Genes and Vascular Risk Modify Effects of Aging On Brain and Cognition

Efforts to understand how the aging process affects the brain and cognition have expanded beyond simply comparing younger and older adults.

"Everybody ages differently. By looking at genetic variations and individual differences in markers of vascular health, we begin to understand that preventable factors may affect our chances for successful aging," said Wayne State University psychology doctoral student Andrew Bender, lead author of a study supported by the National Institute on Aging of the National Institutes of Health and now in press in the journal Neuropsychologia.

The report, "Age-related Differences in Memory and Executive Functions in Healthy APOE ε4 Carriers: The Contribution of Individual Differences in Prefrontal Volumes and Systolic Blood Pressure," focuses on carriers of the ε4 variant of the apolipoprotein (APOE) gene, present in roughly 25 percent of the population. Compared to those who possess other forms of the APOE gene, carriers of the ε4 allele are at significantly greater risk for Alzheimer's, dementia and cardiovascular disease.

Many studies also have shown that nondemented carriers of the APOE ε4 variant have smaller brain volumes and perform less well on cognitive tests than carriers of other gene variants. Those findings, however, are not consistent, and a possible explanation may come from examining interactions between the risky genes and other factors, such as markers of cardiovascular health. Prior research in typical samples of older adults has shown that indeed other vascular risk factors -- such as elevated cholesterol, hypertension or diabetes -- can exacerbate the impact of the APOE ε4 variant on brain and cognition, but it is unclear if such synergy of risks is present in healthy adults.

Thus, Wayne State researchers evaluated a group of volunteers from 19 to 77 years of age who self-reported as exceptionally healthy on a questionnaire that screened for a number of conditions, representing a "best case scenario" of healthy aging. The research project, led by Naftali Raz, Ph.D., professor of psychology and director of the Lifespan Cognitive Neuroscience Research Program at WSU's Institute of Gerontology, tested different cognitive abilities known for their sensitivity to aging and the effects of the APOE ε4 variant. Those abilities include speed of information processing, working memory (holding and manipulating information in one's mind) and episodic memory (memory for events).

Researchers also measured participants' blood pressure, performed genetic testing to determine which APOE variant participants carried, and measured the volumes of several critical brain regions using a high-resolution structural magnetic resonance imaging brain scan. Bender and Raz showed that for older APOE ε4 carriers, even minor increases in systolic blood pressure (the higher of the two numbers that are reported in blood pressure measures) were linked with smaller volumes of the prefrontal cortex and prefrontal white matter, slower speed of information processing, reduced working memory capacity and worse verbal memory. Notably, they said, that pattern was not evident in those who lacked the ε4 gene variant.

The study concludes that the APOE ε4 gene may make its carriers sensitive to negative effects of relatively subtle elevations in systolic blood pressure, and that the interplay between two risk factors, genetic and physiological, is detrimental to the key brain structures and associated cognitive functions.

"Although genes play a significant role in shaping the effects of age and vascular risk on the brain and cognition, the impact of single genetic variants is relatively small, and there are quite a few of them. Thus, one's aging should not be seen through the lens of one's genetic profile," cautioned the study's authors. They continued, "The negative impact of many genetic variations needs help from other risk factors, and while there isn't much one can do about genes, a lot can be done about vascular risk factors such as blood pressure or cholesterol."

"Everybody should try to keep those in check, although people with certain genetic variants more so than others." Raz said. "Practically speaking, even with the best deck of genetic cards dealt to you, it still makes sense to reduce risk through whatever works: exercise, diet or, if those fail, medication."

Because the study is part of a longitudinal project, he and Bender said the immediate future task now is to determine how the interaction between risky genes and vascular risk factors affect the trajectory of age-related changes -- not differences, as in this cross-sectional study -- in brain and cognition.

Source: Wayne State University - Office of the Vice President for Research [May 09, 2012]

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Keep aging brains sharp

Exercising, eating a healthy diet and playing brain games may help you keep your wits about you well into your 80s and even 90s, advises a new book by researchers at George Mason University. 

"These are all cheap, easy things to do," says Pamela Greenwood, an associate professor in the Department of Psychology on Mason's Fairfax, Va. campus. "We should all be doing them anyway. You should do them for your heart and health, so why not do them for your brain as well?" 

For the past 20 years, Greenwood and Raja Parasuraman, University Professor of Psychology, have studied how the mind and brain age, focusing on Alzheimer's disease. Their book, "Nurturing the Older Brain and Mind" published by MIT Press, came out in March. The cognitive neuroscientists geared the book to middle-aged readers who want to keep their mental snap. 

"We know that if we can put off dementing illnesses even by a year or two through lifestyle changes, that will reduce the number of people with Alzheimer's disease, which is reaching epidemic proportions," Parasuraman says. 

Not everyone's brain declines when retirement age hits. "You can look at a group of 65-year-olds — some are in nursing homes, and some are running the world," Greenwood says. 

Now that more workers are staying on the job longer for economic reasons and because countries are upping the retirement age, keeping the mind agile becomes paramount, Parasuraman says. 

For the book, Parasuraman and Greenwood examined only scientific studies, theirs and others, ranging from neurological to physiological. A few surprises leaped out of the data. 

"Several old dogmas were overturned," Parasuraman says. "There's the tired old joke that we're losing brain cells as we age — maybe starting as young as 20 or 30 — and it's all downhill after that." 

Not so, new research reveals. Not only are some 60-year-olds as sharp as 20-year-olds, but their brains still create new cells. Brain cells may not grow as fast as bone or skin cells, but grow they do, particularly in the hippocampus. "It's the area of the brain that's very important to memory and is affected by Alzheimer's disease," Parasuraman says. 

Novel experiences and new learning help new brain cells become part of the circuitry. Parasuraman points to a study of terminally ill cancer patients whose brains were still forming new neurons. "If a person who's in a terminally ill state can generate new neurons, then surely healthy people can," Parasuraman says. 

Brain games and new experiences may build up "white matter," which insulates neurons as they carry signals, Greenwood says. In older brains, this white matter insulation develops holes and signals go awry. 

Older adult gamers are winning skills to help them move through life, Parasuraman says. "We are looking at everyday problem solving," he says. "Are you better at balancing a checkbook? Are you better at making decisions in a grocery store? We're finding you get better at those tasks (after playing the video games in the study)." 

Moving large muscle groups also builds brain matter. In one study detailed in the book, older, sedentary people began walking or did stretching exercises for 45 minutes, three times a week. "Those people actually became smarter over time," Greenwood says. "You don't have to be running Ironman marathons. You can just walk briskly three or four times a week." 

Another best bet for an active mind is a nutritious diet that limits calories to the minimum amount needed to keep a body healthy. No starvation diets, though. "The strongest evidence we have is not very pleasant, which is dietary restriction, reducing calories," Parasuraman says. "That clearly improves longevity and cognition. The evidence in animals is very strong. Such dietary restriction may never be popular. But perhaps every-other-day fasting as an approximation to it is something people would tolerate: You eat normally one day, and the next day you don't." 

Popping supplements won't fill a nutritionally deficient diet, Parasuraman says. "A lot of people think, 'I can eat junk food and then take a pill.' No. You have to eat fruits and vegetables, leafy vegetables. It has to be part of the regular diet because otherwise it's not absorbed." 

Fat cells help make up cell membranes. The unsaturated fats found in fish and olive oils may boost flexibility in these membranes. The more flexible membranes are, the better they may work, scientists theorize. Saturated fats such as butter have to go because these fats vie with healthy fats for a place in the cell membrane, Greenwood explains. 

Greenwood and Parasuraman want people to know that getting old doesn't mean getting senile. "The bottom line message of the book is really a hopeful one," Greenwood says. "There are lots of things that you can do (to keep your brain healthy)." 

Source: George Mason University [April 04, 2012]

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Healthy aging begins in the womb

Ageing is a complex process involving physical, psychological, and environmental factors. Scientists believe that ageing can be programmed in the womb. One example of stress during pregnancy is the administration of glucocorticoids, i. e. synthetic stress hormones to accelerate fetal lung maturation in premature labor to allow breathing after birth. Could exposure to these stress hormones have an effect on health later in life? 

"We know from previous studies that children whose mothers received glucocorticoids during pregnancy are less stress tolerant and have more concentration problems than their peers," reported Professor Matthias Schwab, the Neurologist heading the project. "Stress signal regulation is permanently disturbed and appears to lead to early ageing, in particular, of the brain", he added. 

The scientists examine several risk groups. One consists of 10-year-olds born at the University Hospital Jena whose mothers had treatment with glucocorticoids during pregnancy. Two other groups are being followed up by psychologists at the University of Leuven in Belgium and include two-year-olds and 25-year-olds whose mothers suffered from stress during pregnancy. 

"A unique group studied at the Academic Medical Centre, University of Amsterdam includes persons born in Holland during the Dutch „Hunger Winter", of 1944/45," reported Prof. Schwab. 

Scientists involved in the project use state-of-the art neuropsychological, neurophysiological, and MRI methods to analyse and compare biological and real age of the brain. The biotechnology companies Life Length in Madrid and Biocrates in Innsbruck measure biological age in chromosomes and screen blood samples to determine metabolic blood markers of age. 

"Environmental factors such as exposure to stress hormones or malnutrition during pregnancy change the readout of genetic information permanently," reported Matthias Platzer, Head of Genome Analysis at the Leibniz Institute for Age Research in Jena. 

"These epigenetic processes significantly change stress sensitivity for the rest of life," explained Prof Schwab. „Increased stress sensitivity makes one vulnerable to age-related diseases such as stroke and depression," he added. 

In experimental studies, researchers aim to determine the period during pregnancy in which the brain is particularly vulnerable to stress. An important aspect of the research also involves studying a group of primates kept in Texas for possible translation of the findings to human subjects. 

Understanding the biology of healthy ageing is desperately needed due to the worldwide ageing population and the economic costs of treating age-related diseases. 

"Environmental influences during life in the womb are early determinants for life-long good health and may be a target for preventive measures against early-ageing and age-related diseases," explained Prof. Schwab.  

Source: Friedrich-Schiller-Universitaet Jena [March 08, 2012]

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Why the brain is more reluctant to function as we age

New findings, led by neuroscientists at the University of Bristol and published this week in the journal Neurobiology of Aging, reveal a novel mechanism through which the brain may become more reluctant to function as we grow older. 

It is not fully understood why the brain's cognitive functions such as memory and speech decline as we age. Although work published this year suggests cognitive decline can be detectable before 50 years of age. The research, led by Professor Andy Randall and Dr Jon Brown from the University's School of Physiology and Pharmacology, identified a novel cellular mechanism underpinning changes to the activity of neurones which may underlie cognitive decline during normal healthy aging. 

The brain largely uses electrical signals to encode and convey information. Modifications to this electrical activity are likely to underpin age-dependent changes to cognitive abilities. 

The researchers examined the brain's electrical activity by making recordings of electrical signals in single cells of the hippocampus, a structure with a crucial role in cognitive function. In this way they characterised what is known as "neuronal excitability" — this is a descriptor of how easy it is to produce brief, but very large, electrical signals called action potentials; these occur in practically all nerve cells and are absolutely essential for communication within all the circuits of the nervous system. 

Action potentials are triggered near the neurone's cell body and once produced travel rapidly through the massively branching structure of the nerve cell, along the way activating the synapses the nerve cell makes with the numerous other nerve cells to which it is connected. 

The Bristol group identified that in the aged brain it is more difficult to make hippocampal neurones generate action potentials. Furthermore they demonstrated that this relative reluctance to produce action potential arises from changes to the activation properties of membrane proteins called sodium channels, which mediate the rapid upstroke of the action potential by allowing a flow of sodium ions into neurones. 

Professor Randall, Professor in Applied Neurophysiology said: "Much of our work is about understanding dysfunctional electrical signalling in the diseased brain, in particular Alzheimer's disease. We began to question, however, why even the healthy brain can slow down once you reach my age. Previous investigations elsewhere have described age-related changes in processes that are triggered by action potentials, but our findings are significant because they show that generating the action potential in the first place is harder work in aged brain cells. 

"Also by identifying sodium channels as the likely culprit for this reluctance to produce action potentials, our work even points to ways in which we might be able modify age-related changes to neuronal excitability, and by inference cognitive ability." 

Source: University of Bristol [February 01, 2012]

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Music training has biological impact on aging process

Age-related delays in neural timing are not inevitable and can be avoided or offset with musical training, according to a new study from Northwestern University. The study is the first to provide biological evidence that lifelong musical experience has an impact on the aging process. 

Measuring the automatic brain responses of younger and older musicians and non-musicians to speech sounds, researchers in the Auditory Neuroscience Laboratory discovered that older musicians had a distinct neural timing advantage. 

"The older musicians not only outperformed their older non-musician counterparts, they encoded the sound stimuli as quickly and accurately as the younger non-musicians," said Northwestern neuroscientist Nina Kraus. "This reinforces the idea that how we actively experience sound over the course of our lives has a profound effect on how our nervous system functions." 

Kraus, professor of communication sciences in the School of Communication and professor of neurobiology and physiology in the Weinberg College of Arts and Sciences, is co-author of "Musical experience offsets age-related delays in neural timing" published online in the journal Neurobiology of Aging. 

"These are very interesting and important findings," said Don Caspary, a nationally known researcher on age-related hearing loss at Southern Illinois University School of Medicine. "They support the idea that the brain can be trained to overcome, in part, some age-related hearing loss." 

"The new Northwestern data, with recent animal data from Michael Merzenich and his colleagues at University of California, San Francisco, strongly suggest that intensive training even late in life could improve speech processing in older adults and, as a result, improve their ability to communicate in complex, noisy acoustic environments," Caspary added. 

Previous studies from Kraus' Auditory Neuroscience Laboratory suggest that musical training also offset losses in memory and difficulties hearing speech in noise -- two common complaints of older adults. The lab has been extensively studying the effects of musical experience on brain plasticity across the life span in normal and clinical populations, and in educational settings. 

However, Kraus warns that the current study's findings were not pervasive and do not demonstrate that musician's have a neural timing advantage in every neural response to sound. "Instead, this study showed that musical experience selectively affected the timing of sound elements that are important in distinguishing one consonant from another." 

The automatic neural responses to speech sounds delivered to 87 normal-hearing, native English-speaking adults were measured as they watched a captioned video. "Musician" participants began musical training before age 9 and engaged consistently in musical activities through their lives, while "non-musicians" had three years or less of musical training.  

Source: Northwestern University [January 30, 2012]

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Lifelong brain-stimulating habits linked to lower Alzheimer’s protein levels

A new study led by researchers at the University of California, Berkeley, provides even more reason for people to read a book or do a puzzle, and to make such activities a lifetime habit. 

PET scans reveal amyloid plaques, which appear as warm colors such as red and orange. The middle scan is from a person with no symptoms of cognitive problems, but with evident levels of amyloid plaque in the brain [Credit: Susan Landau and William Jagust]

Brain scans revealed that people with no symptoms of Alzheimer’s who engaged in cognitively stimulating activities throughout their lives had fewer deposits of beta-amyloid, a destructive protein that is the hallmark of the disease. 

While previous research has suggested that engaging in mentally stimulating activities – such as reading, writing and playing games – may help stave off Alzheimer’s later in life, this new study identifies the biological target at play. This discovery could  guide future research into effective prevention strategies. 

“These findings point to a new way of thinking about how cognitive engagement throughout life affects the brain,” said study principal investigator Dr. William Jagust,  a professor with joint appointments at UC Berkeley’s Helen Wills Neuroscience Institute, the School of Public Health and Lawrence Berkeley National Laboratory. “Rather than simply providing resistance to Alzheimer’s, brain-stimulating activities may affect a primary pathological process in the disease. This suggests that cognitive therapies could have significant disease-modifying treatment benefits if applied early enough, before symptoms appear.” 

An estimated 5.4 million Americans live with Alzheimer’s disease, but the numbers are growing as baby boomers age. Between 2000 and 2008, deaths from Alzheimer’s increased 66 percent, making it the sixth-leading killer in the country. There is currently no cure, but a draft of the first-ever National Alzheimer’s Plan, released this week, revealed that the U.S. government is aiming for effective Alzheimer’s treatments by 2025. 

The new study, to be published Monday, Jan. 23, in the Archives of Neurology, puts the spotlight on amyloid – protein fibers folded into tangled plaques that accumulate in the brain. Beta-amyloid is considered the top suspect in the pathology of Alzheimer’s disease, so finding a way to reduce its development has become a major new direction of research. 

A molecular model of amyloid protein fibrils. Formed when mis-folded proteins self-assemble into fibrous sheet structures, they are found in the brains of sufferers of Alzheimer's disease [Credit: Susan Landau and William Jagust]

The researchers note that the buildup of amyloid can also be influenced by genes and aging – one-third of people age 60 and over have some amyloid deposits in their brain – but how much reading and writing one does is under each individual’s control. 

“This is the first time cognitive activity level has been related to amyloid buildup in the brain,” said study lead author Susan Landau, research scientist at the Helen Wills Neuroscience Institute and the Berkeley Lab. “Amyloid probably starts accumulating many years before symptoms appear. So it’s possible that by the time you have symptoms of Alzheimer’s, like memory problems, there is little that can be done to stop disease progression. The time for intervention may be much sooner, which is why we’re trying to identify whether lifestyle factors might be related to the earliest possible changes.” 

The researchers asked 65 healthy, cognitively normal adults aged 60 and over (average age was 76) to rate how frequently they participated in such mentally engaging activities as going to the library, reading books or newspapers, and writing letters or email. The questions focused on various points in life from age 6 to the present. 

The participants took part in extensive neuropsychological testing to assess memory and other cognitive functions, and received positron emission tomography (PET) scans at the Berkeley Lab using a new tracer called Pittsburgh Compound B that was developed to visualize amyloid. The results of the brain scans of healthy older individuals with various levels of lifetime cognitive activity were compared with those of 10 patients diagnosed with Alzheimer’s disease and 11 healthy people in their 20s. 

The researchers found a significant association between higher levels of cognitive activity over a lifetime and lower levels of beta-amyloid in the PET scans. They analyzed the impact of other factors such as memory function, physical activity, self-rated memory ability, level of education and gender, and found that lifelong cognitive engagement was independently linked to amyloid deposition. 

Notably, the researchers did not find a strong connection between amyloid deposition and levels of current cognitive activity alone. 

“What our data suggests is that a whole lifetime of engaging in these activities has a bigger effect than being cognitively active just in older age,” said Landau. 

The researchers are careful to point out that the study does not negate the benefits of kicking up brain activity in later years. 

“There is no downside to cognitive activity. It can only be beneficial, even if for reasons other than reducing amyloid in the brain, including social stimulation and empowerment,” said Jagust. “And actually, cognitive activity late in life may well turn out to be beneficial for reducing amyloid. We just haven’t found that connection yet.” 

Other study authors include researchers from UC San Francisco’s Memory and Aging Center and Department of Neurology, and Rush University Medical Center’s Alzheimer’s Disease Center in Chicago. 

The National Institutes of Health and the Alzheimer’s Association helped support this research. 

Author: Sarah Yang | Source: UC Berkeley [January 23, 2012]

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Genetic study offers clues to how intelligence changes through life

Scientists have estimated for the first time the extent to which genes determine changes in intelligence across the human life course. The study found that genetic factors may account for about 24 per cent of changes in intelligence between childhood and old age. The findings also suggest that many of the genes that affect intelligence in childhood also influence intelligence in old age, according to the study published in Nature. The study, by researchers at the Universities of Edinburgh and Queensland and Aberdeen suggests that the largest influence on changes in intelligence is probably environmental. 

DNA from cool angle [Credit: © Dmitry Sunagatov/Fotolia.com]

Identifying genetic influences on intelligence could help us to understand the relationship between knowledge and problem solving and an individual’s outcomes in life, and especially to understand why some people age better than others in terms of intelligence. The researchers combined DNA analysis with data from people who took intelligence tests aged 11 and again aged 65 to 79. The scientists examined more than half a million genetic markers in about 2,000 people to work out how genetically similar they were, even though they were not related. 

The new findings were made possible because Scotland has a rich source of cognitive test data. In June 1932 and June 1947. Intelligence tests were carried out on almost all children born in Scotland in 1921 and 1936, respectively. For the present study, about 2000 of these people were traced and re-tested in old age. 

Professor Ian Deary of the University of Edinburgh’s Centre for Cognitive Ageing and Cognitive Epidemiology, said: “Until now, we have not had an estimate of how much genetic differences affect how intelligence changes across a lifetime. These new findings were possible because our research teams were able to combine a range of valuable resources.    The results partly explain why some people’s brains age better than others. We are careful to suggest that our estimates do not have conventional statistical significance, but they are nevertheless useful because such estimates have been unavailable to date.”  

Professor Peter Visscher of the University of Queensland, said: “Unique data and new genome technologies combined with novel analysis methods allowed us to tackle questions that were not answerable before. The results also strongly suggest how important the environment is helping us to stay sharp as we age. Neither the specific genetic nor environmental factors were identified in this research. Our results provide the warrant for others and ourselves to search for those.” 

Professor Paul Haggarty from the University of Aberdeen Rowett Institute of Nutrition and Health said: "The extensive historical information collected in the Aberdeen and Lothian cohorts included in this study will also make them particularly useful when trying to track down the precise way in which genes and the environment interact to influence cognition throughout life." 

Professor Emeritus of Mental Health at the University of Aberdeen, Lawrence Whalley said: "The Nature research report is a milestone in a long-term research programme that began in Aberdeen in 1997 and was expanded to Edinburgh in 2000. This research collaboration between the universities of Aberdeen and Edinburgh has yielded over 100 joint scientific papers that have added considerably to our understanding of mental decline in old age, and the beginnings of dementia. 

“In this paper, our already substantial collaboration was strengthened by novel methods of data analysis developed by a team in Australia. Using unique Aberdeen and Edinburgh data, with our Australian colleagues we were able to tease apart the overall effects of genes and the environment on causes and courses of mental decline. These findings will encourage others working with complex diseases of old age to apply the same methods to their findings from long-term ageing research." 

Source: University of Aberdeen [January 19, 2012]

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Permafrost bacteria may slow down aging

A hardy type of bacteria recently discovered in the permafrost of Siberia could help slow down the ageing process, Russian scientists claimed on Tuesday. 

The species of bacteria -- given the name Bacillius F -- was found in laboratory tests to have shown signs of slowing down the process of ageing on mice, the Russian Academy of Sciences (RAN) said. 

The Siberian branch of the RAN said Bacillius F lags 3 million years behind similar bacteria in evolutionary terms, according to the characteristics of proteins and some other factors. 

"Taking into consideration the unusual living environment, one can only marvel at the resilience of these bacteria," it said. 

It added that the organisms found in Russia's northern region of Yakutia -- home to the coldest inhabited area on the planet -- reproduce at just 5 degrees Celsius. 

"We just thought: since the bacteria were found in the permafrost where they were successfully preserved they will possibly have mechanisms of retaining viability," added Nadezhda Mironova, senior research scientist at the Institute of Chemical Biology and Fundamental Medicine of the Russian Academy of Sciences. 

"This is what happened," she was quoted as saying. 

Injections of the bacteria into mice have helped boost the natural defences of the animals as they grew older. 

"Bacillius F injections have favourably affected the quality of being of the aging animals," the Russian scientists said. 

"First and foremost, this concerns immunity and the speed of its activation." 

Experiments have shown that metabolism in the tested mice have increased by 20 to 30 percent, the scientists said, adding that the bacterium may also reduce instances of senile blindness but not the emergence of tumours. 

The Russian Academy of Sciences did not say how many mice were tested, adding more animals were needed for the experiments to be more reliable. The mice from a test group lived longer than those in a control group however, it said, calling the results "impressive." 

Source: AFP [January 17, 2012]

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Why Are Older People Happier?

Older people tend to be happier. But why? Some psychologists believe that cognitive processes are responsible -- in particular, focusing on and remembering positive events and leaving behind negative ones; those processes, they think, help older people regulate their emotions, letting them view life in a sunnier light. "There is a lot of good theory about this age difference in happiness," says psychologist Derek M. Isaacowitz of Northeastern University, "but much of the research does not provide direct evidence" of the links between such phenomena and actual happiness. 

In a new article in Perspectives on Psychological Science, a journal published by the Association for Psychological Science, Isaacowitz and the late Fredda Blanchard-Fields of Georgia Institute of Technology argue for more rigorous research. 

Researchers, including the authors, have found that older people shown pictures of faces or situations tend to focus on and remember the happier ones more and the negative ones less. Other studies have discovered that as people age, they seek out situations that will lift their moods -- for instance, pruning social circles of friends or acquaintances who might bring them down. Still other work finds that older adults learn to let go of loss and disappointment over unachieved goals, and hew their goals toward greater wellbeing. 

What's missing, say the authors, are consistently demonstrated direct links between these strategies and phenomena and changes of mood for the better. One reason, Isaacowitz suggests, is that lab tests yield results that are not straightforward. "When we try to use those cognitive processes to predict change of mood, they don't always do so," he explains. "Sometimes looking at positive pictures doesn't make people feel better." A closer review of the literature also reveals contradictions. Some people -- younger ones, for instance -- may make themselves feel better by accentuating the negative in others' situations or characteristics. And whereas some psychologists find that high scores on certain cognitive tests correlate in older people with the ability to keep their spirits up, other researchers hypothesize that happiness in later life is an effect of cognitive losses -- which force older people to concentrate on simpler, happier thoughts. 

More rigorous methods probably won't overthrow the current theories, says Isaacowitz, but they will complicate the picture. "It won't be as easy to say old people are happier. But even if they are happier on average, we still want to know in what situations does this particular strategy make this particular person with these particular qualities or strengths feel good." 

Source: Association for Psychological Science [January 05, 2012]

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Shot of Young Stem Cells Makes Rapidly Aging Mice Live Much Longer and Healthier

Mice bred to age too quickly seemed to have sipped from the fountain of youth after scientists at the University of Pittsburgh School of Medicine injected them with stem cell-like progenitor cells derived from the muscle of young, healthy animals. Instead of becoming infirm and dying early as untreated mice did, animals that got the stem/progenitor cells improved their health and lived two to three times longer than expected, according to findings published in the Jan. 3 edition of Nature Communications. 

Researchers have found that mice bred to age too quickly seemed to have sipped from the fountain of youth after being injected with stem cell-like progenitor cells derived from the muscle of young, healthy animals [Credit: © Vasiliy Koval/Fotolia]

Previous research has revealed stem cell dysfunction, such as poor replication and differentiation, in a variety of tissues in old age, but it's not been clear whether that loss of function contributed to the aging process or was a result of it, explained senior investigators Johnny Huard, Ph.D., and Laura Niedernhofer, M.D., Ph.D. Dr. Huard is professor in the Departments of Orthopaedic Surgery and of Microbiology and Molecular Genetics, Pitt School of Medicine, and director of the Stem Cell Research Center at Pitt and Children's Hospital of PIttsburgh of UPMC. Dr. Niedernhofer is associate professor in Pitt's Department of Microbiology and Molecular Genetics and the University of Pittsburgh Cancer Institute (UPCI). 

"Our experiments showed that mice that have progeria, a disorder of premature aging, were healthier and lived longer after an injection of stem cells from young, healthy animals," Dr. Niedernhofer said. "That tells us that stem cell dysfunction is a cause of the changes we see with aging." 

Their team examined a stem/progenitor cell population derived from the muscle of progeria mice and found that compared to those from normal rodents, the cells were fewer in number, did not replicate as often, didn't differentiate as readily into specialized cells and were impaired in their ability to regenerate damaged muscle. The same defects were discovered in the stem/progenitor cells isolated from very old mice. 

"We wanted to see if we could rescue these rapidly aging animals, so we injected stem/progenitor cells from young, healthy mice into the abdomens of 17-day-old progeria mice," Dr. Huard said. "Typically the progeria mice die at around 21 to 28 days of age, but the treated animals lived far longer -- some even lived beyond 66 days. They also were in better general health." 

As the progeria mice age, they lose muscle mass in their hind limbs, hunch over, tremble, and move slowly and awkwardly. Affected mice that got a shot of stem cells just before showing the first signs of aging were more like normal mice, and they grew almost as large. Closer examination showed new blood vessel growth in the brain and muscle, even though the stem/progenitor cells weren't detected in those tissues. 

In fact, the cells didn't migrate to any particular tissue after injection into the abdomen. 

"This leads us to think that healthy cells secrete factors to create an environment that help correct the dysfunction present in the native stem cell population and aged tissue," Dr. Niedernhofer said. "In a culture dish experiment, we put young stem cells close to, but not touching, progeria stem cells, and the unhealthy cells functionally improved." 

Animals that age normally were not treated with stem/progenitor cells, but the provocative findings urge further research, she added. They hint that it might be possible one day to forestall the biological declines associated with aging by delivering a shot of youthful vigor, particularly if specific rejuvenating proteins or molecules produced by the stem cells could be identified and isolated. 

Source: University of Pittsburgh Schools of the Health Sciences [January 03, 2012]

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Antioxidant has potential in the Alzheimer's fight

When you cut an apple and leave it out, it turns brown. Squeeze the apple with lemon juice, an antioxidant, and the process slows down. 

Simply put, that same "browning" process—known as oxidative stress—happens in the brain as Alzheimer's disease sets in. The underlying cause is believed to be improper processing of a protein associated with the creation of free radicals that cause oxidative stress. 

Now, a study by researchers in the University of Georgia College of Pharmacy has shown that an antioxidant can delay the onset of all the indicators of Alzheimer's disease, including cognitive decline. The researchers administered an antioxidant compound called MitoQ to mice genetically engineered to develop Alzheimer's. The results of their study were published in the Nov. 2 issue of the Journal of Neuroscience. 

According to the Alzheimer's Society, more than 5 million Americans currently suffer from the neurodegenerative disease. Without successful prevention, almost 14 million Americans will have Alzheimer's by 2050, accounting for healthcare costs of more than $1 trillion a year. 

Oxidative stress is believed to cause neurons in the brain to die, resulting in Alzheimer's. Study author James Franklin, an associate professor of pharmaceutical and biomedical sciences, has studied neuronal cell death and oxidative stress at UGA since 2004. 

"The brain consumes 20 percent of the oxygen in the body even though it only makes up 5 percent of the volume, so it's particularly susceptible to oxidative stress," said Franklin, coauthor of the study along with Meagan McManus, who received her Ph.D. in neuroscience from UGA in 2010. 

The UGA researchers hypothesized that antioxidants administered unsuccessfully by other researchers to treat Alzheimer's were not concentrated enough in the mitochondria of cells. Mitochondria are structures within cells that have many functions, including producing oxidative molecules that damage the brain and cause cell death. 

"MitoQ selectively accumulates in the mitochondria," said McManus, who is now studying mitochondrial genetics and dysfunction as a postdoctoral researcher at Children's Hospital of Philadelphia. 

"It is more effective for the treatment to go straight to the mitochondria, rather than being present in the cell in general," she said. 

Although he had not previously conducted research on Alzheimer's disease, Franklin was moved to approve McManus' research proposal to take his laboratory research in a more clinical direction in part because of her family's history with the disease. 

"Two of my grandparents had Alzheimer's disease, but they presented with it very differently. While my granddad often couldn't remember who we were, he was still the same soulful funnyman I'd always loved. But the disease changed my grandmother's mind in a different way, and turned her into someone we'd never known," said McManus. 

"So the complexity of the disease was most intriguing to me. I wanted to know how and why it was happening, and more importantly, how to stop it from happening to other people," she said. 

In their study, mice engineered to carry three genes associated with familial Alzheimer's were tested for cognitive impairment using the Morris Water Maze, a common test for memory retention. The mice that had received MitoQ in their drinking water performed significantly better than those that didn't. Additionally, the treated mice tested negative for the oxidative stress, amyloid burden, neural death and synaptic loss associated with Alzheimer's. 

Source: University of Georgia [December 14, 2011]

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Scientists provide potential explanation for mechanisms of associative memory

Researchers from the University of Bristol have discovered that a chemical compound in the brain can weaken the synaptic connections between neurons in a region of the brain important for the formation of long-term memories. The findings, published in the Journal of Neuroscience, may also provide a potential explanation for the loss of memory associated with Alzheimer's. 

Acetylcholine, a neurotransmitter, is released in the brain and is known to play an important role in normal brain functions such as sleep, attention, and learning and memory. Until now the mechanisms by which this transmitter controls such processes were not well understood. 

The findings, led by researchers from the University's MRC Centre for Synaptic Plasticity in the School of Physiology and Pharmacology, highlight the mechanisms by which acetylcholine controls communication between neurons located in the prefrontal cortex and may help in understanding how higher cognitive processing is controlled in this important brain area. 

Professor of Cellular Neuroscience, Zafar Bashir and his team have demonstrated how electrical stimulation of the prefrontal cortex leads to the release of acetylcholine from synaptic terminals and the subsequent weakening of synaptic connections between neurons. 

When acetylcholine is released it binds to specific receptors and starts a molecular cascade which triggers physiological alterations in how prefrontal cortical neurons are 'wired' together. The findings suggest that the persistent weakening of synaptic connections between neurons induced by the endogenous release of acetylcholine in the prefrontal cortex may underlie the formation of new associative memories. 

The authors speculate that the memory impairments associated with Alzheimer's dementia may result, in part, from a loss of synaptic plasticity in the prefrontal cortex related to the depletion of brain acetylcholine that occurs in the disease. 

Dr Douglas Caruana, who carried out the experiments, said: "Disruptions in cholinergic signaling in the prefrontal cortex are known to affect how the brain encodes lasting associations between objects and places, and a depletion of brain acetylcholine levels in the cortex is a classic hallmark of Alzheimer's dementia'." 

Professor Bashir added: "Acetylcholinesterase inhibitors are the most widely used medication to treat individuals with Alzheimer's dementia and the enhancement of synaptic plasticity by acetylcholinesterase inhibition that we now demonstrate may be a way in which these drugs provide clinical efficacy." 

Source: University of Bristol [December 13, 2011]

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What do animals 'know'? More than you may think

Rats use their knowledge to make decisions when faced with ambiguous situations, UCLA psychologists report.

A rat finds a reward in an ambiguous situation [Credit: Aaron Blaisdell/UCLA Psychology]

"Rats often make judgments and behave as if they're rational creatures," said UCLA associate professor of psychology Aaron Blaisdell, a member of UCLA's Brain Research Institute and senior author of a new study published in the December issue of the journal Psychonomic Bulletin and Review.

"To make a decision in the face of uncertainty, rats call on prior history and reasoning," Blaisdell said. "They apply what they know to a situation where they are uncertain. The rats are not necessarily thinking like little humans, but they have learned through experience. A lot of animal behavior seems to be rational. Their behavior follows logical inferences."


Blaisdell, an expert in animal cognition (he avoids the phrase "animal intelligence"), and Cynthia Fast, the study's lead author and a UCLA graduate student in psychology, report on a series of experiments in which 74 female rats were rewarded with a sugar solution — which rats like about as much as teenagers like soda, Blaisdell said — for pressing a lever under certain conditions but not under others, which they learned to differentiate. 

The rats, none of which were harmed, first learned to expect the sugar reward if they pressed a lever when they saw one of two lights illuminated in their enclosure but not when they saw both lights on. After learning this pattern in 90 days, the rats were shown only one illuminated light while the other light was covered. In this case, the rats searched less for the sugar solution, as if both lights were on. This indicated, Blaisdell said, that the rats imagined the other light to be on, even though they could not see it. 

"Their behavior is consistent with their having an image of the light being on," Blaisdell said. "When we didn't cover the light, they knew what decision to make. They have the ability to hold an image of something that is not there and make a decision based on that." 

"Their prior learning influenced how they perceived this ambiguity," Fast said. "The rats responded less in this condition than they would if there was just a single light but more than they would if both lights were on. It would be like your driving on your commute and approaching an intersection where you know there is a traffic light but you can't see it because a tree branch or a bus in front of you is blocking your view. You approach slowly until you're able to see if the light is red or green. The rats seem to be doing the same thing. It's as if they reason, 'Hmm, I can't see the light on the right; maybe it's on,' and they press the lever less than they would if there were just a single light on."

The research was federally funded by the National Science Foundation.

In another experiment, rats were given the reward only if they pressed a lever when both lights were on, but not when either light was on alone — a pattern they learned much more quickly (in only 30 days). Then the psychologists covered one of the lights to study how the rats would respond. 

What was surprising, they said, was that covering the light in this case did not seem to have any impact on the rats' decision to respond. They continued to behave as if they were certain that the covered light was not on.

 To find out why, the researchers conducted a follow-up experiment in which the rats were again given the reward for pressing the lever when both lights were on (but not when only one was on), and they were also given the reward if they pressed the lever when they heard a tone or a clicking sound — but not the tone and clicking sound simultaneously. Other rats were given the reward only if the tone and clicking sound occurred together, not separately.

"The rats are capable of learning that too," Fast said. "They learn to differentiate among these different lights and different auditory cues and can tell them all apart." 

"It takes them a long time," Blaisdell said.

The rats were more sensitive to ambiguity when the uncertainty followed the more challenging training involving both the lights and the auditory cues, even in the condition that failed to make a difference previously, Fast and Blaisdell report.

"The difficulty of the task the rats are engaged in affects how they deal with uncertainty," Blaisdell said. "When the task is more difficult, they address it in a more sophisticated fashion. As far as I know, that has not been shown with any animal before."

 Little is known about how human imagination works, but an understanding of how widespread imagination is across the animal kingdom can shed light on the origins of imagination,
Blaisdell said. 

The aging brain 

The ability to make decisions in ambiguous situations declines with age, Blaisdell and Fast noted.

"With aging, decision-making becomes more fragile, especially in the face of lack of information," Blaisdell said. 

Blaisdell is interested in learning the brain mechanisms involved in decision-making and perhaps applying this research to human cognition and neural changes that occur with aging or with degenerative diseases. He also hopes to gain new insights into how we learn.

"There is still so much we don't know about learning," he said. "The more we can understand about how the brain supports cognition, the more we will be able to look for where cognition is going wrong when the brain malfunctions." 

Author: Stuart Wolpert | Source: University of California Los Angeles [December 08, 2011]

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Drug reverses aging-associated changes in brain cells

Drugs that affect the levels of an important brain protein involved in learning and memory reverse cellular changes in the brain seen during aging, according to an animal study in the December 7 issue of The Journal of Neuroscience. The findings could one day aid in the development of new drugs that enhance cognitive function in older adults. 

Aging-related memory loss is associated with the gradual deterioration of the structure and function of synapses (the connections between brain cells) in brain regions critical to learning and memory, such as the hippocampus. Recent studies suggested that histone acetylation, a chemical process that controls whether genes are turned on, affects this process. Specifically, it affects brain cells' ability to alter the strength and structure of their connections for information storage, a process known as synaptic plasticity, which is a cellular signature of memory. 

In the current study, Cui-Wei Xie, PhD, of the University of California, Los Angeles, and colleagues found that compared with younger rats, hippocampi from older rats have less brain-derived neurotrophic factor (BDNF) -- a protein that promotes synaptic plasticity -- and less histone acetylation of the Bdnf gene. By treating the hippocampal tissue from older animals with a drug that increased histone acetylation, they were able to restore BDNF production and synaptic plasticity to levels found in younger animals. 

"These findings shed light on why synapses become less efficient and more vulnerable to impairment during aging," said Xie, who led the study. "Such knowledge could help develop new drugs for cognitive aging and aging-related neurodegenerative diseases, such as Alzheimer's disease," she added. 

The researchers also found that treating the hippocampal tissue from older animals with a different drug that activates a BDNF receptor also reversed the synaptic plasticity deficit in the older rats. Because histone acetylation is important in many functions throughout the body, these findings offer a potential pathway to treat aging-related synaptic plasticity deficits without interfering with histone acetylation. 

"It appears that lifelong shifts in gene regulation steadily deprive the brain of a key growth factor and cause a collapse of the 'machinery' supporting memory, cognition, and the viability of neurons," said Gary Lynch, PhD, a synaptic plasticity expert at the University of California, Irvine. "The very good news suggested by this study is that it may be possible to reverse these effects." 

Source: Society for Neuroscience [December 07, 2011]

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Study Looks at the Nature of Change in Our Aging, Changing Brains

As we get older, our cognitive abilities change, improving when we're younger and declining as we age. Scientists posit a hierarchical structure within which these abilities are organized. There's the "lowest" level -- measured by specific tests, such as story memory or word memory; the second level, which groups various skills involved in a category of cognitive ability, such as memory, perceptual speed, or reasoning; and finally, the "general," or G, factor, a sort of statistical aggregate of all the thinking abilities. 

What happens to this structure as we age? That was the question Timothy A. Salthouse, Brown-Forman professor of psychology at the University of Virginia, investigated in a new study appearing in an upcoming issue of Psychological Science, a journal published by the Association for Psychological Science. His findings advance psychologists' understanding of the complexities of the aging brain. 

"There are three hypotheses about how this works," says Salthouse. "One is that abilities become more strongly integrated with one another as we age." That theory suggests the general factor influences cognitive aging the most. The second -- based on the idea that connectivity among different brain regions lessens with age -- "is almost the opposite: that the changes in cognitive abilities become more rather than less independent with age." The third was Salthouse's hypothesis: The structure remains constant throughout the aging process. 

Using a sample of 1,490 healthy adults ages 18 to 89, Salthouse performed analyses of the scores on 16 tests of five cognitive abilities -- vocabulary, reasoning, spatial relations, memory, and perceptual speed. The primary analyses were on the changes in the test scores across an interval of about two and a half years. 

The findings confirmed Salthouse's hunch: "The effects of aging on memory, on reasoning, on spatial relations, and so on are not necessarily constant. But the structure within which these changes are occurring does not seem to change as a function of age." In normal, healthy people, "the direction and magnitude of change may be different" when we're 18 or 88, he says. "But it appears that the qualitative nature of cognitive change remains the same throughout adulthood." 

The study could inform other research investigating "what allows some people to age more gracefully than others," says Salthouse. That is, do people who stay mentally sharper maintain their ability structures better than those who become more forgetful or less agile at reasoning? And in the future, applying what we know about the structures of change could enhance "interventions that we think will improve cognitive functioning" at any age or stage of life. 

Source: Association for Psychological Science [November 22, 2011]

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Biologists slow the aging process... in fruit flies

UCLA life scientists have identified a gene that slows the aging process. The biologists, working with fruit flies, activated a gene called PGC-1, which increases the activity of mitochondria, the tiny power generators in cells that control cell growth and tell cells when to live and die. 

"We took this gene and boosted its activity in different cells and tissues of the fly and asked whether this impacts the aging process," said David Walker, an assistant professor of integrative biology and physiology at UCLA and a senior author of the study. "We discovered that when we boost PGC-1 within the fly's digestive tract, the fly lives significantly longer. We also studied neurons, muscle and other tissue types and did not find life extension; this is telling us there is something important about the digestive tract." 

The research appears in the current online edition of Cell Metabolism, the leading journal in its field, and will be published in an upcoming print edition. Co-authors are from Walker's laboratory, the Salk Institute for Biological Studies in La Jolla, Calif., and the department of biology at UC San Diego. 

"By activating this one gene in this one tissue — the intestine — the fly lives longer; we slow aging of the intestine, and that has a positive effect on the whole animal," said Walker, a member of UCLA's Molecular Biology Institute. "Our study shows that increasing PGC-1 gene activity in the intestine can slow aging, both at the cellular level and at the level of the whole animal." 

The biologists delayed the aging of the flies' intestines and extended their lives by as much as 50 percent. 

Fruit flies, or Drosophila melanogaster, have a life span of about two months. They start showing signs of aging after about one month, and they slow down, become less active and die, Walker said. They are a great model for studying aging, he said, because scientists know every one of their genes and can switch individual genes on and off. 

What are the study's implications for human aging? 

"We all think about protecting the brain and the heart, but the intestine is a vital tissue type for healthy aging," Walker said. "If anything goes wrong with the mitochondria in cells, the consequences could be devastating, and if anything goes wrong with our intestines, that may have devastating consequences for other tissue types and organs. Not only is the intestine essential for the uptake of nutrients that are a vital source of energy, but it is also an important barrier that protects us from toxins and pathogens in the environment. The intestine has to be well-maintained. 

"No one yet knows what causes aging at the cellular or tissue level," Walker said. "As we age, our mitochondria become less efficient and less active. That has far-reaching consequences, because if the mitochondria decline, then all of our cellular functions may be compromised. However, it's a dangerous road to travel to say, 'This is the cause of aging.'" 

The PGC-1 gene activates the cells' mitochondria and regulates mitochondrial activity in mammals and flies. The gene is a potential target for pharmaceuticals to combat age-related diseases, Walker said. 

The study raises the question of whether increasing mitochondrial activity is an effective strategy to delay aging. If so, increasing the PGC-1 gene may prove key, Walker said. 

The first question Walker and his colleagues asked was whether the fruit fly version of PGC-1 has the same function as the mammalian version. They found it does. 

The biologist increased levels of expression of the fly version of the PGC-1 gene and found that this made mitochondria more active. They then tested whether boosting PGC-1 activity would slow aging and, again, they found that it did, when they focused on the fly's digestive tract. 

The fly's intestine is maintained by adult stem cells, previous research has shown. The biologists also asked what would happen if they used genetic and molecular tools to boost PGC-1 gene expression within only the stem cells and their immediate "daughter" cells. 

"Collaborating with a stem cell group at the Salk Institute for Biological Studies, we boosted the gene expression within just the stem- and the immediate daughter-cell types and found that was sufficient to extend the life span of the flies," said Walker, who studies the basic underlying mechanisms of the aging process. 

In addition, increasing the fruit fly's version of PGC-1 delays the onset of cellular changes within the intestine, thereby establishing a link between mitochondria, tissue stem cells and aging, the new study shows. 

"Many scientists study the diseases of aging, and they tend to do so individually," Walker said. "One group will study Alzheimer's disease, another group will study cardiovascular disease, another will study cancer. We take a different approach. We don't single out any of these specific diseases of old age. We study the aging process itself. Aging is the No. 1 risk factor for most cancers, heart disease, Alzheimer's disease, Parkinson's disease and many others."  

Source: University of California - Los Angeles [November 08, 2011]

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