A Link Between Stress and Aging in African-Americans

A recent study finds that lifetime stress in a population of African Americans causes chemical changes to their DNA that may be associated with an increased risk of aging related diseases.

(Image: Rhonda Baer, National Cancer Institute)

(Image: Rhonda Baer, National Cancer Institute)

Using a previously established DNA-based predictor of age known as the “epigenetic clock,” researchers found that a cohort of highly-traumatized African Americans were more likely to show aging-associated biochemical signatures in their DNA’s epigenetic clock regions at an earlier age than what would otherwise be predicted by their chronological age.

These chemical alterations to DNA’s epigenetic clock were found to be a result of hormonal changes that occur during the body’s stress response and corresponded to genetic profiles associated with aging-related diseases.

The study was performed by researchers at the Max Planck Institute of Psychiatry in Germany, including Duke University adjunct faculty and psychiatrist Dr. Anthony S. Zannas. The findings were published in a recent issue of Genome Biology.

“Our genomes have likely not evolved to tolerate the constant pressure that comes with today’s fast-paced society,” says lead author Zannas.

Though it may come as no surprise that chronic stress is detrimental to human health, these findings provide a novel biological mechanism for the negative effects of cumulative lifetime stressors, such as those that can come with being a discriminated minority.

Epigenetics is the study of how environmental factors switch our genes on or off. The epigenetic clock is comprised of over 300 sites in our DNA that are subject to a certain chemical modification known as methylation, which physically prevents those sites from being expressed (i.e., turns them off). Conversely, areas within the epigenetic clock can also be de-methylated to turn genes on. Each methylation event can be thought of as a tick of the epigenetic clock’s metaphorical second-hand, corresponding to the passing of physiological time.

During times of stress, a family of hormones known as glucocorticoids becomes elevated throughout the body. These glucocorticoids cause the chemical addition or removal of methyl groups to areas of DNA that the authors found to be located in the same regions that comprise the epigenetic clock. What’s more, the specific changes in methylation were found to correspond with gene expression profiles associated with coronary artery disease, arteriosclerosis, and leukemias.

This link between stress, glucocorticoids, and the epigenetic clock provides evidence that lifetime stress experienced by highly traumatized African Americans promotes physiological changes that affect their overall health and longevity.

The authors make an important distinction between cumulative lifetime stress and current stress. A small number of instances of acute stress may result in a correspondingly small number of methylation changes in the epigenetic clock, but it is the cumulative methylation events from chronic stress that give rise to lasting physiological detriments.

Though the authors make no direct claims regarding the physiological effects of racial inequities prevalent in today’s society, the findings perhaps shed light on the health disparities observed between disadvantaged African American populations and more privileged demographics, including increased mortality rates for cancer, heart disease, and stroke.

KatyRiccione

Glucocorticoids become elevated during the body’s stress response and lead to changes in DNA methylation that promote the expression of genes associated with aging.
Illustration by Katy Riccione

Interestingly, the epigenetic effects of lifetime stress were blunted in individuals who underwent significant childhood trauma, suggesting that early trauma may trigger mechanisms of physiological resilience to chronic stress later in life. In other words, if racial minorities are more likely to face hardships during their upbringing, perhaps they are also better prepared to cope with the chronic stress that comes with, for instance, losing a job or ending a marriage.

Though the study relies on data from an African American cohort, Dr. Zannas believes that the same conclusions are likely applicable to other highly stressed populations: chronic stress leads to lasting changes in our epigenome that may increase our likelihood of aging-related diseases, while acute stress was not found to have any long-term epigenetic effects.

So a single tough calculus exam won’t shave years off of your life, but consistent 80-hour work weeks just may.

In a world where everyday stress is unavoidable, whether it be from the hardships faced as a minority or the demands of being a full-time student, what lifestyle choices can we make to limit the detriments to our health? Dr. Zannas emphasizes that the “solution is not to avoid all stressors, but to prevent excessive stressors when possible and to learn to live with unavoidable stress constructively.”

The study underscores the importance of stress management on our general well-being. Future research may highlight the direct chemical benefits to our epigenome that are afforded by mindfulness, psychotherapy, diet/exercise, and other modes of stress relief. “Learning to better cope with stress is the best way to reduce our physiological response to it and the resultant harmful effects.”

Katy_Riccione_100Guest Post by Katy Riccione, Ph.D. Candidate in Biomedical Engineering

One Small Worm, One Duke Senior, and One Big Conference

Duke senior Grace Lim isn’t grossed out by the innards of the tiny worm C. elegans. In fact, she finds them beautiful.

As a researcher in the David Sherwood Lab, she peers inside the transparent 1-millimeter creature under a microscope, watching for “cell invasion” — a process that occurs when one type of cell literally bursts into an area occupied by another type of cell.

Version 2

Grace Lim presenting the results of her research at the AAAS Annual Meeting on Saturday.

Last weekend, the aspiring developmental biologist had the opportunity to take her work to the national stage when she presented at the Student Poster Competition as part of the annual AAAS meeting in Washington, D.C.

“It’s been really exciting,” said Lim. “The researchers here are experts and it is great to learn about their projects. At the same time, I’ve met scientists from all different fields who have asked questions and provided insights that I didn’t expect.”

Cell invasion plays a key role in organism growth and development, Lim said. For example, a fertilized egg will use cell invasion to implant itself into the uterine wall. However, cell invasion can also occur in less desirable processes, like cancer and other diseases.

In her work, Lim created C. elegans mutants that lacked specific genes related to cell invasion. She then observed whether uterine cells in the growing mutants could still invade tissue in the vulva — a key milestone in the growth of the developing larva.

C. elegans is a good system to study because it is transparent, so you can watch these biological processes happening under a microscope,” she said.

C_elegans

The tiny transparent C. elegans. Photo courtesy of the National Human Genome Research Institute

Her experiments uncovered four new genes that appear to regulate cell invasion in C. elegans. In addition to presenting at the conference, Lim will also be writing up these results as an honors thesis.

Lim, who wants to pursue a graduate degree in biology after finishing up at Duke, says her favorite part of working in the Sherwood lab has been interacting with the graduate students. “We work together to come up with creative ways to solve problems, which is something you don’t always get to do in class,” she said.

And her favorite part of working with C. elegans?

“They have this amazing ability to control their metabolism,” she said. “We grow these worms in petri dishes, and when the plate fills up and they run of out food, they just stop growing. But if you take a few and put them on a new plate they grow again, as if nothing had happened.”

Post by Kara Manke

Kara J. Manke, PhD

A Dead Parrot? Not Yet. But It Could Sure Use Your Help

An international team of gene sequencing scientists, including some at Duke, want to sequence the genomes of all living kakapo — a critically endangered flightless parrot of New Zealand – while there are still 125 of them left in the world.

Kakapo (Strigops_habroptilus)

A one-year-old Kakapo named Pura on Codfish Island in 2005, by Mnolf, via Wikimedia Commons.

This is the first project aiming to sequence every member of a given species. The scientists and their collaborators are hoping the public can help through a crowd-funding effort. They hope to raise $45,000 US and are a little more than halfway there. With just 2 and a half months left, you can help write the end to this story.

Four years ago, Duke research specialist Jason Howard picked up a children’s book from the library to read to his 6-year-old daughter. It was about the kakapo (Strigops habroptilus), a flightless, nocturnal parrot that smells like honey.

Howard works in the Duke lab of neurobiologist Erich Jarvis, a Howard Hughes Medical Investigator who is co-leading a massive, ongoing effort to sequence the genomes of all 10,000 bird species. So, Howard’s library book pick was not exactly random. (In fact, he was sequencing the parakeet genome at the time.)

This sweet face belongs to Felix the Kakapo, photographed in 2006 by Brent Barrett (originally posted to Flikr - via Wikimedia Commons)

This sweet face belongs to Felix the Kakapo, photographed in 2006 by Brent Barrett (originally posted to Flikr – via Wikimedia Commons)

But as Howard read about efforts to save this beloved — and rapidly aging — bird population, he asked his daughter whether she thought he should make the kakapo’s genome a priority. (To which she said, “Yes, daddy, do it!”)

Howard was able to obtain a DNA sample from the kakapo, a feat in itself, and get a rough draft of the sequence. “But the sequencing technology [three years ago] wasn’t as good then and it was a lot more expensive,” he said.

He wanted to get a higher quality genome and study genomes of individuals, in part because there are so few kakapo left. Because this bird is among the most ancient species of parrot, it would also give Jarvis’s lab a better understanding of the evolution of vocal learning and speech imitation, where many of their studies focus.

Advances in genome sequencing even in the past year have already answered the group’s wish for a more-detailed kakapo genome. Jarvis’s lab completed the genome of a kakapo named Jane; their so-called ‘reference’ genome will allow them to more simply and inexpensively piece together the sequences of other individual kakapo. They just needed the funds to do more.

As luck would have it, molecular ecologist Bruce Robertson, an associate professor at the University of Otago, Andrew Digby of the New Zealand Department of Conservation and David Iorns of the Genetic Rescue Foundation approached Howard, while he was working on Jane’s genome, about funding and crowdsourcing a project to sequence all of the remaining kakapo. “I had never dreamed of doing all 125,” Howard said.

Jason Howard Duke

Jason Howard

Conservation efforts that started in the 1980s have already employed breeding strategies to boost dwindling population, but with individual genomes in hand, the group will be able to understand which kakapo harbor genetic susceptibility to specific diseases and to more effectively breed them to produce offspring with more robust immune systems. (One day, scientists might even be able to modify disease-vulnerable genes using gene-editing technology.) The genomes will also allow them to investigate any genetic causes of low fertility in these birds, which mate only intermittently.

Kakapo currently reside in the wild on just two of New Zealand’s small islands, because human-introduced predators, including cats and dogs, ran them off the mainland.

Kakapo Recovery has access to museum samples of deceased birds from areas where they are now extinct, including some from nearly 200 years ago. If the project is well-funded, they can tap into these museum specimens to get a better understanding of the various island populations and possible clues about their demise.

As of February 15, the team’s crowdfunding effort has reached more than 150 backers, but they would like to see more make a donation. To learn more about kakapo, check out Kakapo Recovery and Genetic Rescue Foundation.

Please stick around and watch a male Kakapo named Scirocco acting inappropriately as Stephen Fry narrates. (BBC-TV)

 

KellyRae_Chi_100Post by Kelly Rae Chi

Pace of Aging Story Makes Top Ten

A study led by Center for Child and Family faculty fellows Daniel Belsky and Terrie Moffitt  which found that some people grow old significantly faster than others, was named the No. 4 news story of 2015 by Science News.

The paper, published the week of July 6 in the Proceedings of the National Academy of Sciences, compared a panel of 18 biological measures that may be combined to determine whether people are aging faster or slower than their peers.

Dan Belsky

Dan Belsky

The data comes from the Dunedin Study, a landmark longitudinal study that has tracked more than a thousand people born in the same town between 1972-73. Health measures like blood pressure and liver function have been taken regularly, along with interviews and other assessments.

“We set out to measure aging in these relatively young people,” said first author Belsky, an assistant professor in the Department of Medicine. “Most studies of aging look at seniors, but if we want to be able to prevent age-related disease, we’re going to have to start studying aging in young people.”

Belsky said the progress of aging shows in human organs just as it does in eyes, joints and hair, but sooner. So, as part of their regular reassessment of the study population at age 38 in 2011, the team measured the functions of kidneys, liver, lungs, metabolic and immune systems. They also measured HDL cholesterol, cardiorespiratory fitness and the length of the telomeres—protective caps at the end of chromosomes that have been found to shorten with age.

Based on a subset of these biomarkers, the research team set a “biological age” for each participant, which ranged from under 30 to nearly 60 in the 38-year-olds.

According to Science News, “The finding tapped into a mystery that has long captivated scientists and the public alike…”

Read more about it on Duke Today.

CFP Logo headerGuest Post from the Center for Child and Family Policy

Iridescent Beauty: Development, function and evolution of plant nanostructures that influence animal behavior

Iridescent wings of a Morpho butterfly

Iridescent wings of a Morpho butterfly

Creatures like the Morpho butterfly on the leaf above appear to be covered in shimmering blue and green metallic colors. This phenomenon is called “iridescence,” meaning that color appears to change as the angle changes, much like soap bubbles and sea shells.

Iridescent behavior of a soap bubble

Iridescent behavior of a soap bubble

In animals, the physical mechanisms and function of structural color have been studied significantly as a signal for recognition or mate choice.

On the other hand, Beverley Glover believes that such shimmering in plants can actually influence animal behavior by attracting pollinators better than their non-iridescent counterparts. Glover,Director of Cambridge University Botanic Garden,  presented her study during the Biology Seminar Series in the French Family Science Center on Monday earlier this week.

Hibiscus Trionum

Hibiscus Trionum

The metallic property of flowers like the Hibiscus Trionum above are generated by diffraction grating – similar to the way CD shines – to create color from transparent material.

In order to observe the effects of the iridescence on pollinators like bees, Glover created artificial materials with a surface structure of nanoscale ridges, similar to the microscopic view of a petal’s epidermal surface below.

Nanoscale ridges on a petal's epidermal surface.

Nanoscale ridges on a petal’s epidermal surface.

In the first set of experiments, Glover and her team marked bees with paint to follow their behavior as they set the insects to explore iridescent flowers. Some were covered in a red grating – containing a sweet solution as a reward – and others with a blue iridescent grating – containing a sour solution as deterrent. The experiment demonstrated that the bees were able to detect the iridescent signal produced by the petal’s nanoridges, and – as a result – correctly identified the rewarding flowers.

Bees pollinating iridescent "flowers"

Bees pollinating iridescent “flowers”

With the evidence that the bees were able to see iridescence, Glover set out for the second experiment: once the bees find a specific type of flower, how long does it take them to find the same flower in a different location? Using the triangular arrangement of shimmering surfaces as shown below, Glover observed that iridescence produced by a diffraction grating leads to significant increase in foraging speed as compared to non-iridescent flowers.

Triangular formation of iridescent disks used for experimentation on bees

Triangular formation of iridescent disks used for experimentation on bees

While iridescence in plants is difficult to spot by a casual stroll through the garden, pollinators such as bees definitely can see it, and scientists have recently realized that insect vision and flower colors have co-evolved.

In order to ensure that pollen is transferred between flowers of the same species, these flowers have developed a unique structure of iridescence. As scientists work on understanding which plants produce these beautiful colors and how the nanoscale structure is passed down through reproduction, we can only look at our gardens in wonder at the vast amount of nature that still remains to be explored and learned.

Wonder of nature

Wonders of nature in an everyday garden

 

 

Beverley Glover is the Director of Cambridge University Botanic Garden and is currently accepting applications for PhD students

 

 

 

 

 

Post written by Anika Radiya-Dixit

 

Pinpointing the Cause of Coughs and Sneezes

Duke students are trying to help doctors find a faster way to pinpoint the cause of their patients’ coughs, sore throats and sniffles.

The goal is to better determine if and when to give antibiotics in order to stem the rise of drug-resistant superbugs, said senior Kelsey Sumner.

For ten weeks this summer, Sumner and fellow Duke student Christopher Hong teamed up with researchers at Duke Medicine to identify blood markers that could be used to tell whether what’s making someone sick is a bacteria, or a virus.

More than half of children who go to the doctor for a sore throat, ear infection, bronchitis or other respiratory illness leave with a prescription for antibiotics, even though the majority of these infections — more than 70% — turn out to be caused by viruses, which antibiotics can’t kill.

The end result is that antibiotics are prescribed roughly twice as often as they should be, to the tune of 11.4 million unnecessary prescriptions a year.

“It’s a big problem,” said Emily Ray Ko, MD, PhD, a physician at Duke Regional Hospital who worked with Sumner and Hong on the project, alongside biostatistician Ashlee Valente and infectious disease researcher Ephraim Tsalik of Duke’s Center for Applied Genomics and Precision Medicine.

Prescribing antibiotics when they aren’t needed can make other infections trickier to treat.

Fast, accurate genetic tests may soon help doctors tell if you really need antibiotics. Photo from the Centers for Disease Control and Prevention.

Fast, accurate genetic tests may soon help doctors tell if you really need antibiotics. Photo from the Centers for Disease Control and Prevention.

That’s because antibiotics wipe out susceptible bacteria, but a few bacteria that are naturally resistant to the drugs survive, which allows them to multiply without other bacteria to keep them in check.

More than two million people develop drug-resistant bacterial infections each year.

A single superbug known as methicillin-resistant Staphylococcus aureus, or MRSA, kills more Americans every year than emphysema, HIV/ AIDS, Parkinson’s disease and homicide combined.

Using antibiotics only when necessary can help, Ko said, but doctors need a quick and easy test that can be performed while the patient is still in the clinic or the emergency room.

“Most doctors need to know within an hour or two whether someone should get antibiotics or not,” Ko said. “Delaying treatment in someone with a bacterial infection could have serious and potentially life threatening consequences, which is one of the main reasons why antibiotics are over-prescribed.”

With help from Sumner and Hong, the team has identified differences in patients’ bloodwork they hope could eventually be detected within a few hours, whereas current tests can take days.

The researchers made use of the fact that bacteria and viruses trigger different responses in the immune system.

They focused on the genetic signature generated by tiny snippets of genetic material called microRNAs, or miRNAs, which play a role in controlling the activity of other genes within the cell.

Using blood samples from 31 people, ten with bacterial pneumonia and 21 with flu virus, they used a technique called RNA sequencing to compare miRNA levels in bacterial versus viral infections.

So far, the researchers have identified several snippets of miRNA that differ between bacterial and viral infections, and could be used to discriminate between the two.

“Hopefully it could be used for a blood test,” Sumner said.

“One goal of these types of assays could be to identify infections before symptoms even appear,” Ko said. “Think early detection of viral infections like Ebola, for example, where it would be helpful to screen people so you know who to quarantine.”

Sumner and Hong were among 40 students selected for a summer research program at Duke called Data+. They presented their work at the Data+ Final Symposium on July 23 in Gross Hall.

Data+ is sponsored by the Information Initiative at Duke, the Social Sciences Research Institute and Bass Connections. Additional funding was provided by the National Science Foundation via a grant to the departments of mathematics and statistical science.

RobinSmith_hed100

 

Writing by Robin Smith; photos and video by Christine Delp and Hannah McCracken