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Mitochondria May Be the Missing Link in Understanding Stress Response

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Scientists have long looked to anatomy and neurology to understand and ameliorate stress responses in humans. Now, a pioneering study, recently published in Proceedings of the National Academy of Sciences, suggests that mitochondria—the tiny energy centers inside our cells, which convert food into ATP, the crucial molecule that stores the energy humans need to do pretty much everything—may play a more significant role in the stress responses of mammals than previously understood, and even in understanding psychiatric and neurologic diseases.

The study was headed by Douglas Wallace, director of the Center for Mitochondrial and Epigenomic Medicine at The Children’s Hospital of Philadelphia and a leading researcher in the genetics of mitochondria for 40 years. He is among the first to prove that defects in energy metabolism can cause disease.

Wallace and his team found that even slight changes in mitochondrial genes had a large effect on how mammals respond to stress in their environments. Wallace’s team bred mice with different genetic mutations to their mitochondrial DNA (mtDNA). “With these mutants in hand we could expose them to a mild environmental stress, such as 30 minutes in confinement,” Wallace tells mental_floss.

They then measured the neuroendocrine, inflammatory, metabolic, and gene transcription systems, which are the systems most effected by stress. “We found the changes in mitochondrian response had a markedly different response from normal mitochondria,” he says.

They mixed two normal, but different, mtDNAs in mice to prevent maternal inheritance of the mtDNA. This resulted in “hyperexcitable mice with severe learning and memory defects,” according to a press statement

Because humans and mice share a similar degree of variation in their mtDNA, Wallace suspects that the mouse results “might have a comparable effect” in human DNA.

While research is conflicting about how much stress increases risk of disease, psychiatrists have a term for the common physiological decline that happens when people are under continuous stress: allostatic load. “What is the connection between stress and declining bodily functions?" Wallace says. "The intermediate is the mitochondria.”

Wallace believes that the bioenergetics of mitochondrial function is the overlooked piece in understanding everything from psychiatric and neurologic diseases to aging, partly a result of the current “anatomical paradigm” in the scientific community, which focuses mostly on nuclear DNA, anatomy, and neurology. “What’s missed is the realization that mitochondria is much more important than just making ATP," he says. "It has a central regulatory role, because nothing in your body can go forward without energy. Mitochondria is the missing link between human behavior and human physiology.”

For example, he points out that neurons are “extraordinarily energetically demanding,” and that certain diseases could actually be a mitochondria disease. “All the tissues affected in common diseases also have the highest mitochondria energy demand, and it’s hard to see any anatomical difference between a normal and affected patient, because you can’t see energy,” he says. Wallace makes the case that aging could be chalked up to being “fundamentally the decline of the mitochondria’s ability to produce the energy to power the cells to keep us at optimum health.”

Wallace’s colleague Peter Burke has developed a new technique that makes it possible to analyze the energy of a single mitochondrion. “So now we can understand how subtle changes can have big effects on energy production and physiology,” Wallace says.

Wallace believes that further study could reveal ways to observe and even stop changes in the mitochondria before the obvious symptoms of disease have even begun—and that further research will show that changes in these “energetic genes” will be important in understanding diseases. But he’s concerned that the current scientific paradigm will be slow to embrace it, and thus fund it. He hopes it gets much more research, because he believes it could lead to a whole new generation of neuropsychiatric therapeutics: “This study will lead to a revolution in neuroscience," he says. "Whether the neuroscientists will accept it is another question."

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Emery Smith
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Stones, Bones, and Wrecks
The 'Alien' Mummy Is of Course Human—And Yet, Still Unusual
Emery Smith
Emery Smith

Ata has never been an alien, but she's always been an enigma. Discovered in 2003 in a leather pouch near an abandoned mining town in Chile's Atacama Desert, the tiny, 6-inch mummy's unusual features—including a narrow, sloped head, angled eyes, missing ribs, and oddly dense bones—had both the “It's aliens!” crowd and paleopathologists intrigued. Now, a team of researchers from Stanford University School of Medicine and UC-San Francisco has completed a deep genomic analysis that reveals why Ata looks as she does.

As they lay out in a paper published this week in Genome Research, the researchers found a host of genetic mutations that doomed the fetus—some of which have never been seen before.

Stanford professor of microbiology and immunology Garry Nolan first analyzed Ata back in 2012; the mummy had been purchased by a Spanish businessman and studied by a doctor named Steven Greer, who made her a star of his UFO/ET conspiracy movie Sirius. Nolan was also given a sample of her bone marrow; his DNA analysis confirmed she was, of course, human. But Nolan's study, published in the journal Science, also found something very odd: Though she was just 6 inches long when she died—a typical size for a midterm fetus—her bones appeared to be 6 to 8 years old. This did not lead Nolan to hypothesize an alien origin for Ata, but to infer that she may have had a rare bone disorder.

The current analysis confirmed that interpretation. The researchers found 40 mutations in several genes that govern bone development; these mutations have been linked to "diseases of small stature, rib anomalies, cranial malformations, premature joint fusion, and osteochondrodysplasia (also known as skeletal dysplasia)," they write. The latter is commonly known as dwarfism. Some of these mutations are linked to conditions including Ehlers-Danlos syndrome, which affects connective tissue, and Kabuki syndrome, which causes a range of physical deformities and cognitive issues. Other mutations known to cause disease had never before been associated with bone growth or developmental disorders until being discovered in Ata.

scientist measures the the 6-inch-long mummy called Ata, which is not an alien
Emery Smith

"Given the size of the specimen and the severity of the mutations … it seems likely the specimen was a pre-term birth," they write. "While we can only speculate as to the cause for multiple mutations in Ata's genome, the specimen was found in La Noria, one of the Atacama Desert's many abandoned nitrate mining towns, which suggests a possible role for prenatal nitrate exposure leading to DNA damage."

Though the researchers haven't identified the exact age of Ata's remains, they're estimated to be less than 500 years old (and potentially as young as 40 years old). Genomic analysis also confirms that Ata is very much not only an Earthling, but a local; her DNA is a nearest match to three individuals from the Chilote people of Chile.

In a press statement, study co-lead Atul Butte, director of the Institute for Computational Health Sciences at UC-San Francisco, stressed the potential applications of the study to genetic disorders. "For me, what really came of this study was the idea that we shouldn't stop investigating when we find one gene that might explain a symptom. It could be multiple things going wrong, and it's worth getting a full explanation, especially as we head closer and closer to gene therapy," Butte said. "We could presumably one day fix some of these disorders."

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Health
Just Two Cans of Soda a Day May Double Your Risk of Death From Heart Disease
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iStock

If you've been stocking your refrigerator full of carbonated corn syrup in anticipation of warmer weather, the American Heart Association has some bad news. The advocacy group on Wednesday released results of research that demonstrate a link between consumption of sugary drinks—including soda, fruit juices, and other sweetened beverages—and an increased risk of dying from heart disease.

Study participants who reported consuming 24 ounces or more of sugary drinks per day had twice the risk of death from coronary artery disease of those who averaged less than 1 ounce daily. There was also an increased risk of death overall, including from other cardiovascular conditions.

The study, led by Emory University professor Jean Welsh, examined data taken from a longitudinal study of 17,930 adults over the age of 45 with no previous history of heart disease, stroke, or diabetes. Researchers followed participants for six years, and examined death records to determine causes. They observed a greater risk of death associated with sugary drinks even when they controlled for other factors, including race, income, education, smoking habits, and physical activity. The study does not show cause and effect, the researchers said, but does illuminate a trend.

The study also noted that while it showed an increased risk of death from heart disease, consumption of sugary foods was not shown to carry similar risk. One possible explanation is that the body metabolizes the sugars differently: Solid foods carry other nutrients, like fat and protein, that slow metabolism, while sugary drinks provide an undiluted influx of carbohydrates that the body must process.

The news will likely prove troublesome for the beverage industry, which has long contended with concerns that sugary drinks contribute to type 2 diabetes and tooth decay. Some cities, including Seattle, have introduced controversial "soda tax" plans that raise the sales tax on the drinks in an effort to discourage consumption.

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