Roughly 30 million Americans suffer from migraines, and as you might expect, there’s a large pharmaceutical market to prevent or stop these debilitating headaches. Drugs such as Imitrex and Verapamil employ different pharmacological modes of action, reducing migraines by adjusting neurotransmitter levels, blocking ion channels, or simulating the body’s natural painkillers. There’s also a less pharmaceutical migraine treatment strategy, recommended by many headache specialists, that follows the old adage: “Active Body, Active Mind.” One recent study even found that 40 minutes of exercise three times a week can be as effective at preventing migraines as popular anti-migraine medications.

Still, prescribing exercise or environmental enrichment (keeping the mind busy through activities such as reading, crossword puzzles, exercise, or socialization) can strike some doctors and patients as frustratingly vague. Understanding the biological mechanism that makes these activities protective against migraines could help convince doctors and patients of their utility, while also giving researchers the opportunity to translate the factors associated with environmental enrichment into highly effective treatments.  In the laboratory of Richard Kraig, William D. Mabie Professor in the Neurosciences at University of Chicago Medicine, that very effort is underway.

“We are interested in environmental enrichment as a way to stop cognitive decline from aging, injury after stroke, Parkinson’s disease, and cell death after seizures.  With our new work, we apply this search for how the brain protects itself against disease to include migraines,” Kraig said.  ”The ‘why’ of it has sometimes been left in the realm of holistic medicine, with little scientific support.  So establishing the hard science makes it more credible to the psychologists, physiologists, physiatrists, because here’s the chemistry.”

Working with graduate students Yelena Grinberg and Aya Pusic as well as senior technician Heidi Mitchell, Kraig discovered three different natural signals elevated by exercise and environmental enrichment: insulin-like growth factor-1 (IGF-1), interleukin-11 (IL-11), and interferon gamma (IFN-γ). When these “cytokines” are applied to brain slices, they reduce the probability of triggering a spreading depression — a transient wave of reduced brain activity associated with migraines. Understanding how those cytokines stop spreading depression — and the nasal route by which they might be delivered — may revolutionize how migraines and other neurological conditions are treated.

A spreading depression of brain is a chain reaction of dramatic events. After an initial burst of increased neuronal activity, a subsequent ripple of absent activity slowly spreads across involved brain at a rate of about 3 mm per minute — lasting a few minutes overall.  While the event sounds brief, the consequences can last from hours to days, causing harmful oxidative stress, elevated inflammatory factors, moving microglia, and significant pain and discomfort for the migraine sufferer.

Paradoxically, the way to stop this chain reaction may not be to simply reduce or block the byproducts of a spreading depression, but to expose the brain to moderate levels of inflammatory factors, which include the cytokines described above. To interrupt the cycle of repeated migraines, treatments could take place before the process begins or in small steps after the recurrent spreading depression that underlies chronic migraine. While these factors may have negative effects in the short-term, in the long-term they prime the neurons to make antioxidants that are protective against oxidative stress.

“Spreading depression increases oxidative stress in a big fashion — it depolarizes all the brain cells. It’s like an engine kicking out a lot of exhaust, and the exhaust makes the brain hyper-excitable,” Kraig said. “But you have to let the engine run. The engine is running with stimuli that include cytokines that are initially irritative, but then adapt to stop spreading depression.”

The trick, Kraig said, is to mimic the natural cycles of cytokine levels the brain would experience during healthy, active behavior, rather than drowning the system in abnormally high concentrations of the factors that can occur with disease. The cytokines would be delivered to the brain in an on/off pattern rather than chronically, theoretically recreating the rise and fall of natural cytokines during a person’s sleep/wake cycle. By giving just a little bit of a factor normally considered harmful, the treatment could strengthen the brain’s resistance to spreading depression and migraines via the principle of hormesis, or “what doesn’t kill me makes me stronger.”

“The treatment is unique in that it’s the opposite of putting a Band-Aid on something,” Grinberg said. “It’s triggering cells to produce their own antioxidants instead of just providing the antioxidants exogenously. In that way it’s really unique and the opposite of how a lot of people think about medical treatment.”

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By Matt Wood

Joseph Kirsner, MD, continues to report to work after 76 years as a gastroenterologist at the University of Chicago Medical Center. At 102, he must be doing something right. Sure, he keeps his mind and body active by keeping up with research and coming into the office. But how much of longevity is attributable to a healthy lifestyle and good genes, and how much is due to luck?

Two researchers at the Center on Aging at the University of Chicago have found that luck plays a significant role in living to 100. In a new study published in The Journal of Aging Research, they found that people born in September, October or November had higher odds to crack the century mark than those born in the spring.

Leonid Gavrilov, PhD, and his colleague and wife, Natalia Gavrilova, PhD, look for clues to longevity at the Center on Aging, which is part of NORC at the University of Chicago. They study potential predictors and determinants of human longevity, such as family background and environment. “It’s a way to get insights into mechanisms of aging and longevity, and hopefully to find new approaches to extend healthy human life,” Leonid Gavrilov said.

In past studies they found that chances for exceptional longevity are higher for U.S. citizens who were born to young mothers, had a slender or medium body build at age 30 and were farmers or spent their childhood on a farm. Studying pooled data about longevity for large populations can be tricky though.

“People from families with different ethnic, educational and income background may have somewhat different chances for long life,” Natalia Gavrilova said. “Also, different families may have slightly different seasonal patterns of births, because of religious and cultural traditions, holidays and vacation preferences.”

To control for unobserved differences between families in their latest study, they used a “within-family” approach by studying differences in life span between siblings within the same families, with the same parents and family background. They also studied spouses in the same families who lived together and shared their living conditions at adult age.

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Have you ever cheated on a test by glancing over at someone else’s work? Or relied on a fellow student to carry the load on a group project while you coast along with minimal effort? While few will admit to these forms of cheating, they have long been fixtures of the classroom. However, a lazy individual benefiting from the hard work of a colleague is not a trick exclusive to humans. In a recent study of bacterial infections in plants, the laboratory of evolutionary biologist Joy Bergelson demonstrated that these unsavory practices can also be found in pathogens - and that may be a good thing for us.

In the bacterial world, the goal is survival. What we perceive as an infection is merely colonization for the bacterial population, who are establishing a new home where they can happily feed off the host’s nutrients and reproduce. Bacteria build and release virulence factors to achieve this settlement and evade immune system defenses. But because these factors spread out, benefiting an individual bacterium’s neighbors as well as itself, a sneaky bacterium can get by without producing its own virulence factors. In laboratory dish experiments, scientists observed that bacteria engineered without the ability to release factors can still thrive so long as they are paired with normal, pathogenic partners.

Though scientists described this “cooperator-cheater model” in the artificial environment of the dish, nobody had yet observed it in a natural setting. For a study published in September by the journal Ecology Letters, a team led by postdoctoral fellow Luke Barrett discovered the model in action within the cells of the popular genetic model plant Arabidopsis thaliana.

“We’re showing that cheating actually happens in nature, and that the cheaters persist,” Bergelson said. “You can make cheaters that do well in the lab, and you can show that these systems may be stable in theory, but to show that it is actually happening in nature is novel.”

Recently, researchers discovered that Arabidopsis carried two strains of the bacteria Pseudomonas syringae, a common plant pathogen. While one strain had all the normal pathogenic activity, another was a kind of bacterial pacifist, with a broken system for secreting virulence factors. Surprisingly, these two strains appear with almost equal frequency in Arabidopsis, suggesting that the non-pathogenic strains are far more successful in nature than previously thought.

To test the nature of this relationship, researchers took the two natural strains and experimentally infected plants with only one or the other. When grown alone, the “cheater” strain was not nearly as successful without its more aggressive partner around to unwittingly “donate” virulence factors. Additional modeling suggested that the more aggressive the virulent strain, the more likely it was that cheaters would be found nearby eager to exploit the hard work of their pathogenic peers. The cheater strains are also harder for the host immune system to spot, since the machinery that produces and releases virulence factors is a frequent target of those defenses.

“When you go into the field, it’s kind of a curiosity: why would non-pathogenic cheaters be almost as common as pathogens inside the host?” Bergelson said. “It turns out that the cheaters can do really well as long as they’re with the pathogenic variety, and they don’t pay the price of having to actually make a secretion system or effectors. They also don’t run any risk of being recognized because it is the presence of secreted effectors that causes the recognition events in the first place. So, these non-pathogens have some good things going for them.”

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The future of genetic medicine comes in many flavors, from the discovery of the rare mutations responsible for uncommon diseases to the cataloging of variants that may be responsible for common diseases such as high blood pressure and diabetes. A segment from last night’s ABC 7 Chicago news focused on both aspects of this potential, jumping from a young man in Utah with Miller Syndrome to the 1200 Patient Project of the Medical Center’s Mark Ratain and Peter O’Donnell. Results from the project, currently underway, could help physicians customize medical treatments for individual patients, maximizing effectiveness while reducing side effects. As the segment says, if we really are heading toward a future where every patient has their genetic code read as routinely as they receive a doctor’s check-up, such research will be essential for unleashing the power of genetic medicine.

When the media hypes the healthy effects of drinking red wine in moderation, they’re talking about resveratrol, the chemical responsible for wine’s benefits. Scientists have long tested whether isolating that chemical can turn it into a super-pill for good health and long life without the alcoholic “side effects” of its normal route, with mixed results. But a new study featured in the New York Times this morning finds an intriguing benefit of a resveratrol derivative called SRT-1720. Obese mice given the experimental drug lived 30 percent longer - as long as control mice - rather than expiring earlier from obesity-related diseases such as fatty liver and diabetes. As the article states, such a drug may represent “more a moral hazard than an incentive to good health,” seen by some as a way of avoiding the consequences of excess. But with trials of the drug in humans still in their earlier stages, the ethical discussions will have to wait on the science.

Since our piece remembering famed bio-statistician Paul Meier ran last week, two more fine obituaries of the UChicago professor emeritus have appeared. Read the Chicago Tribune take to learn what instrument Meier learned to play at the Old Town School of Folk Music, and the New York Times version for the context of how Meier changed randomization in clinical trials forever.

Living shoulder to shoulder (or even closer, on the subway) in an urban environment feels like a particularly modern phenomenon. But as friend of the blog Tim de Chant explains in his guest blog at Scientific American, human societies have concentrated themselves since even the prehistoric hunter-gatherer days. For more of Tim’s great writing on the science of population density, visit his Per Square Mile blog.

Stress can have all sorts of negative effects on your health, but what about the stress of your spouse or partner? Not Exactly Rocket Science looks at a study in finches that suggests a high-strung life mate could actually shorten your life.

The odds of acquiring a disease are often portrayed as a tug of war between two foes: genes and environment. The battle is not always evenly matched. A disease such as cystic fibrosis is entirely genetic - if a child inherits the mutated CFTR gene from both parents, no environment will prevent the condition. On the other hand, environment can trump genetics for many other diseases, such as the relationship between exposure to the toxic substance arsenic and the cancer mesothelioma. But in most places, the tug of war is a more balanced contest, with the genetic factors controlling risk competing with a range of environmental factors from diet and exercise to education and climate.

Scientists have traditionally kept score on these competitions using a measure called heritability, the percentage of a phenotype (a disease or characteristic) that is determined by genetic factors. One way to measure heritability is with twin studies, which assemble data from thousands of pairs of identical or fraternal twins as a natural experiment of whether genes or environment win out. But a new study from University of Chicago psychiatry researchers shows that the blanket term of “environment” does not have to mean things outside the body - it can also refer to the biological state inside the body.

For the paper, published last month in Behavioral Genetics, a team led by post-doc Terrie Vasilopoulos set out to test the relationship between two health conditions: hypertension and cognitive decline. Previous research examining this link established hypertension as a risk factor for the loss of cognitive ability late in life, producing decreases in performance similar to those seen in Alzheimer’s disease and other forms of dementia. Meanwhile, heritability research revealed that genetics play a large part in a person’s risk of cognitive decline in their golden years. So does the “internal environment” of hypertension - and whether it is treated - move the tug-of-war of heritability for cognitive issues toward genes or environment?

To test this hypothesis, the team used data from the Vietnam Era Twin Study of Aging - over 1,200 male-male twin pairs who served in the military between 1965 and 1975. With an age range between 51 and 60, the researchers looked at an important time in a man’s cognitive lifetime before the first signs of dementia typically set in, Vasilopoulos said.

“We really think we are capturing a very important developmental period with the guys that we’re studying, especially for cognitive phenotypes,” said Vasilopoulos, a researcher in the laboratory of Kristen Jacobson, assistant professor of psychiatry. “The groundwork for these bad things that are happening to you later in life are being laid when you’re much younger. By finding these mechanisms early in life, we can start to figure out better game plans of trying to protect people and help people make smarter choices when younger so we don’t see these bad effects when they’re older.”

The men were divided into three groups: those with hypertension receiving treatment, those with untreated hypertension, and those without hypertension. On overall measures of cognitive ability, the three groups showed no differences in performance, suggesting that the researchers were indeed looking at an age before any noticeable decline begins. But when the heritability of different cognitive measures was examined, a relationship with hypertension and anti-hypertension medication emerged.

For two measures - episodic memory and visual-spatial ability - the heritability of how a person performed on the tests actually decreased in those with untreated hypertension, relative to the other two groups. That is, in men with high blood pressure not taking medication, the “internal environment” of the disease outweighed the influence of genetics on two early warning signs of cognitive problems.

“These are the two types of cognitive domains that are first affected by age-related cognitive decline,” Vasilopoulos said. “In Alzheimer’s disease or other types of neurodegeneration or just regular aging, those are the most affected or first affected. So we really think we are honing in on the mechanisms of why hypertension is bad for cognitive performance late in life.”

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By Dianna Douglas

More research practically begging people to get a good night’s sleep has come out of the sleep labs at the University of Chicago. Eve Van Cauter and Rachel Leproult have discovered that a week of inadequate sleep means less testosterone in young men.

A lot less.

In the study, ten healthy young men gave blood samples after a week of sleeping just five hours a night. By the end of the week, they had 15 percent less testosterone than normal. “This is not an insignificant amount, since it is about the amount that occurs with normal aging by 10 to 15 years,” Van Cauter said. As a man ages, testosterone production decreases by 1 to 2 percent a year.

The lack of testosterone affected not only the reproductive function of these young men, but their happiness as well. Testosterone is a vital hormone for a man’s physical and mental health, and is released into the body during sleep.

“Low testosterone levels are associated with reduced well being and vigor,” Van Cauter said, explaining why the young men said they felt grumpy and lethargic, and their mood worsened as the study progressed.

Low testosterone is associated with low energy, reduced libido, and poor concentration. Consumer Reports Health found in a recent survey that feeling too tired is the reason men cite most often for a low sex drive.

This isn’t just a lab exercise - sleep loss is endemic in modern society. At least 15 percent of the adults in the US get less than 5 hours of sleep a night. Shift workers are especially at risk for lost sleep. The average American got nine hours of sleep in 1910 and got seven in 1975. The cumulative effects of short sleep are still being discovered, and they’re all bad. People who don’t get enough sleep are fatter, more likely to have diabetes, have all sorts of learning and cognitive problems, and die earlier. Van Cauter says that a nation that doesn’t sleep enough has an epidemic of obesity and diabetes.

“As research progresses, low sleep duration and poor sleep quality are increasingly recognized as endocrine disruptors,” Van Cauter said. Mess with the delivery of hormones throughout the body, and people become hungrier and sadder. Their blood pressure goes up and their insulin production goes haywire.

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There’s no denying that preventive medical screens do save lives, whether through mammograms, colonoscopies, or prostate exams. But for all the benefits, screening is not a one-size-fits-all practice. In the case of prostate cancer, mortality rates have declined by more than 30 percent in the last 20 years as testing levels of prostate-specific antigen (PSA) became a common clinical screen in older men. But other studies of the benefits of PSA screening have been less decisive, including a large 2009 study that found no difference in cancer-specific mortality over the last 10 years. Why the discrepancy?

One answer is that the benefit of PSA screening changes with age - and the reduced life expectancy that comes with age. Though 1 in 6 men will be diagnosed with prostate cancer at some point in their lives, many older men diagnosed with prostate cancer die of something other than the disease. Screening elderly men who already have serious health problems can therefore do more harm than good, paving the way for invasive procedures, risky treatment, anxiety, and health care costs that may have been unnecessary. As a result, many clinical panels have recommended that PSA screening should only be conducted in men younger than 75 or men with at least 10 years of estimated life expectancy due to old age or health problems.

But recommendations do not always match up with practice. To measure the true screening patterns in the clinical setting, a team including Scott Eggener, assistant professor of surgery at the Medical Center, broke down the numbers from a huge national health survey. The data , published this week in the Journal of Clinical Oncology, showed a quite different shape than many would hope: rather than a bell curve with the highest screening rates appearing in men 55-69 who benefit the most, the curve is an uphill climb to a plateau, with men in their 70s receiving the most tests. Men aged 70 to 79 were screened for PSA at almost twice the rate of men aged 50 to 54.

“Our findings show a high rate of elderly and sometimes ill men being inappropriately screened for prostate cancer,” Eggener told John Easton. “We’re concerned these screenings may prompt cancer treatment among elderly men that ultimately has a very low likelihood of benefiting the patient and paradoxically can cause more harm than good.”

When measured according to life expectancy, the results were not much better. Roughly 750,000 men with an estimated life expectancy of 5 years - half of the recommended 10 years - received PSA screening in the previous year.

“The men most likely to benefit from PSA screening are paradoxically being screened at markedly lower rates than men highly unlikely to benefit,” the authors wrote.

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Welcome to pilot episode 2 of our Medical Center research news podcast. We’re keeping the water wings on for now as we continue to refine the format and discover all the technical struggles inherent in podcasting, but please do listen and give us feedback on how we’re doing - and if you have good ideas for a name.

In this episode, we talk to J. Martin Leland about the Stay in the Game event and preventing injuries for baseball, golf, and tennis season. Dianna Douglas reports on the oldest patient to ever receive Whipple surgery at the University of Chicago Medical Center, talking with Kevin Roggin and William Dale about the procedure. And Rob Mitchum reports from a news conference held last weekend by Sen. Dick Durbin about the impact of potential cuts to the National Institutes of Health budget currently being debated in Congress. Thanks for listening!

University of Chicago Research Podcast Episode #0.2 by robmitchum

[If you missed episode 0.1, you can listen here.]

Stacey Sandbo and Stacy Lindau counsel a patient at the PRISM clinic. (Photo by David Christopher)

If your oncologist is worried about your sex life, you’re probably a man.

Stacy Lindau, associate professor of obstetrics/gynecology and geriatrics, has been researching how often women get help for sexual problems after surviving cancer, and the data are grim. Almost none of the women in her study got treatment, and half of them said they wanted it.

Breast or gynecologic cancer is rough on a woman’s sexuality. It often means hormone treatments, chemotherapy, or surgical disfigurations. Cancer could take a breast, the ovaries, or most of the reproductive tract.

Typical results: severe pain during sex, dryness, and difficulty with arousal and orgasm. A mastectomy or hysterectomy will often leave scars that make a woman feel less feminine and attractive. Add that to frequent bladder infections or incontinence after sex, and women find they’re facing some complex problems in bed after cancer. Sometimes the problems persist for years.

Despite abundant research about the negative effects of breast and gynecologic cancers on a woman’s sexuality, a 2002 survey found that physicians generally do not discuss it with their patients. This is in stark contrast to prostate cancer, Lindau said, where men and their doctors talk early and often about preserving sexual function. The dialogue usually begins as soon as a man is diagnosed with prostate cancer, and continues through treatment and beyond.

Lindau, who made national headlines in 2007 by telling Americans about the active sex lives of senior citizens, surveyed hundreds of survivors of breast and gynecological cancer for a study published in Cancer. She asked them who wanted a physician’s advice for sexual problems. Forty-eight percent of young cancer survivors said they did. Interest peaked in women between 48 and 55 - over 52 percent.

It dropped to a fifth among the women over 65. Still, that’s a lot of older women wishing a physician would explain to them why their sex life stalled after cancer and how to get their groove back.

So if women want this help from their physician, why aren’t they asking for it?

One reason is that patients overwhelmingly prefer for their doctor to initiate the discussion. That, however, is a can of worms that physicians won’t open without somewhere to refer their patients for treatment.

“There are few clinics in the United States with the expertise to treat sexual problems in women and girls with cancer,” Lindau said. The University of Chicago has the only one in Illinois, and one of few in the country - the PRISM clinic (Program in Integrative Sexual Medicine for Women and Girls with Cancer).

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“If sleep does not serve an absolutely vital function, then it is the biggest mistake the evolutionary process ever made.” - Allan Rechtschaffen.

We spend approximately one-third of our lives asleep, and yet there is still much to learn about why. Modern sleep research only began less than a century ago, when Nathaniel Kleitman founded the world’s first sleep laboratory at the University of Chicago in 1925. Since then, many of the mysteries of sleep have been uncovered by UChicago researchers, including the discovery of REM sleep by Kleitman and Eugene Aserinsky in 1953, and the characterization of the first sleep disorder, narcolepsy, by Rechtschaffen and Gerry Vogel in the early 1960’s.

But in the last two decades, the study of sleep has shifted from how it works and doesn’t work to the serious consequences when sleep is lacking. Locally, the hub of this new wave of sleep research is Eve Van Cauter, who has linked insufficient or irregular sleep to a long list of chronic diseases including diabetes, obesity, and heart disease. Earlier this week, Van Cauter was doubly honored in receiving the Frederick H. Rawson Professorship and headlining the christening of the new University of Chicago Sleep, Metabolism, and Health Center (SMAHC, pronounced “Smack”). Sleep scientists from UChicago, Northwestern University, and Harvard University gathered to discuss the latest evidence on just how important sufficient sleep is for good health. The consensus message was frightening: From infancy to the golden years, the failure to get a good night’s sleep can cause a wide variety of problems - and may be a major contributor to today’s most worrisome health trends.

The importance of sleep starts with birth, said David Gozal in his talk, and maybe even before due to epigenetic imprinting during the mother’s pregnancy. Gozal reviewed his paper from last month on the elevated risk of obesity in children with shorter and less consistent sleep patterns, but also presented even newer findings, including altered expression of metabolic genes in children who snore and mouse studies that found frequently-disrupted sleep can cause animals to ingest more food and retain more fat tissue. Meanwhile, more and more studies are finding that young children are not getting nearly as much sleep as recommended.

“Sleep curtailment is not only a problem of our adult society, but clearly has pervasively infiltrated to infants and young toddlers,” Gozal said.

The effect of poor sleep upon children may go beyond metabolic issues such as obesity and diabetes, proposed neurobiologist Daniel Margoliash. In both humans and birds, Margoliash’s laboratory has found evidence that sleep helps the brain consolidate information learned during the day into memory. As young birds sleep after a day of practicing their distinctive song, the brain recreates its activity patterns from those earlier performances, presumably part of the process of making that newly learned skill permanent. For schoolchildren, the lesson is clear: lose out on sleep, and you could be losing what you were taught during the preceding day.

Later in life, the problems associated with insufficient sleep only appear to grow worse. In older adults, chronic insomnia has been linked to cognitive decline, perturbations in hormones associated with hunger, and insulin sensitivity, said Northwestern’s Phyllis Zee. Women with polycystic ovary syndrome, a condition marked by infertility, hormonal dysregulation, obesity, and diabetes, are more than 8 times more likely to suffer from obstructive sleep apnea, said David Ehrmann. And the medical effects of poor sleep can literally appear overnight - Vineet Arora’s study of poor sleep in noisy hospital wards found an average blood pressure increase of 6.2 mmHg for every hour of sleep lost. read more

Even before the very rules of life were changed by the discovery of an arsenic-based microbe in a California lake (or were they? More next week.), this week seemed to be full of strange and interesting science involving animals. While ScienceLife works on a bunch of research that is under embargo until later this month (disclaimer: none of them involve extraterrestrial life), here are a few bullet-pointed studies that inspired awe and wonder this week.

• Optogenetics is the technique of creating mutant mice with cells that can be modulated with flashes of light, which is awesome. For example, a scientist can introduce a gene into a mouse strain that makes motor neurons sensitive to light, and when light is shined at those neurons, the mouse starts running. Now, researchers from Stanford and UT Southwestern have used optogenetics in the frontal cortex of a mouse strain, and found a way to produce anti-depressant-like effects (pdf). As covered by David Dobbs at Wired, the technique may offer a new non-invasive way of treating depression way down the line; for now, optogenetics requires a brain implant, which is less than ideal clinically.

• Telomeres, the long repeated sequences at the end of chromosomes, were a fashionable scientific buzzword before optogenetics was even a glimmer in science’s eye. With their companion enzyme telomerase, telomeres were hyped to be the genetic key to the  “fountain of youth,” the biological source of the cell damage that accompanies aging. But despite being the subject of last year’s Nobel Prize in Physiology or Medicine, the excitement about telomeres seemed to have faded out. But an exciting new study published in Nature this week may reignite that flame, as scientists at Harvard reversed the premature aging of a special mutant mouse with telomerase treatment. Wired, Ars Technica, and the Wall Street Journal discussed this “Ponce de Leon” effect, but Discover blog 80beats urges patience for those waiting on anti-aging pills.

• Scientists have long used animal models to study the neurobiology of fear in laboratory settings. But how do you realistically recreate situations that would cause a rat to be scared in the wild in the predator-free world of the animal facility? For one group of scientists, the answer was Robogator, a simulated predator designed to leap out at rats as they moved foraged for food in their lab environment (you can download video clips here). Researchers looked at how close the rat would approach Robogator before and after a lesion of the amgydala, a brain region thought to be involved in fear response. Before the lesion, the rats would only get food 10 inches or less from the entrance to their chamber, but after the lesion, they would go as far as 50 inches, sometimes even approaching and investigating the robot (video) without fear.

• Here’s a novel effect of environmental pollution upon wildlife: when ibis birds of South Florida are exposed to the most potent form of mercury, they opt for homosexual pairings over heterosexual matches.

Scott Brady speaks at the Chicago Biomedical Consortium symposium, Oct. 29, 2010. (photo courtesy of the CBC)

Proteins are a little like laundry: folding matters. When folded properly, proteins can go about their intended business as the machinery of the cell, responsible for its structure and function. A misfolded protein or two can be an annoyance, temporarily throwing off the order of the cell but easily handled by a cell’s internal janitors. But when those misfolded proteins pile up like rumpled clothes across a messy room, the whole system can collapse, leading the cell to an early demise.

These catastrophic failures of folding may be the cause of neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Huntington’s, and Lou Gehrig’s Disease (amyotrophic lateral sclerosis). When pathologists look at the brains of people who die from these conditions, they find unusual changes, with missing neurons and/or abnormal deposits known by names like plaques, tangles, and Lewy bodies. As imaging techniques have improved, scientists have traced these abnormalities back to protein misfolding, with the accumulated defects leading to intracellular traffic jams and even cell suicide.

Experts in the protein folding field met October 29th at the University of Chicago as part of a special symposium organized by the Chicago Biomedical Consortium, a partnership between Chicago-area research institutions. A succession of experts talked about the intricate origami of folding polypeptide structures into functional proteins, the cellular mechanisms that help regulate that process, and the consequences when those mechanisms fail and misfolded proteins are allowed to aggregate into dangerous clumps.

“The ability of polypeptide chains in vivo to fold correctly into their native states with sufficient frequency for them to be able to execute their functions in a living organism is one of the most fundamental and remarkable phenomenons in biology,” said Sangram Sisodia, professor of neurosciences at the University of Chicago. “Despite these regulatory systems, protein misfolding and aggregation do occur, particularly as organisms age, and cause devastating diseases.”

Scott Brady of the University of Illinois at Chicago illustrated those diseases with the famous people they are associated with: Muhammad Ali and Parkinson’s disease, for example, or Woody Guthrie and Huntington’s. Brady then outlined the reasons why a pile of misfolded proteins can be so troublesome to neurons - many of which are long, skinny structures (as long as a meter in humans) that must transport proteins from one end to the other. Should an aggregate of erroneous proteins occur anywhere along that long stretch, it could cause a traffic jam fatal to the cell. Brady’s laboratory has repeatedly demonstrated this process in what is, thanks to their long, wide axons, a favorite animal model of neurobiologists: the squid.

“You may be wondering what calamari has to do with all this,” Brady said. “No, squids do not get Alzheimer’s disease, but they react to the toxic proteins in Alzheimer’s just as well as mammalian systems.”

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Dr. William Dale talks with a patient in his geriatrics clinic (photo by Bart Harris)

Creating a new research field doesn’t happen overnight. It requires bringing together like-minded researchers willing to push out into the unknown, funding agencies willing to be convinced that the new field is worth of grant dollars, and some semblance of an overall plan so that those efforts and dollars are put to optimal use. Soldering together a new field out of two existing fields can save some of the groundwork, but also creates its own set of obstacles, as representatives from each pre-existing discipline maneuver for common ground with their colleagues from across the fence.

The very young field of geriatric oncology, the study of cancer and cancer treatments in the elderly, has already jumped some of those hurdles. Most importantly, the field has a very good reason to exist, as cancer is primarily a disease of the elderly, and the U.S. population is growing increasingly older as baby boomers reach retirement age. Clinics focused on the care of elderly patients with cancer have sprung to life, including the SOCARE Clinic at the University of Chicago Medical Center. Yet there remains a void of knowledge about how cancer forms, grows, and can potentially be cured in older patients, due to clinical trials that enroll primarily younger subjects. Filling that void - and creating a field to do so - was the focus of a two-day conference last weekend at the Hilton O’Hare, where 50 members of the newly-formed Cancer & Aging Research Group discussed the fine details of how best to proceed.

Two numbers presented by NYU’s Daniel Gardner and echoed by several others demonstrated the need for geriatric oncology research: 61 percent of new cancer cases occur in people older than 65, but only 25 percent of patients on cancer clinical trials are from that age group. What’s more, the elderly that do make it into trials of new drugs and therapies are a special breed - “Olympic athletes” that meet strict enrollment requirements designed to pick research subjects that are largely free of co-morbid health conditions beyond their cancer. That leaves physicians in the dark about how to treat less healthy elderly cancer patients, with no evidence to guide their treatment decisions.

“For the vulnerable and frail adults, there’s so little data…it’s a really big population that’s coming to the clinic right now, where almost every patient I see I don’t have the right kind of evidence for,” said Supriya Mohile from the University of Rochester, who organized the conference with Arti Hurria from City of Hope Hospital in California and William Dale, section chief of geriatrics and palliative medicine at the University of Chicago.

One central question of the conference was whether to remedy that shortage by designing clinical trials specifically for older patients or by lobbying clinical researchers to include more elderly subjects in trials. Both solutions hinge upon improving recruitment rates for elderly patients, the burden of which often falls on the researchers themselves. In a talk titled “We Have Met the Enemy, and it is Us,” University of Chicago assistant professor Blase Polite showed data from several studies showing that patients older than 65 are typically half as likely to be offered an experimental cancer treatment. When elderly patients are offered the chance to enroll in a clinical trial, they are as likely - if not more so - as those under 65 to say Yes, he found.

The gap in enrolling elderly patients in clinical trial may stem from a larger problem of physician-patient communication, many presenters argued. Decisions about cancer treatment are certainly different for a 45-year-old vs. a 75-year-old, and a patient’s weighing of treatment side effects, quality of life, and the chance of a cure may change with age. But as Northwestern’s Linda Emanuel argued, physicians need to better understand that internal calculus for elderly patients facing the possibility of death.

“[There are] gratifications that are unique to those that are facing the end of life, through age or through cancer or through other terminal conditions,” Emanuel said. “What is that kind of wellbeing? I don’t think we know, we in the research field. We don’t have measures for it and we don’t have methods for it.”

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Loneliness is bad for your health. The work of John Cacioppo and others has proven this connection repeatedly over the last decade, finding links between loneliness and blood pressure, sleep quality, dementia, gene expression, and many other medical measures. The evidence has built to the point that loneliness could be considered a serious risk factor for poor health, joining more established factors such as obesity or smoking.

But for those risk factors, there are established treatments. These may not be easy for patients, but there are methods supported by science to help a person stop smoking or reduce their weight, thereby decreasing their risk of disease. However, the correct strategy for reducing a person’s loneliness is not so obvious. Is it simply a matter of surrounding a lonely person with people, giving them more opportunities to socialize? Do they need help developing social skills? Or does a lonely person need a sort of cognitive tune-up, a realignment to break out of the cycle of negative social thoughts and perceptions?

“If we know that loneliness is involved in health problems, the next question is what can we do to mitigate it,” Cacioppo, a professor of psychology at the University of Chicago, said.

Looking to build a better intervention for loneliness, Cacioppo teamed up with Christopher Masi, assistant professor of medicine at the University of Chicago Medical Center, for what’s called a meta-analysis, a wide review of the existing body of research on reducing loneliness. Essentially, the researchers looked at every study published between 1970 and 2009 that tested an intervention designed to directly target loneliness. The search brought in studies of all different types and sizes, and much of the work involved finding a way to boil their diverse study designs and results into numbers that would allow for comparison.

“Over the years there have been some qualitative reviews, not looking at the numbers quantitatively, but getting a gestalt for what seems to work and what doesn’t seem to work,” Masi said. “We thought that while that’s helpful, a quantitative meta-analysis would be more helpful and more reliable.”

In social science as well as medicine, not all studies are created equal. Some interventions were tried on a single group, with the amount of loneliness assessed before and after the treatment. Others compared a group receiving an intervention to a control group. But the gold standard was studies which compared randomized groups, minimizing any sample biases that could distort results.

Though there were only 20 such studies amidst the hundreds that the researchers uncovered, pooling their results yielded interesting findings. Previous qualitative meta-analyses concluded that group interventions were more effective than one-on-one interventions, but crunching the numbers revealed no difference between the two. Yet when all the studies were combined, the average effect on loneliness was significant, providing evidence that loneliness is indeed sensitive to treatment.

“We rigorously focused on the best studies and we still found a significant effect,” Masi said.

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A great deal of attention has been paid in recent years to the issue of racial and ethnic health disparities. Statistic after statistic reveals that minorities in the United States, particularly African-American and Hispanic populations, are in poorer health on average compared to American whites. Infant mortality, heart disease, diabetes, obesity, cancer and other maladies appear in often shockingly higher rates in minority populations, reflecting differences frequently attributed to socioeconomic factors and access to quality health care. But a new study by University of Chicago Medical Center researchers finds that a major contributor to those disparities might be traced back to what’s in the medicine cabinet.

The National Social Life, Health, and Aging Project (NSHAP) is a research effort launched out of the University of Chicago to study a large sample of older Americans. In 2005 and 2006, more than 3,000 in-home interviews were conducted across the country with people between the ages of 57 and 85 about their social activity, their health, and their medical care. As part of the interview, researchers not only asked the subject what medications they were currently taking, they looked at the drugs with their own eyes, taking a medication inventory “by direct observation.”

That thorough scan allowed Dima Qato, Caleb Alexander, and colleagues to analyze racial and ethnic patterns of medication use with unprecedented high fidelity. Previous studies which used insurance claims or prescriptions written to measure medication usage missed a key human factor, said Alexander, assistant professor of medicine.

“As we all know from own experience, what you are prescribed and what you take are often quite different,” Alexander said. “This data was unique in that it allowed for us to observe, from a nationally representative sample of individuals, the medicines people were actually taking.”

The analysis focused on medications prescribed to people at high risk for cardiovascular disease, a condition that has seen great progress recently in preventive medicine. Those included both the cholesterol-lowering prescription drug class of statins and the well-known over-the-counter drug aspirin, which is recommended to people at risk of heart attack and stroke for its anti-clotting abilities. Before the researchers even got to comparing different races and ethnicities, a disturbing overall trend appeared regarding use of these medicines.

“We found that across the board, regardless of race, there was evidence of under-use of both stains and aspirin,” said Qato, a research associate in the Department of Obstetrics & Gynecology.

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