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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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Jamie McCarthy/Getty Images for Bill & Melinda Gates Foundation
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Medicine
Bill Gates is Spending $100 Million to Find a Cure for Alzheimer's
Jamie McCarthy/Getty Images for Bill & Melinda Gates Foundation
Jamie McCarthy/Getty Images for Bill & Melinda Gates Foundation

Not everyone who's blessed with a long life will remember it. Individuals who live into their mid-80s have a nearly 50 percent chance of developing Alzheimer's, and scientists still haven't discovered any groundbreaking treatments for the neurodegenerative disease [PDF]. To pave the way for a cure, Microsoft co-founder and philanthropist Bill Gates has announced that he's donating $100 million to dementia research, according to Newsweek.

On his blog, Gates explained that Alzheimer's disease places a financial burden on both families and healthcare systems alike. "This is something that governments all over the world need to be thinking about," he wrote, "including in low- and middle-income countries where life expectancies are catching up to the global average and the number of people with dementia is on the rise."

Gates's interest in Alzheimer's is both pragmatic and personal. "This is something I know a lot about, because men in my family have suffered from Alzheimer’s," he said. "I know how awful it is to watch people you love struggle as the disease robs them of their mental capacity, and there is nothing you can do about it. It feels a lot like you're experiencing a gradual death of the person that you knew."

Experts still haven't figured out quite what causes Alzheimer's, how it progresses, and why certain people are more prone to it than others. Gates believes that important breakthroughs will occur if scientists can understand the condition's etiology (or cause), create better drugs, develop techniques for early detection and diagnosis, and make it easier for patients to enroll in clinical trials, he said.

Gates plans to donate $50 million to the Dementia Discovery Fund, a venture capital fund that supports Alzheimer's research and treatment developments. The rest will go to research startups, Reuters reports.

[h/t Newsweek]

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A New Analysis of Chopin's Heart Reveals the Cause of His Death

For years, experts and music lovers alike have speculated over what caused celebrated composer Frederic Chopin to die at the tragically young age of 39. Following a recent examination of his heart, Polish scientists have concluded that Chopin succumbed to tuberculosis, just as his death certificate states, according to The New York Times.

When Chopin died in 1849, his body was buried in Paris, where he had lived, while his heart was transported to his home city of Warsaw, Poland. Chopin—who appeared to have been ill with tuberculosis (TB)—was terrified of the prospect of being buried alive, and nostalgic for his national roots. He asked for his heart to be cut out, and his sister later smuggled it past foreign guards and into what is now Poland.

Preserved in alcohol—likely cognac—and stored in a crystal jar, Chopin's heart was laid to rest inside Holy Cross Church in Warsaw. (It was removed by the Germans in 1944 during the Warsaw Uprising, and later returned.) But rumors began to swirl, as the same doctor tasked with removing the heart had also conducted an autopsy on the composer's body, according to the BBC.

The physician's original notes have been lost, but it's said he concluded that Chopin had died not from TB but from "a disease not previously encountered." This triggered some scholars to theorize that Chopin had died from cystic fibrosis, or even a form of emphysema, as the sickly musician suffered from chronic respiratory issues. Another suspected condition was mitral stenosis, or a narrowing of the heart valves.

Adhering to the wishes of a living relative, the Polish church and government have refused to let scientists conduct genetic tests on Chopin's heart. But over the years, teams have periodically checked up on the organ to ensure it remains in good condition, including once in 1945.

In 2014, a group of Chopin enthusiasts—including Polish scientists, religious officials, and members of the Chopin Institute, which researches and promotes Chopin's legacy—were given the go-ahead to hold a clandestine evening meeting at Holy Cross Church. There, they removed Chopin's heart from its perch inside a stone pillar to inspect it for the first time in nearly 70 years.

Fearing the jar's alcohol would evaporate, the group added hot wax to its seal and took more than 1000 photos of its contents. Pictures of the surreptitious evening procedure weren't publicly released, but were shown to the AP, which described Chopin's preserved heart as "an enlarged white lump."

It's unclear what prompted a follow-up investigation on Chopin's heart, or who allowed it, but an early version of an article in the American Journal of Medicine states that experts—who did not open the jar—have newly observed that the famed organ is "massively enlarged and floppy," with lesions and a white, frosted appearance. These observations have prompted them to diagnose the musician's cause of death as pericarditis, which is an inflammation of tissue around the heart. This likely stemmed from his tuberculosis, they said.

Some scientists might still clamor at the prospect of testing tissue samples of Chopin's heart. But Michael Witt of the Polish Academy of Sciences—who was involved in this latest examination—told The Guardian that it was unnecessary to disturb what many consider to be a symbol of national pride.

"Some people still want to open it in order to take tissue samples to do DNA tests to support their ideas that Chopin had some kind of genetic condition," Witt said. "That would be absolutely wrong. It could destroy the heart, and in any case, I am quite sure we now know what killed Chopin."

[h/t The New York Times]

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