Super-agers show resistance to tau and amyloid accumulation

July 15, 2020

Science Daily/Society of Nuclear Medicine and Molecular Imaging

Super-agers, or individuals whose cognitive skills are above the norm even at an advanced age, have been found to have increased resistance to tau and amyloid proteins, according to research presented at the Society of Nuclear Medicine and Molecular Imaging (SNMMI) 2020 Annual Meeting. An analysis of positron emission tomography (PET) scans has shown that compared to normal-agers and those with mild cognitive impairment, super-agers have a lower burden of tau and amyloid pathology associated with neurodegeneration, which probably allows them to maintain their cognitive performance. An image showing the comparison of tau and amyloid distribution patterns in these different cognitive aging trajectories has been selected as SNMMI's 2020 Image of the Year.

"Our cognition reflects who we are as individuals. As we age, most of us lose some of that ability," said SNMMI's Scientific Program Committee chair, Umar Mahmood, MD, PhD. "The Image of the Year provides us with insight into how we can use these PET imaging biomarkers to understand behaviors and therapies that may allow more of us age better and retain more of our cognitive abilities as we get older."

Each year, SNMMI chooses an image that best exemplifies the most promising advances in the field of nuclear medicine and molecular imaging. The state-of-the-art technologies captured in these images demonstrate the capacity to improve patient care by detecting disease, aiding diagnosis, improving clinical confidence and providing a means of selecting appropriate treatments. This year, the SNMMI Henry N. Wagner, Jr., MD, Image of the Year was chosen from more than two thousand abstracts submitted to the meeting and voted on by reviewers and the society leadership.

"The phenomenon of super-aging suggests that cognitively high-functioning individuals have extraordinary mechanisms that resist brain aging processes and neurodegeneration," said Dr. Merle Hoenig, Research Center Juelich & University Hospital Cologne, Germany. Some insights have been collected on amyloid pathology in super-agers, but there is no in vivo evidence on tau pathology due to the former lack of available imaging techniques. "We know that tau pathology is more closely associated with cognitive decline than amyloid pathology," Hoenig continued, "thus, the resistance, in particular against tau pathology, likely allows these individuals to perform cognitively above average even at advanced age."

Data from the Alzheimer's Disease Neuroimaging Initiative was utilized to create three age- and education-matched groups of 25 super-agers, 25 normal-agers and 25 patients with mild cognitive impairment, all above 80 years old. In addition, 18 younger, cognitively normal, amyloid-negative controls were included in the comparison as a reference group. 18F-AV-1451 and 18F-AV-45 PET images obtained for all individuals and researchers compared the tau and amyloid burden between the four groups. A logistic regression was performed to identify genetic and pathophysiological factors best predicting aging processes.

No significant differences between super-agers and the younger control group were observed in terms of in vivo tau and amyloid burden. The normal-ager group exhibited tau burden in inferior temporal and precuneal areas and no significant differences in amyloid burden, when compared to the younger control group. Patients with mild cognitive impairment showed both high amyloid and high tau pathology burden. Differences in amyloid burden dissociated the normal-agers from those with mild cognitive impairment, whereas lower tau burden and lower polygenic risk predicted super-agers from mild cognitive impairment patients.

"While super-agers may be able to resist aging-associated proteinopathies, in particular tau pathology, normal-agers may not and are thus exposed to inevitable cognitive decline due to the accumulation of neurotoxic tau tangles and the advancing aging process," noted Hoenig. "Moving further to the other extreme of aging, namely mild cognitive impairment, the synergistic effects of both amyloid and tau may accelerate the pathological aging process."

These results motivate further research to determine responsible resistance factors, which may also inspire the development of novel treatment concepts. "Given the multitude of factors involved in the aging process, it will certainly be challenging to develop therapeutics to tackle the factors involved. However, if we understand which individuals are resistant to dementia, this will help us identify potential pathways that promote successful aging -- protecting against not only Alzheimer's disease but also other aging-associated diseases, such as vascular disease and other forms of dementia," said Hoenig.

https://www.sciencedaily.com/releases/2020/07/200715111447.htm

Why do arteries age? Study explores link to gut bacteria, diet

July 1, 2020

Science Daily/University of Colorado at Boulder

Eat a slab of steak and your resident gut bacteria get to work immediately to break it down. But new research shows that a metabolic byproduct, called TMAO, produced in the process can be harmful to the lining of arteries, making them age faster.

A compound produced in the gut when we eat red meat damages our arteries and may play a key role in boosting risk of heart disease as we get older, according to new University of Colorado Boulder research.

The study, published this month in the American Heart Association journal Hypertension, also suggests that people may be able to prevent or even reverse such age-related decline via dietary changes and targeted therapies, like novel nutritional supplements.

"Our work shows for the first time that not only is this compound directly impairing artery function, it may also help explain the damage to the cardiovascular system that naturally occurs with age," said first author Vienna Brunt, a postdoctoral researcher in the Department of Integrative Physiology.

Eat a slab of steak or a plate of scrambled eggs, and your resident gut bacteria get to work immediately to break it down. As they metabolize the amino acids L-carnitine and choline, they churn out a metabolic byproduct called trimethylamine, which the liver converts to trimethylamine-N-Oxide (TMAO) and sends coursing through your bloodstream.

Previous studies have shown that people with higher blood levels of TMAO are more than twice as likely to have a heart attack or stroke and tend to die earlier.

But to date, scientists haven't completely understood why.

Drawing on animal and human experiments, Brunt and her team set out to answer three questions: Does TMAO somehow damage our vascular system? If so, how? And could it be one reason why cardiovascular health gets worse -- even among people who exercise and don't smoke -- as we get older?

The researchers measured the blood and arterial health of 101 older adults and 22 young adults and found that TMAO levels significantly rise with age. (This falls in line with a previous study in mice, showing the gut microbiome -- or your collection of intestinal bacteria -- changes with age, breeding more bacteria that help produce TMAO).

Adults with higher blood levels of TMAO had significantly worse artery function, the new study found, and showed greater signs of oxidative stress, or tissue damage, in the lining of their blood vessels.

When the researchers fed TMAO directly to young mice, their blood vessels swiftly aged.

"Just putting it in their diet made them look like old mice," said Brunt. She noted that 12-month-old mice (the equivalent of humans about 35 years old) looked more like 27-month-old mice (age 80 in people) after eating TMAO for several months.

Preliminary data also show that mice with higher levels of TMAO exhibit decreases in learning and memory, suggesting the compound could also play a role in age-related cognitive decline.

On the flip side, old mice that ate a compound called dimethyl butanol, (found in trace amounts in olive oil, vinegar and red wine) saw their vascular dysfunction reverse. Scientists believe that this compound prevents the production of TMAO.

Brunt notes that everyone -- even a young vegan -- produces some TMAO. But over time, eating a lot of animal products may take a toll.

"The more red meat you eat, the more you are feeding those bacteria that produce it," she said.

Senior author Doug Seals, director of the Integrative Physiology of Aging Laboratory, said the study is an important breakthrough because it sheds light on why our arteries erode with age, even in the healthiest people.

"Aging is the single greatest risk factor for cardiovascular disease, primarily as a result of oxidative stress to our arteries," said Seals. "But what causes oxidative stress to develop in our arteries as we age? That has been the big unkown. This study identifies what could be a very important driver."

The research team is now further exploring compounds that might block production of TMAO to prevent age-related vascular decline.

For now, they said, a plant-based diet may also keep levels in check.

https://www.sciencedaily.com/releases/2020/07/200701100019.htm

Changes in the immune system can promote healthy aging

July 10, 2020

Science Daily/Max-Planck-Gesellschaft

As we age, the immune system gradually becomes impaired. One aspect of this impairment is chronic inflammation in the elderly, which means that the immune system is constantly active and sends out inflammatory substances. Such chronic inflammation is associated with multiple age-related diseases including arthritis and Alzheimer's disease, and impaired immune responses to infection. One of the questions in ageing research is whether chronic inflammation is a cause of ageing, or a consequence of the ageing process itself? Scientists in the laboratory of Director Adam Antebi at the Max Planck Institute for Biology of Ageing in Cologne, Germany have found evidence suggesting that increased inflammation causes the ageing process to speed up, and that there is a fine balance between maintaining immune system function and longevity.

From their work in the tiny roundworm, Caenorhabditis elegans, the scientists discovered a change in an evolutionarily conserved gene called PUF60, which made the worms long lived but at the same time dampened the immune response. Worms with this change lived about 20% longer than normal worms, but when they were infected with certain bacteria, they succumbed more quickly to the infection. This means that an overactive immune system also has a price: it shortens life span. Conversely, a less active immune system pays off as longer life span -- as long as the animal does not die from an infection.

How does PUF60 regulate this fine balance between a maintained immune system and longevity? PUF60 works as a so-called "splicing factor," and is involved in the removal (or "splicing out") of segments in the ribonucleic acid, RNA. This process is essential to generate functional proteins.

The scientists found that the genetically changed PUF60 perturbs this process and alters the regulation of other genes that are involved in immune functions. "We're excited by this finding because it implicates a very fundamental process in the cell to immunity," says Adam Antebi. "These observations of course raise further questions. Notably pinpointing how PUF60 activity affects immunity and longevity, and how these two processes are balanced will be central to understanding the relationship between inflammation and ageing."

https://www.sciencedaily.com/releases/2020/07/200710121810.htm

Among older adults, statin use tied to decreased risk of early death

July 7, 2020

Science Daily/Brigham and Women's Hospital

Study after study has shown that statins can prevent heart attacks, strokes and death in middle-aged adults. But in 28 major clinical trials of statins, only 2 percent of participants have been 75 years or older. This means that even though older adults are at greater risk of heart disease and death, there is scant data on whether statins should be prescribed for them. A new study led by investigators from Brigham and Women's Hospital and VA Boston Healthcare System leverages national data from the U.S. Veterans Health Administration Services and Centers for Medicare & Medicaid Services to shed new light on the role statins may play for older adults who have not yet experienced a heart attack, stroke or other cardiovascular event. In their retrospective analysis, the researchers found that the risk of dying from any cause was lower by 25 percent among veterans who were using statins compared to those who were not treated with statins. The risk of dying from a cardiovascular event, such as a heart attack or stroke, was lower by 20 percent. The team's results are published in JAMA.

"Based on these data, age is not a reason to not prescribe statins," said lead and corresponding author Ariela Orkaby, MD, MPH, a physician scientist at VA Boston Health Care System and in the Division of Aging at the Brigham . "Statins are commonly studied and prescribed for middle-aged adults but understudied in people over age 75. One of the most remarkable things about our results is that we found the benefit of statins held true regardless of whether a person was older or younger or had a condition such as dementia."

Orkaby and colleagues looked at data on veterans who used VA services between 2002 and 2012, were 75 years or older, and had not previously had a heart attack, stroke or other cardiovascular event. Of the more than 300,000 eligible veterans, the team identified more than 57,000 who began taking statins during this time. Using propensity scoring, the authors compared individuals who began taking statins to those who had the same likelihood of being prescribed a statin based on clinical characteristics but did not receive a prescription for the drug.

Overall, taking statins was significantly associated with lower risk of death from a cardiovascular event or death from any cause. And the benefits remained for veterans at advanced age, including those who were 90 years or older. Lower death rates extended to those with other conditions such as dementia -- individuals who have been excluded from previous studies. In secondary analyses, the team found that starting a statin was also significantly associated with a lower risk of cardiovascular events such as heart attacks and strokes. Orkaby notes that it was particularly intriguing to see a marked decline in rate of strokes among the study's black participants.

"There are many interesting leads to follow up on," said Orkaby, "but it's important to keep in mind that this is not a randomized, clinical trial. Instead, it's a retrospective analysis using real world data that helps us explore where the truth lies."

The study focused only on veterans, a predominantly white and male population, which may limit its generalizability, but the study's size made it possible to glean statistically meaningful information on underrepresented groups. During the study's timeframe, the most commonly prescribed statin was simvastatin, but currently, higher-dose and higher-intensity statins have become more frequently prescribed. While statins are generally well tolerated, many people report aches and pains as a side effect, which may lead some to stop taking the drug. The current study did not evaluate whether patients discontinued statin use.

Two randomized, clinical trials of statins among older adults are now underway with results from one of the studies expected later this year. Orkaby and colleagues plan to follow up on their study by exploring the effects of statin dosing and examining outcomes for sub-populations included in their analysis.

https://www.sciencedaily.com/releases/2020/07/200707113222.htm

Disrupted circadian rhythms linked to later Parkinson's diagnoses

Researchers probe brain's 24-hour biological clock for neurodegenerative risks

June 15, 2020

Science Daily/University of California - San Francisco

Older men who have a weak or irregular circadian rhythm guiding their daily cycles of rest and activity are more likely to later develop Parkinson's disease, according to a new study by scientists at the UC San Francisco Weill Institute for Neurosciences who analyzed 11 years of data for nearly 3,000 independently living older men.

The scientists said their discovery of the link between circadian rhythms and Parkinson's -- a disease characterized by loss of control over movement, balance and other brain functions -- suggests these circadian disruptions may reflect neurodegenerative disease processes already affecting the brain's internal clock well before a Parkinson's diagnosis, and that they could be considered an early warning sign of the disease.

"The strength of the circadian rhythm activity seems to have a really important effect on health and disease, particularly in aging. In this latest study we found that even small changes in circadian rhythm in older men were associated with a greater likelihood of getting Parkinson's down the line," said study senior author Kristine Yaffe, MD, the Roy and Marie Scola Endowed Chair and vice chair of the Department of Psychiatry at UCSF, a professor of psychiatry, neurology, and epidemiology and biostatistics, and a member of the UCSF Memory and Aging Center.

The results -- published June 15, 2020 in JAMA Neurology -- merit follow-up, according to the study authors, to investigate whether physiological changes set off by disruptions in circadian rhythms might themselves be a trigger for neurodegeneration, and whether strengthening these rhythms could lower risk for developing Parkinson's.

Parkinson's is the second most common neurodegenerative disorder after Alzheimer's disease. 500,000 individuals in the United States have been diagnosed with Parkinson's disease, and many with the disease are undiagnosed, according to the National Institute of Neurological Disorders and Stroke. Most who have Parkinson's are diagnosed after age 60. There are no drugs known to prevent the disease, but there are a growing number of treatments to relieve symptoms.

Among older adults, weakened or irregular circadian rhythms of rest and activity are common, according to study lead author Yue Leng, MD, PhD, an assistant professor of psychiatry at UCSF. Other conditions -- constipation or deficits in the sense of smell -- have also been associated with increased likelihood of developing Parkinson's later on.

"Parkinson's is a disease that probably takes decades to develop, and apart from changes in movement, earlier signs might be critical in understanding the disease and its mechanisms," Leng said. "This is the first large, long-term study to find that disrupted circadian rhythms might be linked to Parkinson's that emerges years later."

The study, which enrolled 2,930 men with an average age of 76.3 when the research began, was part of the larger, population-based Osteoporotic Fractures in Men Study (MRoS), which began in 2000 and enrolled men at six medical centers nationwide. None of the participants in the subset of the MRoS cohort initially had Parkinson's, and all were living in community-based settings (i.e. not in nursing homes). Their status for many health-related factors was assessed at the start, and they were monitored through follow-up visits and questionnaires.

As part of the study, researchers monitored circadian rhythms of rest and activity over three separate 24-hour periods by having participants wear an actigraph -- a watch-like device that detects and records even slight wrist movements. The data collected from these devices were independently associated with the later development of Parkinson's.

In a previous study, Leng and Yaffe identified an association between daytime napping and the later development of Parkinson's. But the link between circadian rhythms and Parkinson's is not just a matter or disrupted sleep, according to the new study. The association held true even after accounting for indicators of sleep disturbances -- including loss of sleep; sleep inefficiency (time spent asleep after turning off the lights); leg movement during sleep; and the chronic, temporary cessation of breathing known as sleep apnea.

In drawing this conclusion, the researchers took into account numerous other variables collected as part of the MRoS study, including regional differences in study sites and participant demographics, education, baseline cognitive performance, chronic diseases, physical activity, symptoms of depression, body mass index, smoking, and use of benzodiazepines, alcohol, and caffeine.

Leng and Yaffe evaluated four parameters of participants' rest-activity rhythms as measured by actigraph: amplitude, the difference between the period of greatest to least activity; mesor, the average activity; robustness, how well the measured cyclical rest-activity matched a regular curve similar to a cosine wave; and acrophase, a measure of advance or delay in the 24-hour cycle relative to the population average.

During follow-up, 78 of the 2,930 study participants were diagnosed with Parkinson's. Those who scored lowest in actigraph amplitude, mesor or robustness had triple the risk of developing Parkinson's compared to those who scored highest. The researchers did not find an association between acrophase and Parkinson's risk.

Animal models of Parkinson's have shown that cells controlling the brain's circadian rhythm pacemaker often begin to degenerate even before cells in the part of the brain that are traditionally associated with Parkinson's symptoms, suggesting that weakening of circadian rhythm may in some cases represent an early stage of disease.

Leng also does not rule out the possibility that disruptions in circadian rhythm, already known to cause metabolic changes and inflammation, might themselves contribute to neurodegenerative disease. Leng hopes to investigate whether weakened circadian rhythms trigger inflammation or the abnormal accumulation of proteins seen in affected brain tissue in both Parkinson's and Alzheimer's.

"These neurodegenerative diseases are not reversible," she said. "But if research points to sleep or circadian problems being risk factors for neurodegeneration prior to traditional symptoms, then we may be able to use that information for early detection and diagnosis, or we might be able to intervene in ways that prevent development of neurodegenerative loss of function."

https://www.sciencedaily.com/releases/2020/06/200615142802.htm

Cognition and gait speed often decline together

Mexican Americans at higher risk

May 5, 2020

Science Daily/University of Texas Health Science Center at San Antonio

Measures of cognition and gait speed largely paralleled each other in a San Antonio study of 370 participants that included 9½ years of follow-up. One-fifth of participants were classified into a cognitive and physical vulnerability group. Mexican American participants were almost four times more likely than European Americans to be in the cognitive and physical vulnerability group.

Do thinking and walking go hand in hand in determining the health course of senior adults? A study published by UT Health San Antonio researchers found that, indeed, the two functions often parallel each other in determining a person's health trajectory.

The researchers analyzed data from 370 participants in the San Antonio Longitudinal Study of Aging (SALSA) and found that they grouped into three distinct trajectories. These classifications were based on the participants' changes on a cognitive measure and a gait speed task over an average of 9½ years:

• Stable cognition and gait class (65.4% of the participants).

• Cognitive and physical vulnerability class (22.2%).

• Physical vulnerability class (12.4%).

"In our community-based sample of Mexican American and European American older adults aged 65 to 74 years old at baseline, the majority of individuals began the study with higher scores in both domains, cognition and gait speed. During follow-up, this group demonstrated resilience to age-related declines and continued to be functionally independent," said study senior author Helen Hazuda, Ph.D., professor in UT Health San Antonio's Long School of Medicine and the principal investigator of SALSA.

"In contrast, one-fifth of individuals began the study with lower scores in cognition and gait speed. They experienced deterioration in each domain during the follow-up period," Dr. Hazuda said.

The third group of individuals, termed the physical vulnerability class, demonstrated stable cognition throughout the study, but their gait speed slowed over time.

2 effects, 1 root?

Cognition was assessed using English or Spanish versions of the Folstein Mini-Mental State Examination, a 30-item tool that assesses orientation to time and place, attention, recall, language and other aspects. Gait speed was measured with a timed 10-foot walk.

"For most of the population we studied, changes in cognition and gait speed were parallel, which suggests shared mechanisms," said Mitzi M. Gonzales, Ph.D., lead author of the study and a neuropsychologist with the Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, which is part of UT Health San Antonio.

Cognition and gait speed may be altered by blood vessel disease, brain tissue insults, hormone regulation, and abnormal deposits of amyloid beta and tau proteins in the brain, Dr. Gonzales said. Amyloid beta and tau deposits are well-known indicators of Alzheimer's disease but may impact gait, too.

"Abnormal protein deposition promotes neurodegeneration and synaptic loss, which may induce dysfunction in brain regions governing cognition and gait," said study coauthor Sudha Seshadri, M.D., professor of neurology in the Long School of Medicine and director of the Biggs Institute. "Another possibility is damage to white matter in regions integral to both cognition and gait coordination."

Groundbreaking San Antonio research

SALSA investigators led by Dr. Hazuda launched the study in 1992 and completed the baseline examination in 1996. Follow-up examinations were conducted at 18-month intervals between 2000 and 2005.

Among the 370 participants in this new analysis, 182 were Mexican American and 188 were European American. The Mexican American participants were almost four times more likely than European Americans to be in the cognitive and physical vulnerability class, even after statistical adjustment for educational attainment, income and chronic medical conditions, Dr. Gonzales said.

Prevalence of a key risk factor in this group, diabetes, was significantly higher in Mexican Americans (23%) than in European Americans (7%). Diabetes was associated with a 4½ times higher likelihood of being part of the cognitive and physical vulnerability class.

Poor start, poor course

Individuals who entered the study with poorer cognition and slower gait speed went on to decline in both domains at an accelerated pace through the years of follow-up, Dr. Hazuda said.

"In this at-risk group, we observed steeper rates of decline over and above the low starting point," Dr. Hazuda said. "This suggests that preventive efforts should ideally target young and middle-aged adults in which there is still time to intervene to alter the trajectories."

Overall, individuals in the cognitive and physical vulnerability class and the physical vulnerability class had a five- to sevenfold increased risk of mortality in comparison to the stable cognition and gait class.

https://www.sciencedaily.com/releases/2020/05/200505121717.htm

How hearing loss in old age affects the brain

April 23, 2020

Science Daily/Ruhr-University Bochum

If your hearing deteriorates in old age, the risk of dementia and cognitive decline increases. So far, it hasn't been clear why. A team of neuroscientists has examined what happens in the brain when hearing gradually deteriorates: key areas of the brain are reorganized, and this affects memory.

Daniela Beckmann, Mirko Feldmann, Olena Shchyglo and Professor Denise Manahan-Vaughan from the Department of Neurophysiology of the Medical Faculty worked together for the study.

When sensory perception fades

The researchers studied the brain of mice that exhibit hereditary hearing loss, similar to age related hearing loss in humans. The scientists analysed the density of neurotransmitter receptors in the brain that are crucial for memory formation. They also researched the extent to which information storage in the brain's most important memory organ, the hippocampus, was affected.

Adaptability of the brain suffers

Memory is enabled by a process called synaptic plasticity. In the hippocampus, synaptic plasticity was chronically impaired by progressive hearing loss. The distribution and density of neurotransmitter receptors in sensory and memory regions of the brain also changed constantly. The stronger the hearing impairment, the poorer were both synaptic plasticity and memory ability.

"Our results provide new insights into the putative cause of the relationship between cognitive decline and age-related hearing loss in humans," said Denise Manahan-Vaughan. "We believe that the constant changes in neurotransmitter receptor expression caused by progressive hearing loss create shifting sands at the level of sensory information processing that prevent the hippocampus from working effectively," she adds.

https://www.sciencedaily.com/releases/2020/04/200423130446.htm

Middle age may be much more stressful now than in the '90s

May 7, 2020

Science Daily/Penn State

If life feels more stressful now than it did a few decades ago, you're not alone. Even before the novel coronavirus started sweeping the globe, a new study found that life may be more stressful now than it was in the 1990s.

A team of researchers led by Penn State found that across all ages, there was a slight increase in daily stress in the 2010s compared to the 1990s. But when researchers restricted the sample to people between the ages of 45 and 64, there was a sharp increase in daily stress.

"On average, people reported about 2 percent more stressors in the 2010s compared to people in the past," said David M. Almeida, professor of human development and family studies at Penn State. "That's around an additional week of stress a year. But what really surprised us is that people at mid-life reported a lot more stressors, about 19 percent more stress in 2010 than in 1990. And that translates to 64 more days of stress a year."

Almeida said the findings were part of a larger project aiming to discover whether health during the middle of Americans' lives has been changing over time.

"Certainly, when you talk to people, they seem to think that daily life is more hectic and less certain these days," Almeida said. "And so we wanted to actually collect that data and run the analyses to test some of those ideas."

For the study, the researchers used data collected from 1,499 adults in 1995 and 782 different adults in 2012. Almeida said the goal was to study two cohorts of people who were the same age at the time the data was collected but born in different decades. All study participants were interviewed daily for eight consecutive days.

During each daily interview, the researchers asked the participants about their stressful experiences throughout the previous 24 hours. For example, arguments with family or friends or feeling overwhelmed at home or work. The participants were also asked how severe their stress was and whether those stressors were likely to impact other areas of their lives.

"We were able to estimate not only how frequently people experienced stress, but also what those stressors mean to them," Almeida said. "For example, did this stress affect their finances or their plans for the future. And by having these two cohorts of people, we were able to compare daily stress processes in 1990 with daily stress processes in 2010."

After analyzing the data, the researchers found that participants reported significantly more daily stress and lower well-being in the 2010s compared to the 1990s. Additionally, participants reported a 27 percent increase in the belief that stress would affect their finances and a 17 percent increase in the belief that stress would affect their future plans.

Almeida said he was surprised not that people were more stressed now than in the 90s, but at the age group that was mainly affected.

"We thought that with the economic uncertainty, life might be more stressful for younger adults," Almeida said. "But we didn't see that. We saw more stress for people at mid-life. And maybe that's because they have children who are facing an uncertain job market while also responsible for their own parents. So it's this generational squeeze that's making stress more prevalent for people at mid-life."

Almeida said that while there used to be a stereotype about people experiencing a midlife crisis because of a fear of death and getting older, he suspects the study findings -- recently published in the journal American Psychologist -- suggest midlife distress may be due to different reasons.

"It may have to do with people at mid-life being responsible for a lot of people," Almeida said. "They're responsible for their children, oftentimes they're responsible for their parents, and they may also be responsible for employees at work. And with that responsibility comes more daily stress, and maybe that's happening more so now than in the past."

Additionally, Almeida said the added stress could partially be due to life "speeding up" due to technological advances. This could be particularly true during stressful times like the coronavirus pandemic, when tuning out the news can seem impossible.

"With people always on their smartphones, they have access to constant news and information that could be overwhelming," Almeida said.

Susan T. Charles, University of California, Irvine; Jacqueline Mogle, Penn State; Johanna Drewelies, Humboldt University Berlin; Carolyn M. Aldwin, Oregon State University; Avron Spiro III, Boston University Schools of Public Health and Medicine and Department of Veteran's Affairs; and Denis Gerstorf, Humboldt University Berlin and Penn State, also participated in this work.

https://www.sciencedaily.com/releases/2020/05/200507094745.htm

Community factors influence how long you'll live

March 10, 2020

Science Daily/Penn State

While lifestyle choices and genetics go a long way toward predicting longevity, a new study shows that certain community characteristics also play important roles. American communities with more fast food restaurants, a larger share of extraction industry-based jobs, or higher population density have shorter life expectancies, according to researchers from Penn State, West Virginia, and Michigan State Universities. Their findings can help communities identify and implement changes that may promote longer lifespans among their residents.

"American life expectancy recently declined for the first time in decades, and we wanted to explore the factors contributing to this decline. Because of regional variation in life expectancy, we knew community-level factors must matter," said Elizabeth Dobis, a postdoctoral scholar at the Penn State-based Northeast Regional Center for Rural Development (NERCRD), and lead author of the study. "By analyzing place-based factors alongside personal factors, we were able to draw several conclusions about which community characteristics contribute most strongly to this variation in life expectancy."

Life expectancy refers to the length of time a person born in a given year can expect to live. Dobis and her colleagues analyzed on a county-by-county basis how life expectancy in 2014 has changed from a 1980 baseline, using data from more than 3,000 U.S. counties.

They developed a statistical model to determine the relationship between a dozen community variables and each county's 2014 life expectancy, while controlling for personal variables that are known to be important, such as sex, race, education, single-parent status, obesity, and alcohol use.

The community variables they examined included health care access, population growth and density, fast food restaurants, healthy food access, employment by sector, urbanization, and social capital, which measures the networks and bonds providing social cohesion among residents. They looked at each variable in isolation while holding others constant, allowing them to determine which variables independently exert the strongest effect on life expectancy.

The researchers found that a county's 1980 life expectancy value strongly predicted variations in the 2014 value, but it didn't account for all of the variation.

"When we controlled for historical life expectancy, we found three additional community factors that each exert a significant negative effect -- a greater number of fast food restaurants, higher population density, and a greater share of jobs in mining, quarrying, and oil and gas extraction," Dobis said. "For example, for every one percentage point increase in the number of fast food restaurants in a county, life expectancy declined by .004 years for men and .006 years for women."

This represents a 15-20 days shorter life span for every man, woman and child in a community, for each 10 percentage point increase in fast food restaurants in a community -- or a 150-200 day shorter life span if the number of fast food restaurants were to double.

Similarly, a one percent increase in a county's share of jobs in the mining, quarrying, oil and gas sectors was found to decrease average life expectancy by .04 years for men (or 15 days) and .06 years (22 days) for women.

The research, which was published recently in Social Science and Medicine, also revealed several community factors that are positively related to life expectancy, including a growing population, good access to physicians, and a greater level of social cohesion.

"We were surprised by the strong positive contribution of social capital to life expectancy within communities," said NERCRD Director Stephan Goetz, professor of agricultural economics and regional economics at Penn State and a co-author on the study. "Places with residents who stick together more on a community or social level also appear to do a better of job of helping people in general live longer."

"Another interesting finding was that lower population density, or living in more rural areas, is associated with higher life expectancy," Goetz said. "This suggests that living in large, densely-settled metropolitan areas, with all of their amenities and other advantages, comes at the expense of lower life expectancy, at least in a statistical sense."

In addition to being the first life-expectancy study to include community variables in a county-level analysis, this also was the first study to statistically analyze the extent to which disparities in life expectancy are geographically clustered. This analysis revealed some striking patterns.

"We found exceptionally low life expectancies in the areas of the Pine Ridge and Rosebud Reservations in South Dakota," Dobis said. "We found similar 'cold spots' of low life expectancy in the arctic and interior portions of Alaska, the Deep South surrounding the Mississippi River, and in the Appalachian regions of Kentucky and West Virginia."

The research also revealed four "hot spots" of high life expectancy: a section of the Northeast spanning from Philadelphia to New England, southern Minnesota and the eastern Dakotas into Nebraska, an area in Colorado, and an area spanning central Idaho into the upper Rocky Mountains.

The team's findings have important policy implications, as they suggest that certain aspects of the built environment can be changed to enhance life expectancy. For example, public places that promote social interaction could increase a community's social capital levels, which in turn promote longer lifespans.

https://www.sciencedaily.com/releases/2020/03/200310124706.htm

For older adults, more physical activity could mean longer, healthier lives

March 5, 2020

Science Daily/American Heart Association

Older adults were 67% less likely to die of any cause if they were moderately or vigorously physically active for at least 150 minutes per week, compared to people who exercised less. Women with an average age of 79 who walked 2,100 to 4,500 steps daily reduced their risk of dying from heart attacks, heart failure, stroke and other cardiovascular diseases by up to 38%, compared to women who walked less than 2,100 daily steps.

Two studies demonstrate that older adults may be able to live longer, healthier lives by increasing physical activity that doesn't have to be strenuous to be effective, according to preliminary research presented at the American Heart Association's Epidemiology and Prevention | Lifestyle and Cardiometabolic Health Scientific Sessions 2020. The EPI Scientific Sessions, March 3-6 in Phoenix, is a premier global exchange of the latest advances in population-based cardiovascular science for researchers and clinicians.

"Finding a way to physically move more in an activity that suits your capabilities and is pleasurable is extremely important for all people, and especially for older people who may have risk factors for cardiovascular diseases. Physical activities such as brisk walking can help manage high blood pressure and high cholesterol, improve glucose control among many benefits," said Barry A. Franklin, Ph.D., past chair of both the American Heart Association's Council on Physical Activity and Metabolism and the National Advocacy Committee, director of preventive cardiology and cardiac rehabilitation at Beaumont Health in Royal Oak, Michigan and professor of internal medicine at Oakland University William Beaumont School of Medicine in Rochester, Michigan.

Higher levels of light physical activity are associated with lower risk of death from any cause

Older adults were 67% less likely to die of any cause if they spent at least 150 minutes per week in moderate to vigorous physical activity -- a goal recommended by the American Heart Association -- compared to those who did not engage in more than 150 minutes per week of moderate to vigorous physical activity.

However, this investigation observed that, among the participants with an average age of 69, physical activity doesn't have to be strenuous to be effective. The researchers observed that each 30-minute interval of light-intensity physical activities -- such as doing household chores or casual walking -- was associated with a 20% lower risk of dying from any cause. Conversely, every additional 30-minutes of being sedentary was related to a 32% higher risk of dying from any cause.

"Promoting light-intensity physical activity and reducing sedentary time may be a more practical alternative among older adults," said Joowon Lee, Ph.D., a researcher at Boston University in Boston.

This investigation evaluated physical activity levels of 1,262 participants from the ongoing Framingham Offspring Study. Participants were an average age of 69 (54% women), and they were instructed to wear a device that objectively measured physical activity for at least 10 hours a day, for at least four days a week between 2011 and 2014.

The strengths of this investigation include its large sample size and the use of a wearable device to objectively measure physical activity. However, the participants of the Framingham Offspring Study are white, so it is unclear if these findings would be consistent for other racial groups.

Co-authors of the study are Nicole L. Spartano, Ph.D.; Ramachandran S. Vasan, M.D. and Vanessa Xanthakis Ph.D. Author disclosures are in the abstract.

This study was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health.

Every step counts in reducing cardiovascular disease deaths among older women

Women who walked 2,100 to 4,500 steps daily reduced their risk of dying from heart attacks, heart failure, stroke and other cardiovascular diseases by up to 38%, compared to women who walked less than 2,100 daily steps. The women who walked more than 4,500 steps per day reduced their risk by 48%, in this study of over 6,000 women with an average age of 79. 2

The cardio-protective effect of more steps per day was present even after the researchers took into consideration heart disease risk factors, such as obesity, elevated cholesterol, blood pressure, triglycerides and/or blood sugar levels, and was not dependent on how fast the women walked.4

"Despite popular beliefs, there is little evidence that people need to aim for 10,000 steps daily to get cardiovascular benefits from walking. Our study showed that getting just over 4,500 steps per day is strongly associated with reduced risk of dying from cardiovascular disease in older women," said lead study author Andrea Z. LaCroix, Ph.D., distinguished professor and chief of epidemiology at the University of California, San Diego.

"Taking more steps per day, even just a few more, is achievable, and step counts are an easy-to-understand way to measure how much we are moving. There are many inexpensive wearable devices to choose from. Our research shows that older women reduce their risk of heart disease by moving more in their daily life, including light activity and taking more steps. Being up and about, instead of sitting, is good for your heart," said LaCroix.

The study included more than 6,000 women enrolled in the Women's Health Initiative with an average age of 79 who wore an accelerometer on their waist to measure physical activity for seven days in a row; participants were followed for up to seven years for heart disease death.

This study was prospective, and half of the participants were African American or Hispanic. The use of an accelerometer to measure movement is a strength of the study. The study did not include men or people younger than 60, so it will be important for future research to examine step counts and other measures of daily activity across the adult age range among both men and women.

https://www.sciencedaily.com/releases/2020/03/200305132217.htm

Low blood pressure linked to high mortality in older adults

March 7, 2020

Science Daily/University of Exeter

A large-scale study analyzed 415,980 electronic medical records of older adults in England. People aged 75 or over with low blood pressure (below 130/80) had increased mortality rates in the follow-up, compared to those with normal blood pressure. This was especially pronounced in 'frail' individuals, who had 62% increased risk of death during the 10-year follow-up.

The research was conducted after some countries have changed blood pressure guidelines to encourage clinicians to take measures to reduce blood pressure in a bid to improve health outcomes. UK blood pressure guidelines are within safe parameters for all. However, previous research has not considered the impact on frail older adults, who are often omitted from trials.

The team found that people aged 75 or over with low blood pressure (below 130 / 80) had increased mortality rates in the follow-up, compared to those with normal blood pressure. This was especially pronounced in 'frail' individuals, who had 62 per cent increased risk of death during the ten year follow-up.

Although high blood pressure increased risk of cardiovascular incidents, such as heart attacks, it was not linked to higher mortality in frail adults over 75. Older people aged 85 and over who had raised blood pressure actually had reduced mortality rates, compared to those with lower blood pressure, regardless of whether they were frail or not.

Jane Masoli, a geriatrician and NIHR Doctoral Research Fellow, who led the study as part of her PhD at the University of Exeter, said: "Internationally, guidelines are moving towards tight blood pressure targets, but our findings indicate that this may not be appropriate in frail older adults. We need more research to ascertain whether aggressive blood pressure control is safe in older adults, and then for which patient groups there may be benefit, so we can move towards more personalised blood pressure management in older adults."

She added: "We know that treating blood pressure helps to prevent strokes and heart attacks and we would not advise anyone to stop taking their medications unless guided by their doctor."

https://www.sciencedaily.com/releases/2020/03/200307170735.htm

Keep exercising: New study finds it's good for your brain's gray matter

January 2, 2020

Science Daily/Mayo Clinic

A study provides new evidence of an association between cardiorespiratory fitness and brain health, particularly in gray matter and total brain volume -- regions of the brain involved with cognitive decline and aging.

Cardiorespiratory exercise -- walking briskly, running, biking and just about any other exercise that gets your heart pumping -- is good for your body, but can it also slow cognitive changes in your brain?

A study in Mayo Clinic Proceedings from the German Center for Neurodegenerative Diseases provides new evidence of an association between cardiorespiratory fitness and brain health, particularly in gray matter and total brain volume -- regions of the brain involved with cognitive decline and aging.

Brain tissue is made up of gray matter, or cell bodies, and filaments, called white matter, that extend from the cells. The volume of gray matter appears to correlate with various skills and cognitive abilities. The researchers found that increases in peak oxygen uptake were strongly associated with increased gray matter volume.

The study involved 2,013 adults from two independent cohorts in northeastern Germany. Participants were examined in phases from 1997 through 2012. Cardiorespiratory fitness was measured using peak oxygen uptake and other standards while participants used an exercise bike. MRI brain data also were analyzed.

The results suggest cardiorespiratory exercise may contribute to improved brain health and decelerate a decline in gray matter. An editorial by three Mayo Clinic experts that accompanies the Mayo Clinic Proceedings study says the results are "encouraging, intriguing and contribute to the growing literature relating to exercise and brain health."

Ronald Petersen, M.D., Ph.D., a Mayo Clinic neurologist and first author of the editorial, says the most striking feature of the study is the measured effect of exercise on brain structures involved in cognition, rather than motor function. "This provides indirect evidence that aerobic exercise can have a positive impact on cognitive function in addition to physical conditioning," he says. "Another important feature of the study is that these results may apply to older adults, as well. There is good evidence for the value of exercise in midlife, but it is encouraging that there can be positive effects on the brain in later life as well."

Dr. Petersen is the Cora Kanow Professor of Alzheimer's Disease Research and the Chester and Debbie Cadieux Director of the Mayo Clinic Alzheimer's Disease Research Center.

The study's finding of higher gray matter volume associated with cardiorespiratory exercise are in brain regions clinically relevant for cognitive changes in aging, including some involved in Alzheimer's disease. The editorial calls those associations interesting but cautions against concluding that cardiorespiratory fitness correlations would affect Alzheimer's disease.

"This is another piece of the puzzle showing physical activity and physical fitness is protective against aging-related cognitive decline," says Michael Joyner, M.D., a Mayo Clinic anesthesiologist and physiologist, and editorial co-author. "There's already good epidemiological evidence for this, as well as emerging data showing that physical activity and fitness are associated with improved brain blood vessel function. This paper is important because of the volumetric data showing an effect on brain structure."

Dr. Joyner is the Frank R. and Shari Caywood Professor at Mayo Clinic.

Long-term studies on the relationship between exercise and brain health are needed, which will be costly and logistically challenging to produce. "Nevertheless, these data are encouraging," says Clifford Jack Jr., M.D., a Mayo Clinic neuroradiologist and co-author of the editorial. "The findings regarding cardiorespiratory fitness and certain brain structures are unique."

Dr. Jack is the Alexander Family Professor of Alzheimer's Disease Research.

According to Mayo Clinic experts, moderate and regular exercise -- about 150 minutes per week -- is recommended. Good cardiorespiratory fitness also involves:

Not smoking

Following healthy eating habits

Losing weight or maintaining a healthy weight level

Managing blood pressure and avoiding hypertension

Controlling cholesterol levels

Reducing blood sugar, which over time can damage your heart and other organs

University Medicine Greifswald, Germany, also was part of the research project. Katharina Wittfeld, Ph.D., a researcher at the German Center for Neurodegenerative Disease, is first author.

https://www.sciencedaily.com/releases/2020/01/200102094314.htm

Solving a biological puzzle: How stress causes gray hair

Scientists uncover link between the nervous system and stem cells that regenerate pigment

January 22, 2020

Science Daily/Harvard University

Scientists have found evidence to support long-standing anecdotes that stress causes hair graying. Researchers found that in mice, the type of nerve involved in the fight-or-flight response causes permanent damage to the pigment-regenerating stem cells in the hair follicle. The findings advance knowledge of how stress impacts the body, and are a first step toward blocking its negative effects.

When Marie Antoinette was captured during the French Revolution, her hair reportedly turned white overnight. In more recent history, John McCain experienced severe injuries as a prisoner of war during the Vietnam War -- and lost color in his hair.

For a long time, anecdotes have connected stressful experiences with the phenomenon of hair graying. Now, for the first time, Harvard University scientists have discovered exactly how the process plays out: stress activates nerves that are part of the fight-or-flight response, which in turn cause permanent damage to pigment-regenerating stem cells in hair follicles.

The study, published in Nature, advances scientists' knowledge of how stress can impact the body.

"Everyone has an anecdote to share about how stress affects their body, particularly in their skin and hair -- the only tissues we can see from the outside," said senior author Ya-Chieh Hsu, the Alvin and Esta Star Associate Professor of Stem Cell and Regenerative Biology at Harvard. "We wanted to understand if this connection is true, and if so, how stress leads to changes in diverse tissues. Hair pigmentation is such an accessible and tractable system to start with -- and besides, we were genuinely curious to see if stress indeed leads to hair graying. "

Narrowing down the culprit

Because stress affects the whole body, researchers first had to narrow down which body system was responsible for connecting stress to hair color. The team first hypothesized that stress causes an immune attack on pigment-producing cells. However, when mice lacking immune cells still showed hair graying, researchers turned to the hormone cortisol. But once more, it was a dead end.

"Stress always elevates levels of the hormone cortisol in the body, so we thought that cortisol might play a role," Hsu said. "But surprisingly, when we removed the adrenal gland from the mice so that they couldn't produce cortisol-like hormones, their hair still turned gray under stress."

After systematically eliminating different possibilities, researchers honed in on the sympathetic nerve system, which is responsible for the body's fight-or-flight response.

Sympathetic nerves branch out into each hair follicle on the skin. The researchers found that stress causes these nerves to release the chemical norepinephrine, which gets taken up by nearby pigment-regenerating stem cells.

Permanent damage

In the hair follicle, certain stem cells act as a reservoir of pigment-producing cells. When hair regenerates, some of the stem cells convert into pigment-producing cells that color the hair.

Researchers found that the norepinephrine from sympathetic nerves causes the stem cells to activate excessively. The stem cells all convert into pigment-producing cells, prematurely depleting the reservoir.

"When we started to study this, I expected that stress was bad for the body -- but the detrimental impact of stress that we discovered was beyond what I imagined," Hsu said. "After just a few days, all of the pigment-regenerating stem cells were lost. Once they're gone, you can't regenerate pigment anymore. The damage is permanent."

The finding underscores the negative side effects of an otherwise protective evolutionary response, the researchers said.

"Acute stress, particularly the fight-or-flight response, has been traditionally viewed to be beneficial for an animal's survival. But in this case, acute stress causes permanent depletion of stem cells," said postdoctoral fellow Bing Zhang, the lead author of the study.

Answering a fundamental question

To connect stress with hair graying, the researchers started with a whole-body response and progressively zoomed into individual organ systems, cell-to-cell interaction and, eventually, all the way down to molecular dynamics. The process required a variety of research tools along the way, including methods to manipulate organs, nerves, and cell receptors.

"To go from the highest level to the smallest detail, we collaborated with many scientists across a wide range of disciplines, using a combination of different approaches to solve a very fundamental biological question," Zhang said.

The collaborators included Isaac Chiu, assistant professor of immunology at Harvard Medical School who studies the interplay between nervous and immune systems.

"We know that peripheral neurons powerfully regulate organ function, blood vessels, and immunity, but less is known about how they regulate stem cells," Chiu said.

"With this study, we now know that neurons can control stem cells and their function, and can explain how they interact at the cellular and molecular level to link stress with hair graying."

The findings can help illuminate the broader effects of stress on various organs and tissues. This understanding will pave the way for new studies that seek to modify or block the damaging effects of stress.

"By understanding precisely how stress affects stem cells that regenerate pigment, we've laid the groundwork for understanding how stress affects other tissues and organs in the body," Hsu said. "Understanding how our tissues change under stress is the first critical step towards eventual treatment that can halt or revert the detrimental impact of stress. We still have a lot to learn in this area."

https://www.sciencedaily.com/releases/2020/01/200122135313.htm

What it's like to live without a sense of smell

January 22, 2020

Science Daily/University of East Anglia

New research reveals the impact of smell loss. As many as one in 20 people live without smell. But until now there has been little research into the range of emotional and practical impacts it causes. The new study finds that almost every aspect of life is disrupted - from everyday concerns about personal hygiene to a loss of sexual intimacy and the break-down of personal relationships.

The smell of cut grass, freshly baked bread, childhood memories, lost loved ones, Christmas. What happens when it's all gone?

A new study from the University of East Anglia reveals the huge range of emotional and practical impacts caused by a loss of smell.

It finds that almost every aspect of life is disrupted -- from everyday concerns about personal hygiene to a loss of sexual intimacy and the break-down of personal relationships.

The researchers hope that their findings will help motivate clinicians to take smell problems more seriously, with better help and support offered to patients.

Prof Carl Philpott, from UEA's Norwich Medical School, said: "Smell disorders affect around five per cent of the population and cause people to lose their sense of smell, or change the way they perceive odours. Some people perceive smells that aren't there at all.

"There are many causes -- from infections and injury to neurological diseases such as Alzheimer's and as a side effect of some medications.

"Most patients suffer a loss of flavour perception which can affect appetite and can be made even worse if distortions in their sense of smell also co-exist.

"Previous research has shown that people who have lost their sense of smell also report high rates of depression, anxiety, isolation and relationship difficulties.

"We wanted to find out more about how a loss of smell affects people."

The researchers worked with the Smell and Taste clinic at the James Paget University Hospital, Gorleston-On-Sea. The clinic opened in 2010 and was the UK's first clinic dedicated to taste and smell.

The study involved 71 participants aged between 31-80 who had written to the clinic about their experiences. It was carried out in collaboration with Fifth Sense, the charity for people affected by smell and taste disorders.

The research shows that sufferers experience wide-ranging impairments to their quality of life. These included a negative emotional impact, feelings of isolation, impaired relationships and daily functioning, impacts on physical health and the difficulty and financial burden of seeking help.

Prof Philpot said: "One really big problem was around hazard perception -- not being able to smell food that had gone off, or not being able to smell gas or smoke. This had resulted in serious near misses for some.

"But smell is not just a life-saving sense -- it is also life-enhancing.

"A large number of the participants no longer enjoyed eating, and some had lost appetite and weight. Others were eating more food with low nutritional value that was high in fat, salt and sugar -- and had consequently gained weight.

"Participants had lost interest in preparing food and some said they were too embarrassed to serve dishes to family and friends which had an impact on their social lives.

"The inability to link smells to happy memories was also a problem. Bonfire night, Christmas smells, perfumes and people -- all gone. Smells link us to people, places and emotional experiences. And people who have lost their sense of smell miss out on all those memories that smell can evoke.

"We found that personal hygiene was a big cause for anxiety and embarrassment, because the participants couldn't smell themselves.

"Parents of young children couldn't tell when their nappies needed changing, and this led to feelings of failure. One mother found it difficult bonding with her new baby because she couldn't smell him.

"Many participants described a negative impact on relationships -- ranging from not enjoying eating together to an impact on sexual relationships," he added.

All of these problems led to diverse range of negative emotions including anger, anxiety, frustration, depression, isolation, loss of confidence, regret and sadness. And the problems were compounded by a lack of understanding about the disorder among clinicians.

Prof Philpott said: "The participants described a lot of negative and unhelpful interactions with healthcare professionals before coming to the James Paget Smell and Taste clinic. Those that did manage to get help and support were very pleased -- even if nothing could be done about their condition, they were very grateful for advice and understanding."

Duncan Boak, Founder and Chair of Fifth Sense, said: "Anosmia can have a huge impact on people's quality of life in many ways, as this research demonstrates. An important part of Fifth Sense's work is giving our beneficiaries a voice and the opportunity to change the way society understands smell and taste disorders, whether through volunteering or participating in research studies like this one. The results of this study will be a big help in our ongoing work to improve the lives of those affected by anosmia."

https://www.sciencedaily.com/releases/2020/01/200122175643.htm

Lonely in a crowd: Overcoming loneliness with acceptance and wisdom

Study looked at characteristics of loneliness in a senior housing community and the strategies residents used to overcome it

January 10, 2020

Science Daily/University of California - San Diego

Researchers found the main characteristics of loneliness in a senior housing community and the strategies residents use to overcome it.

By nature, human beings are social creatures. Yet, as we age, personal dynamics and lifestyles change, which can result in loneliness and isolation. With older adults increasingly moving into senior living or retirement communities, researchers at University of California San Diego School of Medicine sought to identify the common characteristics of residents who feel lonely in these environments.

"Loneliness rivals smoking and obesity in its impact on shortening longevity," said senior author Dilip V. Jeste, MD, senior associate dean for the Center of Healthy Aging and Distinguished Professor of Psychiatry and Neurosciences at UC San Diego School of Medicine. "It is a growing public health concern, and it's important that we identify the underlying causes of loneliness from the seniors' own perspectives so we can help resolve it and improve the overall health, well-being and longevity of our aging population."

Jeste noted that there are few published qualitative studies about loneliness among older adults in the independent living sector of senior housing communities, where shared common areas, planned social outings and communal activities are intended to promote socialization and reduce isolation. "So why are many older adults living in this type of housing still experiencing strong feelings of loneliness?" asked Jeste.

The new study, published online in the January 10, 2020 issue of Aging and Mental Health, found that people's experience of living with loneliness is shaped by a number of personal and environmental factors.

Researchers conducted one-and-a-half-hour individual interviews of 30 adults ages 67 to 92, part of an overall study evaluating the physical, mental and cognitive functions of 100 older adults living in the independent living sector of a senior housing community in San Diego.

In this communal setting, 85 percent of the residents reported moderate to severe levels of loneliness. "Loneliness is subjective," said Jeste. "Different people feel lonely for different reasons despite having opportunities and resources for socialization. This is not a one size fits all topic."

Three main themes emerged from the study:

• Age-associated losses and inadequate social skills were considered to be primary risk factors for loneliness. "Some residents talked about the loss of spouses, siblings and friends as the cause of their loneliness. Others mentioned how making new friends in a senior community cannot replace deceased friends they grew up with," said first author Alejandra Paredes, PhD, a research fellow in the Department of Psychiatry at UC San Diego School of Medicine.

• The feeling of loneliness was frequently associated with a lack of purpose in life. "We heard powerful comments like, 'It's kind of gray and incarcerating,'" said Jeste. "Others expressed a sense of 'not being attached, not having very much meaning and not feeling very hopeful' or 'being lost and not having control.'"

• The research team also found that wisdom, including compassion, seemed to be a factor that prevented loneliness. "One participant spoke of a technique she had used for years, saying 'if you're feeling lonely, then go out and do something for somebody else.' That's proactive," said Jeste. Other protective factors were acceptance of aging and comfort with being alone. "One resident told us, 'I've accepted the aging process. I'm not afraid of it. I used to climb mountains. I want to keep moving, even if I have to crawl. I have to be realistic about getting older, but I consider and accept life as a transition,'" Jeste noted. "Another resident responded, 'I may feel alone, but that doesn't mean I'm lonely. I'm proud I can live by myself.'"

According to the National Center for Health Statistics, by 2029, more than 20 percent of the United States population will be over the age of 65. "It is paramount that we address the well-being of our seniors -- they are friends, parents and grandparents of the younger generations," said Jeste. "Our study is relevant to better understand loneliness within senior housing and other settings to so we can develop effective interventions."

https://www.sciencedaily.com/releases/2020/01/200110101033.htm

Brain waves in mice change based on memory age

December 17, 2019

Science Daily/RIKEN

Researchers have discovered signatures in brain activity that allow them to tell old and new memories apart. The team analyzed recordings from mouse brains using a machine-leaning algorithm, which was able to accurately classify memories as recent or remote. They also found robust communication between a frontal brain region and the hippocampus, a link which may form a concrete mechanism that tracks the age of memories.

Identifying the location and persistence of memories in the brain has implications for cases of brain damage, memory loss, and clinical memory impairment. In this study, the researchers were interested in how different brain areas that contain memory traces interact, especially during memory recall. The anterior cingulate cortex (ACC) in the prefrontal brain is known to be anatomically connected to the hippocampus. The team wanted to study this connection more closely, at the level of signals from individual neurons.

They recorded activity in both brain areas before exposing mice to a memory-forming experience (a foot shock), and then again in the same cage both one day and one month later. If mice froze in the same context, it was a behavioral indication that they remembered the shock. But the neuronal recordings also revealed that the ACC and hippocampus, specifically area CA1, are highly synchronized when mice recall the fear memory.

The interactions of the two brain areas changed over time, with ACC and CA1 activity becoming more correlated when an old or 'remote' memory was recalled compared to the recent, one-day memory. Specific frequencies and modes of neural activity became more pronounced between the two areas when the mice recalled the older memory, with the ACC appearing to drive activity in hippocampus in a top-down manner. "While memory is consolidated over time in frontal areas, we think in this case the ACC is facilitating the retrieval of contextual details back from the hippocampus," said senior author and team leader Thomas McHugh of RIKEN CBS.

The evolving pattern of signals over time allowed the researchers to distinguish old and new memories in mice from the brain recordings alone. "We could decode whether a mouse was recalling a recent or remote memory by looking at the correlations in ACC-CA1 interactions," said McHugh. Moreover, the researchers suggest that a small group of CA1 neurons carries the information about memory age.

"While we have known for 20 years that the ACC is important for recalling older memories, how it contributes has remained a mystery" McHugh explained. "We found that it plays in important role in organizing activity in the hippocampus, the part of the brain in which the memory was originally formed. This suggests the hippocampus always plays a role in providing key details of an old experience, at least in the healthy brain."

The team is now focused on understanding how impairments in long-term memory that often accompany aging and disease impacts activity in these brain circuits.

https://www.sciencedaily.com/releases/2019/12/191217114229.htm

Hydration may affect cognitive function in some older adults

December 12, 2019

Science Daily/Penn State

Among women, lower hydration levels were associated with lower scores on a task designed to measure motor speed, sustained attention, and working memory. They did not find the same result for men.

 Not getting enough water is enough to make you feel sluggish and give you a headache, but a new Penn State study suggests it may also relate to cognitive performance.

The researchers investigated whether hydration levels and water intake among older adults was related with their scores on several tests designed to measure cognitive function. They found that among women, lower hydration levels were associated with lower scores on a task designed to measure motor speed, sustained attention, and working memory. They did not find the same result for men.

The findings were recently published in the European Journal of Nutrition.

"The study gives us clues about how hydration and related drinking habits relate to cognition in older adults," said Hilary Bethancourt, a postdoctoral scholar in biobehavioral health and first author on the study. "This is important because older adults already face increased risk of cognitive decline with advancing age and are often less likely than younger adults to meet daily recommendations on water intake."

Asher Rosinger, Ann Atherton Hertzler Early Career Professor in Global Health, said the researchers found similar results when the participants were overhydrated.

"We found a trend suggesting overhydration may be just as detrimental to cognitive performance as dehydration for older adults," said Rosinger, who also directs the Water, Health, and Nutrition Laboratory and was senior author on the study. "Because of this, being in the 'sweet spot' of hydration seems to be best for cognitive function, especially for tasks requiring sustained attention."

According to the researchers, scientists have long suspected that dehydration may have an effect on cognitive performance. However, previous studies have largely focused on young, healthy people who are dehydrated after exercise and/or being in the heat.

Bethancourt said that because exercise and elevated ambient and body temperatures can have their own, independent effects on cognition, she and the other researchers were interested in the effects of day-to-day hydration status in the absence of exercise or heat stress, especially among older adults.

"As we age, our water reserves decline due to reductions in muscle mass, our kidneys become less effective at retaining water, and hormonal signals that trigger thirst and motivate water intake become blunted," Bethancourt said. "Therefore, we felt like it was particularly important to look at cognitive performance in relation to hydration status and water intake among older adults, who may be underhydrated on a regular basis."

For the study, the researchers used data from a nationally representative sample of 1271 women and 1235 men who were 60 years of age or older. Data were collected by the Nutrition and Health Examination Survey. Participants gave blood samples and were asked about all foods and drinks consumed the previous day. The researchers calculated hydration status based on concentrations of sodium, potassium, glucose, and urea nitrogen in participants' blood. Total water intake was measured as the combined liquid and moisture from all beverages and foods.

Participants also completed three tasks designed to measure different aspects of cognition, with the first two measuring verbal recall and verbal fluency, respectively.

A final task measured processing speed, sustained attention, and working memory. Participants were given a list of symbols, each matched with a number between one and nine. They were then given a list of numbers one through nine in random order and asked to draw the corresponding symbol for as many numbers as possible within two minutes.

Bethancourt said that when they first plotted the average test scores across different levels of hydration status and water intake, there appeared to be a distinct trend toward higher test scores in relation to adequate hydration and/or meeting recommended water intake. However, much of that was explained by other factors.

"Once we accounted for age, education, hours of sleep, physical activity level, and diabetes status and analyzed the data separately for men and women, the associations with hydration status and water intake were diminished," Bethancourt said. "A trend toward lower scores on the number-symbol test among women who were categorized as either underhydrated or overhydrated was the most prominent finding that remained after we accounted for other influential factors."

Bethancourt said that because the data was cross-sectional, they can't be sure whether suboptimal hydration levels are causing cognitive impairment or if people with impaired cognition are just more likely to be under- or overhydrated. The researchers were also unsure why they failed to see the same associations among men. Still, she said the results raise interesting questions.

"It was interesting that even though the test of attention, processing speed, and working memory took only a few minutes, it was the one most strongly associated with lower hydration levels," Bethancourt said. "Other research has similarly suggested that attention may be one of the cognitive domains most affected by hydration status. This left us wondering what the effects of inadequate hydration might be on more difficult tasks requiring longer periods of concentration and focus."

Rosinger said the findings suggest older adults may want to pay close attention to their hydration status, by both consuming enough liquids to avoid dehydration as well as ensuring adequate electrolyte balance to avoid overhydration.

"Because older adults may not necessarily feel thirsty when their body is reaching a state of underhydration and may be taking diuretics that can increase salt excretion, it is important for older adults and their physicians to better understand the symptoms of being both under- and overhydrated," said Rosinger.

https://www.sciencedaily.com/releases/2019/12/191212142720.htm

'Loneliness epidemic' may be due to increasing aging population

December 10, 2019

Science Daily/American Psychological Association

Despite some claims that Americans are in the midst of a 'loneliness epidemic,' older people today may not be any lonelier than their counterparts from previous generations -- there just might be more of them, according to a pair of new studies.

Despite some claims that Americans are in the midst of a "loneliness epidemic," older people today may not be any lonelier than their counterparts from previous generations -- there just might be more of them, according to a pair of studies published by the American Psychological Association.

"We found no evidence that older adults have become any lonelier than those of a similar age were a decade before," said Louise C. Hawkley, PhD, of NORC at the University of Chicago, lead author of one of the studies. "However, average reported loneliness begins to increase beyond age 75, and therefore, the total number of older adults who are lonely may increase once the baby boomers reach their late 70s and 80s."

The studies were published in the journal Psychology and Aging.

Hawkley and her colleagues used data from the National Social Life, Health and Aging Project and the Health and Retirement Study, two national surveys of older adults that compared three groups of U.S. adults born in different periods throughout the 20th century. They first analyzed data in 2005 to 2006 from 3,005 adults born between 1920 and 1947 and a second time in 2010 to 2011 from 3,377 people, which included those from the previous survey who were still alive, and their spouses or partners. The third survey, in 2015 to 2016, comprised 4,777 adults, which included an additional sample of adults born between 1948 and 1965 to the surviving respondents from the previous two surveys.

The authors examined participants' level of loneliness, educational attainment, overall health on a scale from poor to excellent, marital status and number of family members, relatives and friends they felt close to. They found that loneliness decreased between the ages of 50 and 74, but increased after age 75, yet there was no difference in loneliness between baby boomers and similar-aged adults of earlier generations.

"Loneliness levels may have decreased for adults between 50 and 74 because they had better educational opportunities, health care and social relationships than previous generations," said Hawkley.

Adults over 75 were more susceptible to becoming lonely, possibly due to life factors such as declining health or the loss of a spouse or significant other, according to Hawkley.

"Our research suggests that older adults who remain in good health and maintain social relationships with a spouse, family or friends tend to be less lonely," said Hawkley.

In a similar study, researchers in the Netherlands found that older adults were less lonely than their counterparts from previous generations.

These researchers used data from the Longitudinal Aging Study Amsterdam, a long-term study of the social, physical, cognitive and emotional functioning of older adults. A total of 4,880 people, born between 1908 and 1957, participated.

The study measured peoples' loneliness, control over situations and life in general and goal achievement. For example, participants rated loneliness on a scale from 0 (no loneliness) to 11 (severe loneliness) based on feelings such as, "I miss having people around."

Older adults born in later generations were actually less lonely, because they felt more in control and thus most likely managed their lives better, according to Bianca Suanet, PhD, of Vrije Universiteit Amsterdam and lead author of the study.

"In contrast to assuming a loneliness epidemic exists, we found that older adults who felt more in control and therefore managed certain aspects of their lives well, such as maintaining a positive attitude, and set goals, such as going to the gym, were less lonely," said Suanet. "Additionally, as is well-known in loneliness research, participants who had a significant other and/or larger and more diverse networks were also less lonely."

Suanet recommended that older adults take personal initiative to better nurture their social ties, such as making friends to help them overcome increasing loneliness as they age. Also, interventions to reduce loneliness should focus more on bolstering older adults' feelings of control, instead of only offering social activities.

"People must manage their social lives better today than ever before because traditional communities, which provided social outlets, such as neighborhoods, churches and extended families, have lost strength in recent decades," said Suanet. "Therefore, older adults today need to develop problem-solving and goal-setting skills to sustain satisfying relationships and to reduce loneliness."

Seniors may also want to make use of modern technology to maintain meaningful social connections, according to Hawkley.

"Video chatting platforms and the Internet may help preserve their social relationships," said Hawkley. "These tools can help older adults stay mobile and engaged in their communities."

https://www.sciencedaily.com/releases/2019/12/191210111711.htm

A blood factor involved in weight loss and aging

October 22, 2019

Science Daily/Institut Pasteur

Aging can be delayed through lifestyle changes (physical exercise, restricting calorie intake, etc.). Researchers have elucidated the properties of a molecule in the blood - GDF11 - whose mechanisms were previously unknown. In a mouse model, they showed that this molecule could mimic the benefits of certain calorie restrictions - dietary regimens that have proven their efficacy in reducing cardiovascular disease, preventing cancer and increasing neurogenesis in the brain.

Aging is a process that affects all functions of the human body, particularly brain function. However, aging can be delayed through lifestyle changes (physical exercise, restricting calorie intake, etc.). Researchers at the Institut Pasteur and CNRS have elucidated the properties of a molecule in the blood -- GDF11 -- whose mechanisms were previously unknown. In a mouse model, they showed that this molecule could mimic the benefits of certain calorie restrictions -- dietary regimens that have proven their efficacy in reducing cardiovascular disease, preventing cancer and increasing neurogenesis in the brain. The results of this research were published in the journal Aging Cell on October 22, 2019.

Today it is possible to maintain a healthy brain in the long term. For the past 30 years, it has been generally acknowledged that certain diet restrictions such as intermittent fasting can improve cognitive performance and extend life expectancy in several species. It has also been proven that calorie restriction (a reduction in calorie intake of 20% to 30% while preserving nutritional quality) reduces the risk of cardiovascular disease and cancer, while increasing production of new neurons in the brain.

In a previous study using mouse models, scientists observed that injecting aged mice with blood from young mice rejuvenated blood vessels in the brain, and consequently improved cerebral blood flow, while increasing neurogenesis and cognition . Scientists in the Perception and Memory Unit (Institut Pasteur/CNRS) put forward the theory that, since calorie restriction and supplementation with young blood were effective in rejuvenating organs, they most likely have certain mechanisms in common.

They therefore examined the molecule GDF11, which belongs to the GDF (Growth Differentiation Factor) protein family and is involved in embryonic development. GDF11 was already known to scientists for its ability to rejuvenate the aged brain. "By injecting this molecule into aged mouse models, we noticed an increase in neurogenesis and blood vessel remodeling," explains Lida Katsimpardi, a scientist in the Perception and Memory Unit and lead author of the study. The scientists also observed that the mice administered with GDF11 had lost weight without changing their appetite. This observation led them to believe that GDF11 could be a link between calorie restriction and the regenerating effects of young blood.

The next step was to confirm this theory by studying adiponectin, a hormone secreted by adipose tissue which induces weight loss without affecting appetite. In animals that have undergone calorie restriction, the blood levels of this hormone are high. "In animals that were administered GDF11, we also observed high levels of adiponectin," emphasizes Lida Katsimpardi, "and this shows that GDF11 causes metabolic changes similar to those induced by calorie restriction."

Until recently, there has been controversy over the role of GDF11 in aging, and its mechanisms were largely unknown. The findings of this study show that by inducing phenomena similar to those reported for calorie restriction leading to the stimulation of adiponectin and neurogenesis, GDF11 contributes to the birth of new neurons in the brain. "These findings are encouraging and support therapeutic uses of GDF11 in certain metabolic diseases, such as obesity, and neurodegenerative diseases," concludes Pierre-Marie Lledo, CNRS researcher, Head of the Institut Pasteur's Perception and Memory Unit and last author of the study.

https://www.sciencedaily.com/releases/2019/10/191022104858.htm

The effects of obesity mirror those of aging

Researchers identify a shared list of health issues, from DNA damage to cognitive decline

February 25, 2020

Science Daily/Concordia University

Researchers argue that obesity should be considered premature aging. They look at how obesity predisposes people to acquiring the kinds of potentially life-altering or life-threatening diseases normally seen in older individuals: compromised genomes, weakened immune systems, decreased cognition, increased chances of developing type 2 diabetes, Alzheimer's disease, cardiovascular disease, cancer and other illnesses.

Globally, an estimated 1.9 billion adults and 380 million children are overweight or obese. According to the World Health Organization, more people are dying from being overweight than underweight. Researchers at Concordia are urging health authorities to rethink their approach to obesity.

In their paper published in the journal Obesity Reviews, the researchers argue that obesity should be considered premature aging. They look at how obesity predisposes people to acquiring the kinds of potentially life-altering or life-threatening diseases normally seen in older individuals: compromised genomes, weakened immune systems, decreased cognition, increased chances of developing type 2 diabetes, Alzheimer's disease, cardiovascular disease, cancer and other illnesses.

The study was led by Sylvia Santosa, associate professor of health, kinesiology and applied physiology in the Faculty of Arts and Science. She and her colleagues reviewed more than 200 papers that looked at obesity's effects, from the level of the cell to tissue to the entire body. The study was co-authored by Bjorn Tam, Horizon postdoctoral fellow, and José Morais, an associate professor in the Department of Medicine at McGill University.

"We are trying to comprehensively make the argument that obesity parallels aging," explains Santosa, a Tier II Canada Research Chair in Clinical Nutrition. "Indeed, the mechanisms by which the comorbidities of obesity and aging develop are very similar."

From cells to systems

The paper looks at ways obesity ages the body from several different perspectives. Many previous studies have already linked obesity to premature death. But the researchers note that at the lowest levels inside the human body, obesity is a factor that directly accelerates the mechanisms of aging.

For instance, Santosa and her colleagues look at the processes of cell death and the maintenance of healthy cells -- apoptosis and autophagy, respectively -- that are usually associated with aging.

Studies have shown that obesity-induced apoptosis has been seen in mice hearts, livers, kidneys, neurons, inner ears and retinas. Obesity also inhibits autophagy, which can lead to cancer, cardiovascular disease, type 2 diabetes and Alzheimer's.

At the genetic level, the researchers write that obesity influences a number of alterations associated with aging. These include the shortening of protective caps found on the ends of chromosomes, called telomeres. Telomeres in patients with obesity can be more than 25 per cent shorter than those seen in control patients, for instance.

Santosa and her colleagues further point out that obesity's effects on cognitive decline, mobility, hypertension and stress are all similar to those of aging.

Pulling out from the cellular level, the researchers say obesity plays a significant role in the body's fight against age-related diseases. Obesity, they write, speeds up the aging of the immune system by targeting different immune cells, and that later weight reduction will not always reverse the process.

The effects of obesity on the immune system, in turn, affect susceptibility to diseases like influenza, which often affects patients with obesity at a higher rate than normal-weight individuals. They are also at higher risk of sarcopenia, a disease usually associated with aging that features a progressive decline in muscle mass and strength.

Finally, the paper spells out how individuals with obesity are more susceptible to diseases closely associated with later-life onset, such as type 2 diabetes, Alzheimer's and various forms of cancer.

Similarities too big to ignore

Santosa says the inspiration for this study came to her when she realized how many children with obesity were developing adult-onset conditions of diseases, such as hypertension, high cholesterol and type 2 diabetes. She also realized that the comorbidities of obesity were similar to that of aging.

"I ask people to list as many comorbidities of obesity as they can," Santosa says. "Then I ask how many of those comorbidities are associated with aging. Most people will say, all of them. There is certainly something that is happening in obesity that is accelerating our aging process.'"

She thinks this research will help people better understand how obesity works and stimulate ideas on how to treat it.

"I'm hoping that these observations will focus our approach to understanding obesity a little more, and at the same time allow us to think of obesity in different ways. We're asking different types of questions than that which have traditionally been asked."

https://www.sciencedaily.com/releases/2020/02/200225122954.htm