TAG: "Geriatrics"

PTSD linked to accelerated aging

UC San Diego study is first of its type to link PTSD with aging.

By Scott LaFee and Heather Buschman, UC San Diego

In recent years, public health concerns about post-traumatic stress disorder (PTSD) have risen significantly, driven in part by affected military veterans returning from conflicts in the Middle East and elsewhere. PTSD is associated with number of psychological maladies, among them chronic depression, anger, insomnia, eating disorders and substance abuse.

Writing in today’s (May 7) online issue of American Journal of Geriatric Psychiatry, researchers at the UC San Diego School of Medicine and Veterans Affairs San Diego Healthcare System suggest that people with PTSD may also be at risk for accelerated aging or premature senescence.

“This is the first study of its type to link PTSD, a psychological disorder with no established genetic basis, which is caused by external, traumatic stress, with long-term, systemic effects on a basic biological process such as aging,” said Dilip V. Jeste, M.D., Distinguished Professor of Psychiatry and Neurosciences and director of the Center on Healthy Aging and Senior Care at UC San Diego, who is the senior author of this study.

Researchers had previously noted a potential association between psychiatric conditions, such as schizophrenia and bipolar disorder, and acceleration of the aging process. Jeste and colleagues determined to see if PTSD might show a similar association by conducting a comprehensive review of published empirical studies relevant to early aging in PTSD, covering multiple databases going back to 2000.

There is no standardized definition of what constitutes premature or accelerated senescence. For guidance, the researchers looked at early aging phenomena associated with non-psychiatric conditions, such as Hutchinson-Gilford progeria syndrome, HIV infection and Down syndrome. The majority of evidence fell into three categories: biological indicators or biomarkers, such as leukocyte telomere length (LTL), earlier occurrence or higher prevalence of medical conditions associated with advanced age and premature mortality.

In their literature review, the UC San Diego team identified 64 relevant studies; 22 were suitable for calculating overall effect sizes for biomarkers, 10 for mortality.

All six studies looking specifically at LTL found reduced telomere length in persons with PTSD. Leukocytes are white blood cells. Telomeres are stretches of protective, repetitive nucleotide sequences at the ends of chromosomes. These sequences shorten with every cell replication and are considered a strong measure of the aging process in cells.

The scientists also found consistent evidence of increased pro-inflammatory markers, such as C-reactive protein and tumor necrosis factor alpha, associated with PTSD.

A majority of reviewed studies found increased medical comorbidity of PTSD with several targeted conditions associated with normal aging, including cardiovascular disease, type 2 diabetes, gastrointestinal ulcer disease and dementia.

Seven of 10 studies indicated a mild-to-moderate association of PTSD with earlier mortality, consistent with an early onset or acceleration of aging in PTSD.

“These findings do not speak to whether accelerated aging is specific to PTSD, but they do argue the need to re-conceptualize PTSD as something more than a mental illness,” said first author James B. Lohr, M.D., professor of psychiatry. “Early senescence, increased medical morbidity and premature mortality in PTSD have implications in health care beyond simply treating PTSD symptoms. Our findings warrant a deeper look at this phenomenon and a more integrated medical-psychiatric approach to their care.”

Barton Palmer, Ph.D., professor of psychiatry and a coauthor of the study, cautioned that “prospective longitudinal studies are needed to directly demonstrate accelerated aging in PTSD and to establish underlying mechanisms.”

Other co-authors include Carolyn A. Eidt, Smitha Aailaboyina, and Steven R. Thorp, Veterans Affairs San Diego Healthcare System Center of Excellence for Stress and Mental Health and UCSD Department of Psychiatry and Stein Institute for Research on Aging; Brent T. Mausbach, UCSD Department of Psychiatry and Stein Institute for Research on Aging; and Owen M. Wolkowitz, UC San Francisco.

Funding for this research came, in part, from the Veterans Affairs San Diego Healthcare System Center of Excellence for Stress and Mental Health, National Institutes of Health grants R01MH099987, R01MH094151, T32MH019935, and U.S. Department of Defense, UC San Diego Center for Healthy Aging and Sam and Rose Stein Institute for Research on Aging.

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Japanese Americans’ healthier golden years could be model for other seniors

‘Japanese Americans provide a window into our future.’

By Venetia Lai, UCLA

Nearly 1 in 4 Japanese Americans are 65 and older — nearly twice the proportion of seniors in the overall U.S. population. The facts that they are likelier to live longer than other Americans and are healthier when they age make Japanese Americans an important subject of research by health policy experts — and could provide clues about how all Americans can age, according to a new study by the UCLA Center for Health Policy Research.

Using California Health Interview Survey data from 2003 to 2012, the study found that elderly Japanese Americans had lower risks for nine of 15 health indicators than other Asian and other racial and ethnic groups in California. Older Japanese Americans, however, did have higher rates of arthritis and hypertension than seniors in other racial and ethnic groups.

“Japanese Americans provide a window into our future,” said Ying-Ying Meng, lead author of the study and co-director of the center’s Chronic Disease Program. “They show us one vision of how our nation can age and can help us prepare for the enormous generational shift ahead.”

The report, which was funded by Keiro Senior HealthCare, examines three categories of Japanese in California: Those who identify as being “only” Japanese — typically with parents who both were Japanese; those who identify as being mixed race; and those who identified as being Japanese in some way.

Among the findings:

Japanese only

  • 2 in 5 have hypertension, compared with 1 in 5 Asians in California overall and 1 in 3 Californians.
  • 2 in 5 have arthritis, compared with 1 in 5 or fewer among Chinese, Korean and South Asians in the state.
  • About 9 percent have diabetes — higher than the 7 percent target set for all Californians by Let’s Get Healthy California, a state-backed initiative that sets health goals, but comparable to the prevalence among all California adults and Asians in the state overall.

Mixed race

  • 1 in 5 eat fast food four or more times a week, compared with 1 in 10 Japanese only.
  • About 8 percent have hypertension — significantly lower than the figure among the Japanese-only cohort (22 percent). The study’s authors say the disparity may be a result of the multiracial group being younger overall.

Any Japanese identification

  • About 1 in 3 reported binge drinking — significantly more than those in Chinese or Vietnamese communities (both fewer than 1 in 5).
  • About 9 percent have diabetes, the same as among the Japanese-only group.
  • About 14 percent are obese, nearly double the 6 percent rate among the Chinese community but close to the Let’s Get Healthy California goal of 11 percent, and much lower than the rate for Latinos (30 percent) and African-Americans (35 percent).
  • They are much less likely to self-report fair or poor overall health than all other Asian groups in California, except for South Asians.
  • Rates of serious psychological distress are low, although the authors say Japanese-American families might not report mental health needs because of stigma.
  • Japanese seniors had a much lower prevalence of falls, about 8 percent, than Latinos (15 percent) and whites (14 percent).

Japanese-only residents, in large part the older generation, have some health behaviors and health outcomes that outshine their racially mixed grandchildren.

“In diet, for instance, the older Japanese population and new immigrants from Japan eat traditional foods — such as fish, miso soup and produce — while the younger, racially mixed generation is more fueled by fast food,” Meng said.

About 20 percent of California’s Japanese population identifies as multiracial, according to CHIS data from 2007 to 2012. Among Japanese Americans ages 18 to 34, about 57 percent identify as multiracial, and only 14 percent identify as Japanese only.

Tailored community outreach needed

To address health issues such as binge drinking and hypertension among California’s Japanese-Americans, the authors suggest culturally appropriate interventions tailored to subgroups, community-based prevention programs in non–health care settings, and more study of Japanese health and health behaviors.

“The approaching wave of aging baby boomers will place more demands on families and communities and significantly affect public health, social services and health care systems across the country,” said Dianne Kujubu Belli, chief administrative officer of Keiro Senior HealthCare. “Not only does this report guide Keiro and other Japanese-serving organizations to establish priorities in programming, but researchers and policymakers can study Japanese-Americans’ better health and take steps to promote healthy lifestyles and dietary habits for all future seniors.”

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Statin use in elderly would prevent disease but could carry side effects

Researchers find a tenuous balance between potential benefits and risks.

By Elizabeth Fernandez, UC San Francisco

A new study by UC San Francisco has found that statins can help prevent disease in older adults but must be weighed against potentially serious side effects.

Amid a projected cost of almost $900 billion for cardiovascular disease over the next decade in the U.S., statins are used by nearly half the elderly population in the nation. But in spite of the widespread use, there has been little systematic scrutiny of the potential risks of the drugs in older adults and whether those side effects could offset cardiovascular and other health benefits.

For the statin study, the researchers used a computer simulation model that explored whether statins should be routinely administered to adults 75 or older to prevent heart disease.

They found a tenuous balance: on the one hand, the results showed “tremendous” potential health benefits to be gained including far fewer heart attacks. On the other hand, potential side effects that may have particular consequences in the elderly – including muscle pain and weakness or mild declines in cognitive function – could offset those gains.

The study appears April 21 in Annals of Internal Medicine.

“There’s been a lot of uncertainty over the use of statins in older adults,” said senior author Kirsten Bibbins-Domingo, Ph.D., M.D., a professor of medicine, epidemiology and biostatistics at UCSF. She is also director of the UCSF Center for Vulnerable Populations at San Francisco General Hospital and Trauma Center.

“Prior studies have favored statin use because of the clear benefits to the heart and because serious side effects are rare,” said Bibbins-Domingo. “Unfortunately, we don’t have enough studies in older adults, and as a result don’t know enough about how common or how severe the side effects are. Our study showed that in older adults, even small increases in functional limitations and mild cognitive impairments from statin use could result in net harm.”

An estimated 19 million adults 75 to 94 years old were living in the U.S., according to 2014 statistics, and of those 30 percent were diagnosed with cardiovascular disease, reported the study. Under current rates, older adults are projected to account for 2.5 million myocardial infarctions and 3.1 million deaths related to coronary heart disease over the next decade.

Statins are widely used to combat cardiovascular disease. Before patients embark on using them, typically they discuss the potential benefits and risks with their physicians. To help guide those decisions, researchers in the statin study sought to provide more precise and reliable data on the balance between benefits and harms.

They focused on two side effects that are particularly important to geriatric populations: functional limitations due to muscle pain and weakness and mild cognitive impairment. “Both of these conditions are prevalent in older adults and can have substantial impact on quality of life and ability to live independently,” the authors wrote.

The study was based on a simulation of all U.S. adults 75 to 94 years old, from 2014 through 2023. The researchers simulated the estimated impact of statin use for primary prevention, modeling the use of statins in all older adults without known heart disease.

In their findings, the authors estimated that if all adults in the U.S. 75 to 93 years old without cardiovascular disease were to take statins over the next decade, 105,000 heart attacks and 68,000 deaths would be prevented. Because statins are available as generics and relatively inexpensive, treating all older adults without heart disease would be cost effective, the author reported.

However, the cardiovascular benefits and cost effectiveness would be offset with even a modest increased risk – by 10 to 30 percent – of cognitive impairments or functional limitations, caution the researchers.

They call for additional research to quantify both the potential benefits and harms of statin use in older adults.

The study was funded by the American Heart Association Western States Affiliate (11CRP7210088) and the National Institute on Aging (K01AG039387).

Co-authors from UCSF are Mark J. Pletcher, M.D., M.P.H., associate professor in residence; Pamela G. Coxson, Ph.D., senior statistician David Guzman, M.S., and postdoctoral fellow David Heller, M.D., M.P.H., of the UCSF Department of Medicine. The first author is Michelle Odden, Ph.D., an assistant professor of epidemiology at Oregon State University. Other co-authors are Divya Thekkethala, B.S., of Oregon State University, and Lee Goldman, M.D., M.P.H., of Columbia University in York.

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Healthy elders may hold key to fighting cancer

‘Wellderly’ may have unknowingly fought, beaten cancer; immune systems may hint at how.

The immune systems of healthy elders — the 'wellderly' — may be a protective factor against cancer. (Credit: iStock)

By Kate Rix, UC Newsroom

Could the immune systems of healthy seniors hold clues for beating the most aggressive form of breast cancer?

New evidence from the Scripps Research Institute suggests that some seniors may have successfully fought cancer without ever knowing it, developing antibodies that may hold promising avenues for new therapies.

Scripps researchers have begun mining the DNA in blood samples from the so-called “wellderly” — healthy adults age 80-plus — for the secrets to their long lives.

In the process, they’ve homed in on antibodies that bond with a type of cancer cell for which there is no targeted therapy.

“I thought that the human immune system is really our best defense against cancer,” says Brunie Felding, an investigator at Scripps. “The wellderly have had a healthy long life. My question was: Do these people have antibodies we should look into?”

Battles fought and won

With blood samples that included the combined white blood cells of cancer-free seniors, Felding found what may amount to the footprints, or memories, of past victories against cancer.

Exposed to an “immune library” generated from the wellderly blood samples, a particular protein in aggressive “triple negative” breast cancer cells was recognized by an antibody from the wellderly and sparked particular interest.

The cancer cell protein is part of a signaling pathway. “This could be a driving pathway in this aggressive cancer, an indicator of where to look for therapeutic targets,” says Felding.

The project was funded with two grants from the California Breast Cancer Research Program, which is managed by the UC Office of the President and supported in part by taxpayer donations on the state tax return.

The broader wellderly study, from which Felding obtained the blood sample, is ongoing at Scripps Research and led by professor Eric Topol.

Lingering antibody memory

Felding’s idea was novel: Healthy older women may have successfully fought breast cancer at some point and never known it. When the human body encounters a pathogen, it makes antibodies to neutralize it. Even when the pathogen is gone, the specially adapted antibodies remain in the immune memory, in case the pathogen reappears. A similar principle could control cancer development.

“If there were aberrant cells at some point in a person’s body, but a noticeable cancer never developed, the immune system likely coped with those stray cells, and the antibody memory would still be there years later,” Felding says.

In this study, researchers were specifically looking for how the body copes with what is called triple negative breast cancer. While many breast cancer tumors can be treated with anti-estrogen therapies, there is no targeted treatment for triple negative tumors.

“Finding an effective therapy for these types of breast cancers is one of our main goals in cancer research,” says Felding.

The cancer cells she exposed to the wellderly immune library were from a very aggressive triple negative breast cancer of a woman named Elizabeth, one of Felding’s friends, who died from the disease.

Looking at the genome of Elizabeth’s cancer, Felding and her group saw that the protein Apolipoprotein E, or ApoE, was more than 100-fold enriched during the progression of Elizabeth’s breast cancer.

They also found that this protein was recognized by some of the wellderly antibodies. This could mean two things: The antibodies that recognize ApoE may have certain disease-blocking properties and could hold promise for a targeted therapy. Or, ApoE might be a flashing signpost pointing researchers down a pathway to be analyzed as a possible disease driver.

“Overall, the concept of exploring the immune system is very promising,” Felding said. “The fact that the wellderly blood donors are in their 80s means that their immune memories are very rich.”

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Women, regardless of backgrounds, seek help for ‘got to go’ feeling

Study shows importance of providers discussing urinary incontinence with patients.

By Phyllis Brown, UC Davis

Regardless of their racial, ethnic, educational or socioeconomic background, women seek help for a frustrating — and ubiquitous — feature of becoming “a woman of a certain age:” the need be close to the women’s room.

Those are the findings of a large study by UC Davis of urinary incontinence in menopausal women, based on data from the Study of Women’s Health Across the Nation (SWAN), a nine-year investigation of diverse menopausal women from six sites across the United States. The study is published online today (April 7) in Obstetrics and Gynecology.

The study, of more than 3,302 study participants from such diverse locations as Oakland, Pittsburgh and Detroit, found that most women, regardless of their backgrounds, talked with their health care provider about urinary urgency incontinence — leaking with the immediate need to reach the restroom — or stress incontinence — leaking with “coughing, laughing or sneezing” — over the nine years they were followed.

All of the participants were transitioning through menopause. Some 68 percent of women reported monthly or more frequent urinary incontinence, either leakage with urgency or with coughing, sneezing or exercising.

Earlier studies have suggested that African-American women and women of lower socioeconomic backgrounds were less likely to seek treatment.

“Our study results do not support previous findings that black women or women with lower socioeconomic circumstances are either less likely to seek care only at a higher level of bother of urinary incontinence frequency than white women or women of higher socioeconomic resources,” said Elaine Waetjen, UC Davis professor in the Department of Obstetrics and Gynecology and lead study author.

Rather, Waetjen said, the strongest associations with seeking care were worsening and persistence of symptoms. That is important, Waetjen said, because urinary incontinence is readily treatable.

“By discussing their urinary incontinence with a health care provider, women can learn about the variety of treatment options available to them, from behavioral changes to medications and surgery,” she said.

Other study authors include Guibo Xing, Joy Melnikow and Ellen Gold, all of UC Davis and Wesley O. Johnson of UC Irvine.

The study was funded by the National Institutes of Health, including the Institute of Diabetes and Digestive and Kidney Disease, Office of Research on Women’s Health, Institute on Aging, and Institute of Nursing Research, including grants number DK092864, U01NR004061, U01AG012505, U012535, U01AG02531, U01AG02531, U01AG012539, U01AG012546, U01AG012553, U01AG012554, U01AG012495.

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Even at molecular level, taking it slow helps us cope with stress

UC Berkeley scientists ID new molecular pathway critical to aging.

Illustration of a mitochondrion, a cell’s energy station. Within mitochondria are a multitude of proteins, which must be folded properly to function. UC Berkeley research has linked stress from mitochondrial misfolded proteins to blood stem cell aging, and they found a way to help the cells cope with the damage.

By Sarah Yang, UC Berkeley

UC Berkeley scientists have identified a new molecular pathway critical to aging, and confirmed that the process can be manipulated to help make old blood like new again.

The researchers found that blood stem cells’ ability to repair damage caused by inappropriate protein folding in the mitochondria, a cell’s energy station, is critical to their survival and regenerative capacity.

The discovery, to be published in the March 20 issue of the journal Science, has implications for research on reversing the signs of aging, a process thought to be caused by increased cellular stress and damage.

“Ultimately, a cell dies when it can’t deal well with stress,” said study senior author Danica Chen, an assistant professor in the Department of Nutritional Sciences and Toxicology. “We found that by slowing down the activity of mitochondria in the blood stem cells of mice, we were able to enhance their capacity to handle stress and rejuvenate old blood. This confirms the significance of this pathway in the aging process.”

Mitochondria host a multitude of proteins that need to be folded properly to function correctly. When the folding goes awry, the mitochondrial unfolded-protein response, or UPRmt, kicks in to boost the production of specific proteins to fix or remove the misfolded protein.

Chen’s lab stumbled upon the importance of UPRmt in blood stem cell aging while studying a class of proteins known as sirtuins, which are increasingly recognized as stress-resistance regulators.

The researchers noticed that levels of one particular sirtuin, SIRT7, increase as a way to help cells cope with stress from misfolded proteins in the mitochondria. Notably, SIRT7 levels decline with age.

There has been little research on the UPRmt pathway, but studies in roundworms suggest that its activity increases when there is a burst of mitochondrial growth.

Chen noted that adult stem cells are normally in a quiescent, standby mode with little mitochondrial activity. They are activated only when needed to replenish tissue, at which time mitochondrial activity increases and stem cells proliferate and differentiate. When protein-folding problems occur, however, this fast growth could lead to more harm.

“We isolated blood stem cells from aged mice and found that when we increased the levels of SIRT7, we were able to reduce mitochondrial protein-folding stress,” said Chen. “We then transplanted the blood stem cells back into mice, and SIRT7 improved the blood stem cells’ regenerative capacity.”

The new study found that blood stem cells deficient in SIRT7 proliferate more. This faster growth is due to increased protein production and increased activity of the mitochondria, and slowing things down appears to be a critical step in giving cells time to recover from stress, the researchers found. Chen likened this to an auto accident or stalled car jamming traffic on a freeway.

“You can deal with this congestion by removing all the cars that are blocked, but you can also stop more cars from getting onto the freeway,” she said. “When there’s a mitochondrial protein-folding problem, there is a traffic jam in the mitochondria. If you prevent more proteins from being created and added to the mitochondria, you are helping to reduce the jam.”

Until this study, it was unclear which stress signals regulate the transition of stem cells to and from the quiescent mode, and how that related to tissue regeneration during aging.

“Identifying the role of this mitochondrial pathway in blood stem cells gives us a new target for controlling the aging process,” said Chen.

UC Berkeley co-lead authors of the study are postdoctoral researcher Mary Mohrin and graduate students Jiyung Shin, Yufei Liu and Katharine Brown.

The National Institutes of Health, Ellison Medical Foundation, Glenn Foundation, National Science Foundation and Siebel Stem Cell Institute helped support this research.

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Discovery opens the door to a potential ‘molecular fountain of youth’

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Commentary: Study affirms varied factors contribute to cognitive decline

Editorial: ‘A call for new thoughts about what might influence brain aging.’

Charles DeCarli, UC Davis

By Phyllis Brown, UC Davis

A study published online today (March 16) in JAMA Neurology that finds associations between reduced hippocampal volume (HVa) and being male, but not the gene APOE ɛ4, suggests that there are multiple factors contributing to cognitive decline throughout adulthood, according to an accompanying commentary by UC Davis Alzheimer’s Disease Center Director Charles DeCarli.

The research, by Clifford R. Jack and colleagues at the Mayo Clinic and Foundation, compared age, sex and apolipoprotein E ɛ4 (APOE ɛ4) genotype effects on memory, brain structure and the amyloid brain plaques associated with Alzheimer’s disease, using positron emission tomography (PET) in 1,246 cognitively normal individuals between the ages of 30 and 95.

The study found:

  • Overall memory worsened from age 30 through the 90s.
  • HVa worsened gradually from age 30 to the mid-60s and more steeply after that with advancing age.
  • Median amyloid accumulation seen on PET scans was low until age 70 but increased after that.
  • Memory was worse in men than women overall, especially after 40.
  • The HVa was lower in men than women overall, especially after 60.
  • For both males and females, memory performance and HVa were not different by APOE ɛ4 carrier status at any age.

“If one ascribes religiously to the concept that a large proportion of cognitive differences with age are driven by incipient disease, then one might expect that memory performance — a cognitive ability that changes most dramatically with age and is common to Alzheimer’s disease — would follow increasing levels of associated cerebral amyloid and be strongly associated with hippocampal atrophy. In their article Jack et al present new information that challenges the notion that amyloid accumulation explains memory performance across the entire age range,” DeCarli says in his editorial.

“Importantly, this work does not only address the likely highly significant impact of cerebral amyloid accumulation on dementia risk, but also extends current knowledge relating to the impact of the aging process across the spectrum of ages 30 to 95 years to brain structure, amyloid accumulation and memory performance among cognitively normal individuals.”

DeCarli notes that “If one tenaciously holds to the notion that the insidious consequences of other diseases may be contributing to these earlier differences, vascular brain injury is an obvious candidate. Vascular risk factors, such as diabetes mellitus, are associated with subtle cognitive impairment among individuals aged 47 to 57 years and hypertension is associated with significantly greater cerebral atrophy among individuals 40 years on average.”

Other contributing factors include genetic influences, which include sex differences and the “major effects” of APOE ɛ4 genotype on amyloid retention beyond age 70 years.

“Understanding the basic biology of these early processes is likely to substantially inform us about ways in which we can maintain cognitive health and optimize resistance to late-life dementia. However, such work requires the necessary motivation found by seminal work, such as that of Jack et al, which tell us where and when to investigate these processes. Establishing what is normal creates avenues for new research, increasing the likelihood of discovering novel therapeutics for late-life disease states, which is a laudable goal indeed,” DeCarli says.

For more information, visit alzheimer.ucdavis.edu.

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Keeping older drivers safe

National grant funds project to address safety and well-being of older drivers.

By Jackie Carr, UC San Diego

Researchers at the UC San Diego School of Medicine will share a $12 million grant with peer institutions across the United States to better understand the factors that influence the safety of older drivers, such as physical and cognitive functions, medical conditions, medications and adoption of vehicle technologies.

The study, called the Longitudinal Research on Aging Drivers (LongROAD) project is funded by the AAA Foundation for Traffic Safety and led by Guohua Li, Dr.P.H., M.D., professor of epidemiology at Columbia University Mailman School of Public Health. As the largest research initiative of the AAA Foundation, the LongROAD project represents a long-term commitment by the agency to support the well-being of older drivers.

“To many older adults, driving is essential for maintaining mobility and independence,” said Linda Hill, M.D., M.P.H., LongROAD co-investigator, professor and specialist in preventive medicine in the UC San Diego School of Medicine. “Unfortunately, declines in physical and cognitive functions may compromise the safety of these drivers. This project will provide insight into how to help older adults retain their driving privilege as long as safely possible, and how to provide them with comfortable and convenient transportation alternatives when they stop driving.”

A total of 3,000 active drivers aged 65-79 years will be recruited from five study sites in California, Colorado, Maryland, Michigan and New York, and follow these drivers through annual assessments and interviews. To learn about their driving patterns, researchers will fit each driver’s vehicle with a GPS device.

“By 2029, more than one in five Americans will be over the age of 65. Understanding their driving patterns, health, and transportation needs is a matter of public health and safety for all drivers,” said Hill. “Yet we have very limited observed data about the dynamic interplay between health and driving safety during the process of aging – a knowledge gap identified by the National Institute on Aging as a key strategic research priority. This project aims to close that gap.”

The LongROAD project will enhance the extensive outreach that Hill has achieved as director of the Training, Research and Education for Driving Safety (TREDS) project at UC San Diego. TREDS training for health care professionals and law enforcement increases awareness and management of impairments common with aging that can impact driving ability. More than 6,000 health professionals and 3,500 law enforcement officers in California have received TREDS training, and several thousand more have been reached nationwide.

Participating institutions in the LongROAD project include Columbia University, University of Michigan, the Urban Institute, Bassett Research Institute, Johns Hopkins University, and University of Colorado, Denver.

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Brain region vulnerable to aging is larger in those with longevity gene variant

1 in 5 carry KLOTHO allele associated with better cognition.

The dorsolateral prefrontal cortex, depicted in blue and red, is larger and linked with better function in those who carry one copy of the KLOTHO gene variant. (Illustration by Michael Griffin Kelly)

By Laura Kurtzman, UC San Francisco

People who carry a variant of a gene that is associated with longevity also have larger volumes in a front part of the brain involved in planning and decision-making, according to researchers at UC San Francisco.

The finding bolsters their previous discovery that middle-aged and older people who carry a single copy of the KLOTHO allele, called KL-VS, performed better on a wide range of cognitive tests. When they modeled KL-VS in mice, they found this strengthened the connections between neurons and enhanced learning and memory.

KLOTHO codes for a protein, called klotho, which is produced in the kidney and brain and regulates many different processes in the body. About 1 in 5 people carry a single copy of KL-VS, which increases klotho levels and is associated with a longer lifespan and better heart and kidney function. A small minority, about 3 percent, carries two copies, which is associated with a shorter lifespan.

Examining part of prefrontal cortex

In the current study, published today (Jan. 27), in Annals of Clinical and Translational Neurology, researchers scanned the brains of 422 cognitively normal men and women aged 53 and older to see if the size of any brain area correlated with carrying one, two or no copies of the allele.

They found that the KLOTHO gene variant predicted the size of a region called the right dorsolateral prefrontal cortex (rDLPFC), which is especially vulnerable to atrophy as people age. Deterioration in this area may be one reason why older people have difficulty suppressing distracting information and doing more than one thing at a time.

Researchers found that the rDLPFC shrank with age in all three groups, but those with one copy of KL-VS – about a quarter of the study group – had larger volumes than either non-carriers or those with two copies. Researchers also found that the size of the rDLPFC predicted how well the three groups performed on cognitive tests, such as working memory – the ability to keep a small amount of newly acquired information in mind – and processing speed. Both tests are considered to be good measures of the planning and decision-making functions that the rDLPFC controls.

“We’ve known for a long time that people lose cognitive abilities as they age, but now we’re beginning to understand that factors like klotho can give people a boost and confer resilience in aging,” said senior author Dena Dubal, M.D., Ph.D., assistant professor of neurology at UCSF and the David A. Coulter Endowed Chair in Aging and Neurodegenerative Disease. “Genetic variation in KLOTHO could help us predict brain health and find ways to protect people from the devastating diseases that happen to us as we grow old, like Alzheimer’s and other dementias.”

Bigger size means better function

In statistical tests, the researchers concluded that the larger rDLPFC volumes seen in single copy KL-VS carriers accounted for just 12 percent of the overall effect that the variant had on the abilities tested.

However, the allele may have other effects on the brain, such as increasing levels or changing the actions of the klotho protein to enhance synaptic plasticity, or the connections between neurons. In a previous experiment, they found that raising klotho in mice increased the action of a cell receptor critical to forming memories.

“The brain region enhanced by genetic variation in KLOTHO is vulnerable in aging and several psychiatric and neurologic diseases including schizophrenia, depression, substance abuse and frontotemporal dementia,” said Jennifer Yokoyama, Ph.D., first author and assistant professor of neurology at UCSF. “In this case, bigger size means better function. It will be important to determine whether the structural boost associated with carrying one copy of KL-VS can offset the cognitive deficits caused by disease.”

Other authors of the study include Virginia Sturm, Luke Bonham, Joel Kramer and Bruce Miller of UCSF; Eric Klein and Giovanni Coppola of UCLA; Lei Yu and David Bennett of Rush University Medical Center; and Konstantinos Arfanakis of Rush and the Illinois Institute of Technology.

The study was funded by the Larry L. Hillblom Foundation, the National Institute on Aging, the American Federation for Aging Research, the Coulter-Weeks Foundation and the Bakar Foundation.

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The ‘oddball organism’ that helped win a Nobel Prize

Tetrahymena became a model for research into aging.

By Arezu Sarvestani, UC San Francisco

What lives in freshwater ponds, comes in seven different sexes and helped UC San Francisco’s Elizabeth Blackburn win a Nobel Prize? The answer is the humble Tetrahymena, the single-celled organism that became a model for research into aging.

Many modern advances in health and medicine wouldn’t be possible without the tiny creatures that help researchers study life. That’s why Blackburn, Ph.D., gave a shout out to Tetrahymena when she accepted the Nobel Prize for Physiology or Medicine in 2009. Blackburn was honored for her work discovering telomeres and the telomerase enzyme, now known to play important roles in how and why cells degrade as we age.

Tetrahymena have a large number of short, paired chromosomes that made them ideal candidates for DNA sequencing in Blackburn’s early work. While studying the pear-shaped protozoa in the 1980s, Blackburn found that they were able to shrink and regrow their DNA, a concept that flew in the face of biological tenets of the time. Exploration of that phenomenon led Blackburn and colleagues Jack Szostak and Carol Greider to discover telomeres, the protective string of code at the ends of chromosomes, and telomerase, which protects chromosomes from degrading over time – in humans as well as Tetrahymena.

“If we had not been able to use these seemingly oddball organisms because of the advantages they offered as experimental systems for biological research, I don’t know when we would have learned about telomeres and telomerase,” Blackburn said during her Nobel Prize acceptance speech.

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Many seniors who fall repeatedly don’t seek medical attention

Study finds health care workers also often fail to counsel seniors on preventing future falls.

More than half a million older Californians — 12.6 percent of the state’s senior population — fall more than once a year, but nearly 60 percent of them fail to seek medical attention afterward, according to a new study by the UCLA Center for Health Policy Research.

The study also found that among those who did seek treatment, 40 percent did not receive counseling from a medical provider about how to prevent future falls.

Falls are the leading injury-related cause of death and need for medical care among Californians age 65 and older, according to the study. In 2012, more than 1,800 seniors died after falling and seniors’ fall-related injuries resulted in more than 72,000 hospitalizations.

“There is a cost in terms of both lives and resources when doctors fail to talk to seniors who have already fallen about how to prevent future falls,” said Steven Wallace, associate director of the Center for Health Policy Research and author of the study.

Using data from the 2011–12 California Health Interview Survey, the study found older seniors are twice as likely as younger seniors to have multiple falls: nearly 1 in 5 people 85 and older reported that they fell more than once a year, compared with 1 in 10 of those aged 65 to 74. Nearly a quarter of seniors who have suffered a stroke, and almost 20 percent of those with any disability, had multiple falls. Twenty-six percent of seniors with moderate mental impairment had multiple falls, as did 38 percent with severe mental impairment.

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Keeping roadways safe as America grays

Doctors, law enforcement receive training in assessing elderly drivers.

Every day in America roughly 10,000 people turn age 65. To help keep roadways safe as America grays and to help preserve the freedom of mobility of older drivers, researchers at the UC San Diego School of Medicine are training law enforcement officers to recognize warning signs of impaired driving skills and to take appropriate, compassionate action. They are also training doctors to think more about their patients’ ability to drive safely with age.

The educational program, known as Training, Research and Education for Driving Safety (TREDS) was recently awarded its eighth consecutive year of funding from the California Office of Traffic Safety through the National Highway Traffic Safety Administration.

“Our goal is to reduce the number of fatalities involving older drivers and to prolong the time that seniors can drive safely,” said Linda Hill, M.D., M.P.H., professor of family and preventive medicine and TREDS program director.

“Our program focuses on educating people about the effects of aging on driving skills and the need to assess older people for driving impairments,” she said. “We also teach doctors about conditions and medications that can impact a persons ability to drive safely at any age, especially older adults.”

This year’s funding provides continued support for training courses for physicians and local law enforcement officers in Southern California. In addition, the UC San Diego team will offer a train-the-trainer program to law enforcement officers who go on to teach the program material to colleagues. A primary focus is identifying signs of dementia and other medical conditions that can impair safe driving. Identified drivers may be referred to the California Department of Motor Vehicles for further assessment.

In the coming year, researchers say they will continue to expand their training program to reach law enforcement officers throughout the state.

Since 2006, UC San Diego researchers have conducted in-person TREDS training to more than 9,000 doctors and 3,000 law enforcement officers. Companion TV, radio and online efforts have reached an estimate 1 million people.

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