 'catastrophizing' may lead to little exercise, more time sedentary

August 27, 2020

Science Daily/Penn State

Chronic pain affects the majority of older adults in the U.S., and getting enough exercise plays a key role in pain management. New research suggests that how people think about their pain can have a significant effect on whether they get enough physical activity -- or if they spend more time sedentary.

In a study, a team led by Penn State researchers found that when people with knee osteoarthritis "catastrophized" -- feeling an exaggerated helplessness or hopelessness -- about their pain more than usual, they were less likely to be physically active later in the day, contributing to a domino effect of sedentary behavior followed by even more pain catastrophizing.

According to the researchers, the results -- recently published in the journal PAIN -- have potential implications for pain management and wellness in older adults, and suggest that pain catastrophizing could be an important therapeutic target for interventions and pain treatment.

"Reducing daily pain catastrophizing may help older patients to be more active and less sedentary on a daily basis," said Ruixue Zhaoyang, assistant research professor. "This could help improve their chronic pain condition, physical function, and overall health, and reduce the possibility of hospitalization, institutionalization, and healthcare costs in the long term."

According to the researchers, chronic or persistent pain affects between 60 and 75 percent of older adults in the U.S., making pain management strategies like engaging in enough physical activity an important part of many older adults' lives.

Zhaoyang said that catastrophizing about pain -- thought patterns like "the pain is terrible and is never going to get any better" or "I can't stand the pain anymore" -- may lead some older adults to avoid exercise in an effort to also avoid pain. But if exercise is put off for too long, it can lead to spirals of depression and even worse pain.

"Staying physically active is one of the most important self-management strategies for chronic pain patients," said Lynn Martire, professor of human development and family studies. "However, many chronic pain patients avoid physical activities that they are actually capable of doing. Our study focused on one critical psychological factor that may explain why patients avoid physical activity despite its importance for pain management: their catastrophic thinking about their pain."

For the study, the researchers used data from 143 older adults with knee osteoarthritis. The participants kept daily diaries and wore accelerometers -- a wearable device for measuring physical activity -- for 22 days. Each morning, the participants would report how they felt about their pain that day and the accelerometer would gather information on physical activity and sedentary behavior.

After analyzing the data, the researchers found that on mornings when participants catastrophized about their pain more than usual, they ended up engaging in less moderate to vigorous physical activity later that day.

Additionally, the researchers found that catastrophizing about pain in the morning lead to more time in sedentary behavior the same and the following day, as well. In turn, more time spent sedentary lead to increased pain catastrophizing on the following day.

"One particularly interesting finding is that the detrimental influence of catastrophizing thinking about pain is independent of the pain experience itself," Zhaoyang said. "In other words, how patients think about their pain, rather than the level of experienced pain, had a more powerful impact on their daily physical activity."

Martire said the results suggest that pain catastrophizing can kick-start a potentially harmful cycle -- greater pain catastrophizing in the morning leads to avoid of physical activity, which in turn worsens catastrophizing about pain on the following day.

The researchers added that these findings suggest that pain catastrophizing could be a good target for interventions aimed at managing chronic pain and increasing physical activity.

"Our study demonstrated that patients' catastrophizing thinking can change from day to day and can be modified by their everyday activity behavior," Martire said. "Future interventions may get better results from using mobile technology to monitor patients' activity levels in everyday life and provide just-in-time adaptive interventions targeting patients' pain catastrophizing to reduce their sedentary behavior."

The researchers added that while their study looked specifically at people with knee osteoarthritis, catastrophizing can happen with any type of pain. They said the implications of their findings could potentially apply to pain management in patients with other types of chronic pain.

https://www.sciencedaily.com/releases/2020/08/200825160549.htm

Older adults with existing depression show resilience during the pandemic

August 19, 2020

Science Daily/University of California - Los Angeles Health Sciences

A study involving older adults with pre-existing major depressive disorder living in Los Angeles, New York, Pittsburgh, and St Louis found no increase in depression and anxiety during the COVID-19 pandemic.

Researchers from five institutions, including UCLA, found that the older adults, who were already enrolled in ongoing studies of treatment resistant depression, also exhibited resilience to the stress of physical distancing and isolation. The findings were published in peer-reviewed journal, The American Journal of Geriatric Psychiatry.

"We thought they would be more vulnerable to the stress of COVID because they are, by CDC definition, the most vulnerable population," said Helen Lavretsky, MD, a professor-in-residence of psychiatry and biobehavioral sciences at the Jane and Terry Semel Institute for Neuroscience and Human Behavior at UCLA. "But what we learned is that older adults with depression can be resilient. They told use that coping with chronic depression taught them to be resilient"

For the study, researchers conducted interviews with the participants, all of whom were over the age of 60, with an average age of 69, during the first two months of the pandemic. Using two screening assessments of depression and anxiety, PHQ-9 and PROMIS, researchers found no changes in the participants' depression, anxiety or suicidality scores before and during the pandemic.

Researchers further determined that:

• Participants were more concerned about the risk of contracting the virus than the risks of isolation.

• While all maintained physical distance, most did not feel socially isolated and were using virtual technology to connect with friends and family.

• While they were coping, many participants said their quality of life was lower, and they worry their mental health will suffer with continued physical distancing.

• Participants were upset by the inadequate governmental response to the pandemic.

Based on the findings, the study authors wrote that policies and interventions to provide access to medical services and opportunities for social interaction are needed to help older adults maintain mental health and quality of life as the pandemic continues.

Lavretsky said many participants reported their quality of life to be lower, and they worried that their mental health will suffer with continued physical distancing. She said further research is needed to determine the impact of the pandemic over time.

She added that the findings offer takeaways for others while weathering the pandemic. "These older persons living with depression have been under stress for a longer time than many of the rest of us. We could draw upon their resilience and learn from it."

The study identified several self-care and coping strategies used by the participants, which included maintaining regular schedules; distracting themselves from negative emotions with hobbies, chores, work or exercise; and using mindfulness to focus on immediate surroundings and needs without thinking beyond the present.

The authors further emphasized that access to mental health care and support groups, and continued social interaction are needed to help older adults whether the pandemic.

https://www.sciencedaily.com/releases/2020/08/200819170223.htm

Vitamin D twice a day may keep vertigo away

August 5, 2020

Science Daily/American Academy of Neurology

Taking vitamin D and calcium twice a day may reduce your chances of getting vertigo again, according to a study published in the August 5, 2020, online issue of Neurology®, the medical journal of the American Academy of Neurology.

"Our study suggests that for people with benign paroxysmal positional vertigo, taking a supplement of vitamin D and calcium is a simple, low-risk way to prevent vertigo from recurring," said Ji-Soo Kim, M.D., Ph.D., of Seoul National University College of Medicine in Korea. "It is especially effective if you have low vitamin D levels to begin with."

Benign paroxysmal positional vertigo happens when a change in head position gives you a sudden spinning sensation. It's one of the most common types of vertigo. Treatment includes a doctor performing a series of head movements that shift particles in the ears that cause the vertigo, but the condition tends to recur frequently. About 86% of people with this form of vertigo find that it interrupts their daily life or causes them to miss days at work.

The study looked at 957 people in Korea with benign paroxysmal positional vertigo who were treated successfully with the head movements. The participants were separated into two groups, intervention and observation.

The 445 people in the intervention group had their vitamin D levels taken at the start of the study. The 348 people with vitamin D levels below 20 nanograms per milliliter (ng/mL) were started on supplements with 400 international units of vitamin D and 500 milligrams of calcium twice daily, while those with vitamin D levels equal to or greater than 20 ng/mL were not given supplements.

The 512 people in the observation group did not have their vitamin D levels monitored and they did not get supplements.

Those in the intervention group who took the supplements had a lower recurrence rate for vertigo episodes after an average of one year than those in the observation group. People taking supplements had an average recurrence rate of 0.83 times per person-year, compared to 1.10 times per person-year for those in the observation group, or a 24% reduction in the annual recurrence rate.

There appeared to be greater benefit for those who were more deficient in vitamin D at the start of the study. Those who started with vitamin D levels lower than 10 ng/mL saw a 45% reduction in annual recurrence rate, while those starting with vitamin D levels at 10 to 20 ng/mL saw only a 14% reduction. A total of 38% of the people in the interventional group had another episode of vertigo, compared to 47% of those in the observation group.

"Our results are exciting because so far, going to the doctor to have them perform head movements has been the main way we treat benign paroxysmal positional vertigo," said Kim. "Our study suggests an inexpensive, low-risk treatment like vitamin D and calcium tablets may be effective at preventing this common, and commonly recurring, disorder."

A limitation of the study is that a large number of participants did not complete the entire study, with more people assigned to take the supplements dropping out of the study than in the observation group.

https://www.sciencedaily.com/releases/2020/08/200805160933.htm

Two paths of aging: New insights on promoting healthspan

Master aging circuit identified

July 16, 2020

Science Daily/University of California - San Diego

Molecular biologists and bioengineers at the University of California San Diego have unraveled key mechanisms behind the mysteries of aging. They isolated two distinct paths that cells travel during aging and engineered a new way to genetically program these processes to extend lifespan.

The research is described July 17 in the journal Science.

Our lifespans as humans are determined by the aging of our individual cells. To understand whether different cells age at the same rate and by the same cause, the researchers studied aging in the budding yeast Saccharomyces cerevisiae, a tractable model for investigating mechanisms of aging, including the aging paths of skin and stem cells.

The scientists discovered that cells of the same genetic material and within the same environment can age in strikingly distinct ways, their fates unfolding through different molecular and cellular trajectories. Using microfluidics, computer modeling and other techniques, they found that about half of the cells age through a gradual decline in the stability of the nucleolus, a region of nuclear DNA where key components of protein-producing "factories" are synthesized. In contrast, the other half age due to dysfunction of their mitochondria, the energy production units of cells.

The cells embark upon either the nucleolar or mitochondrial path early in life, and follow this "aging route" throughout their entire lifespan through decline and death. At the heart of the controls the researchers found a master circuit that guides these aging processes.

"To understand how cells make these decisions, we identified the molecular processes underlying each aging route and the connections among them, revealing a molecular circuit that controls cell aging, analogous to electric circuits that control home appliances," said Nan Hao, senior author of the study and an associate professor in the Section of Molecular Biology, Division of Biological Sciences.

Having developed a new model of the aging landscape, Hao and his coauthors found they could manipulate and ultimately optimize the aging process. Computer simulations helped the researchers reprogram the master molecular circuit by modifying its DNA, allowing them to genetically create a novel aging route that features a dramatically extended lifespan.

"Our study raises the possibility of rationally designing gene or chemical-based therapies to reprogram how human cells age, with a goal of effectively delaying human aging and extending human healthspan," said Hao.

The researchers will now test their new model in more complex cells and organisms and eventually in human cells to seek similar aging routes. They also plan to test chemical techniques and evaluate how combinations of therapeutics and drug "cocktails" might guide pathways to longevity.

"Much of the work featured in this paper benefits from a strong interdisciplinary team that was assembled," said Biological Sciences Professor of Molecular Biology Lorraine Pillus, one of the study's coauthors. "One great aspect of the team is that we not only do the modeling but we then do the experimentation to determine whether the model is correct or not. These iterative processes are critical for the work that we are doing."

https://www.sciencedaily.com/releases/2020/07/200716144732.htm

Blood iron levels could be key to slowing aging

July 16, 2020

Science Daily/University of Edinburgh

Genes linked to ageing that could help explain why some people age at different rates to others have been identified by scientists.

The international study using genetic data from more than a million people suggests that maintaining healthy levels of iron in the blood could be a key to ageing better and living longer.

The findings could accelerate the development of drugs to reduce age-related diseases, extend healthy years of life and increase the chances of living to old age free of disease, the researchers say.

Scientists from the University of Edinburgh and the Max Planck Institute for Biology of Ageing in Germany focused on three measures linked to biological ageing -- lifespan, years of life lived free of disease (healthspan), and being extremely long-lived (longevity).

Biological ageing -- the rate at which our bodies decline over time -- varies between people and drives the world's most fatal diseases, including heart disease, dementia and cancers.

The researchers pooled information from three public datasets to enable an analysis in unprecedented detail. The combined dataset was equivalent to studying 1.75 million lifespans or more than 60,000 extremely long-lived people.

The team pinpointed ten regions of the genome linked to long lifespan, healthspan and longevity. They also found that gene sets linked to iron were overrepresented in their analysis of all three measures of ageing.

The researchers confirmed this using a statistical method -- known as Mendelian randomisation -- that suggested that genes involved in metabolising iron in the blood are partly responsible for a healthy long life.

Blood iron is affected by diet and abnormally high or low levels are linked to age-related conditions such as Parkinson's disease, liver disease and a decline in the body's ability to fight infection in older age.

The researchers say that designing a drug that could mimic the influence of genetic variation on iron metabolism could be a future step to overcome some of the effects of ageing, but caution that more work is required.

The study was funded by the Medical Research Council and is published in the journal Nature Communications.

Anonymised datasets linking genetic variation to healthspan, lifespan, and longevity were downloaded from the publically available Zenodo, Edinburgh DataShare and Longevity Genomics servers.

Dr Paul Timmers from the Usher Institute at the University of Edinburgh, said: "We are very excited by these findings as they strongly suggest that high levels of iron in the blood reduces our healthy years of life, and keeping these levels in check could prevent age-related damage. We speculate that our findings on iron metabolism might also start to explain why very high levels of iron-rich red meat in the diet has been linked to age-related conditions such as heart disease."

Dr Joris Deelen from the Max Planck Institute for Biology of Ageing in Germany, said: "Our ultimate aim is to discover how ageing is regulated and find ways to increase health during ageing. The ten regions of the genome we have discovered that are linked to lifespan, healthspan and longevity are all exciting candidates for further studies."

https://www.sciencedaily.com/releases/2020/07/200716101548.htm

New research highlights increased loneliness in over-70s during COVID-19 pandemic

July 15, 2020

Science Daily/Trinity College Dublin

A joint report published by researchers at the Irish Longitudinal Study on Ageing (TILDA) and ALONE examines issues of loneliness and social isolation in older adults. The report offers fresh insight into the experiences of those over 70 who were advised to 'cocoon' as part of public health measures to curtail the spread of the COVID-19 virus. New data from ALONE which documents increased feelings of loneliness, anxiety and isolation in older adults throughout the pandemic, is compared with experiences of loneliness and isolation in older adults before the COVID-19 outbreak.

Previous research into this area has shown that strong social ties may protect people from emotional distress, cognitive decline, and physical disability, while loneliness and social isolation can cause harm to physical and psychological wellbeing. Both loneliness and social isolation have been strongly associated with poorer quality of life and other measures of well-being.

The TILDA study offers unique insights into the health, habits and experiences of older adults living in Ireland through its longitudinal research, examining a variety of key areas that affect older adults such as physical and mental health as well as economic and social factors. Research from TILDA highlights the prevalence of loneliness and social isolation in its nationally representative survey of participants which gives clear insight into the experiences of older people.

What does TILDA's research show prior to the pandemic?

• Over 70% of TILDA participants reported that they never or rarely feel lonely; less than 25% feel lonely some of the time while just 5% reported feeling lonely often.

• Of those living alone, 31% are rarely lonely, 32% sometimes lonely and 37% often lonely.

• Of those living with others, 49% are least lonely, 30% sometimes and 21% often lonely.

• Researchers point out that most older adults are not often lonely and appear quite resilient, while data from ALONE's helpline suggest that the COVID-19 pandemic has taken a toll on older people.

The rise of loneliness in a pandemic

Measures introduced to curb the spread of the COVID-19 virus, including physical distancing, and self-isolation particularly affected those over 70 who were 'cocooning'; disrupting daily routines and social interactions with friends and family. Following the outbreak of the virus, ALONE's Support and Telephone Befriending service continued remotely with volunteers calling and sending regular texts to older people with health and well-being tips and practical supports. Almost 500 smartphones were distributed to older adults with limited means of social interaction. Following an increase in calls for support, ALONE established a dedicated phoneline to provide help and services to vulnerable older adults who may have needed them. Report data from ALONE highlights increased feelings of loneliness and isolation amongst older people during the COVID-19 pandemic.

What does ALONE's research show?

• The ALONE national support line has received 26,174 calls during the period: March 9th to July 5th, 2020.

• 55% of callers were from the over 70s, the cohort advised to 'cocoon'.

• 75% of callers to the helpline were living alone.

• There has been an increase in callers who are putting off medical treatment or examination, including after falls.

• ALONE has seen a rise in callers reporting negative emotions, including suicidal ideation during the pandemic.

• Callers have most often requested support for their physical health, befriending, and emotional and mental health needs.

The data highlights that public health measures such as social distancing and cocooning to curb the spread of the virus has increased levels of loneliness and social isolation in older people. This may have a negative effect on the well-being of older adults and suggests that public policies should be developed to ensure that these issues are addressed. Researchers suspect that current physical distancing and social isolation measures will be most keenly felt by those who rely on community or church-based social participation and engagement.

A future research project led by TILDA in collaboration with ALONE will investigate and document the impact of the COVID-19 pandemic on the health and general well-being of older adults.

Professor Rose Anne Kenny, Principal Investigator of TILDA said:

''This collaborative report between ALONE and TILDA offers a unique perspective into how older adults have been affected by the COVID-19 pandemic. TILDA research shows that most older adults are not often lonely and highlights the resilience of older adults as they adapt to an ever-changing world. The world has witnessed how older adults have been disproportionately affected by the pandemic. ALONE's research provides front- line evidence that shows the true toll public health measures have had on older people with increased feelings of loneliness, anxiety and isolation. The impact of the pandemic is now being studied in the TILDA cohort and will be reported later this year. This will more precisely inform the impact of COVID-19 on loneliness and social isolation, and areas for policy intervention.''

Sean Moynihan, Chief Executive Officer of ALONE said:

''ALONE's coordinated National Response to the COVID-19 pandemic allowed us to respond with immediacy to the concerns newly emerging, and existing issues being elevated from older people. We worked to keep all our services operative through adaptation of their structures. The presence of this virus in society has further solidified existing issues while further alienating some older people, as we have seen extensive increases in loneliness through the isolation experienced from cocooning. We established a loneliness taskforce to ensure we were putting provisions in place to safeguard older people, presently, and into the future. Society needs to understand that loneliness can happen to anyone and can damage both your physical and mental health. It is distressing and we want to work towards breaking down this stigma. As Ireland's ageing population continues to develop, we must remember that there are several thousands of older people behind every percentage."

https://www.sciencedaily.com/releases/2020/07/200715111451.htm