Testosterone May Protect Against Asthma

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Asthma, a disease of the lungs that causes inflammation, swelling, wheezing and shortness of breath, affects both sexes, but with one notable difference: Boys tend to grow out of asthma after puberty, and men are far less likely to develop it in adulthood than women are. Australian researchers explored the idea that testosterone may have a protective effect against asthma—and they believe it does, pinpointing some of the mechanisms by which it occurs. Their study results are published in the Journal of Experimental Medicine.

To understand testosterone’s effects, says co-lead author Gabrielle Belz, a professor of molecular immunology at the University of Melbourne, you must first understand a family of immune cells known as innate lymphoid cells, or ILC2s. These cells are found on various surfaces in the body: the lungs, gastrointestinal tract, and the skin, to name a few. “Their job is to sense what’s happening in the external environment and make adjustments based on that,” Belz tells Mental Floss. In asthma, these cells proliferate in high numbers and accumulate in the airways where they trigger chemicals, such as cytokines and leukocytes, “that promote that inflammatory response that results in the airways swelling [and] narrowing, and shortness of breath occurs,” she says.

Males have fewer of these cells than females, Belz says, “because the testosterone receptor regulates the generation of these cells.” Plus, the androgen receptors, whose job it is to sense testosterone, become activated in the presence of testosterone. This suppresses the generation of these ILC2 cells, though Belz and her team are still exploring the mechanism by which it does so. With fewer cells present, there are fewer pro-inflammatory signals—which explains why men are less likely to develop asthma.

To test these effects in mouse models, the researchers ran a number of different experiments, beginning with a baseline analysis of the tissues of healthy male and female mice. They found a significantly increased presence of ILC2s in female mice compared to males, specifically in the lungs of the female mice, where the frequencies and total numbers of ILC2s were “twofold higher” than in males.

In another experiment, the researchers tested the tissue of mice that had been genetically modified not to have the testosterone-sensing androgen receptors—essentially, these mice lacked the ability to suppress the ILC2 cells, making them more likely to have asthma symptoms. These mice showed ILC2 numbers comparable to female mice, as did castrated male mice. The castrated male mice “responded as intact females, indicating that endogenous male sex hormones act as critical regulators [of ILC2s],” the authors write in their paper.

They also took tissue from male and female mice that had been given ovalbumin-induced asthma, and found that there were higher numbers of inflammatory leukocytes in the female mice than in the males.

The mouse models suggest that testosterone is protective against asthma, so the next steps are to study human immune cells from blood samples in a dish. Scientists could expose the human cells to different mediators to stimulate the testosterone pathway. They can also implant the human cells into mouse models to get a more accurate understanding of how the human cells might function. “Our preclinical animal modes are surrogates for the situations that might occur in humans,” Belz says.

This is all well and good if you’re male, but if you’re female, or a prepubescent child, further research is needed to come up with a treatment for asthma. Hormones are crucial for the development and growth of the body, so they can’t simply give testosterone to women and children with asthma “because that could disrupt a whole heap of things in the body,” Belz says. What they hope to do next is to discover receptors in women and children that they can target, and to create synthetic molecules that function in the same way as testosterone—without the impact of a hormone.

If they can achieve a synthetic testosterone, they would ideally be able to formulate an inhaled drug that can be taken through an inhaler, similar to other drugs for lung-related diseases.

Delving into these kinds of differences in how the sexes respond to disease is part of a "big push in the field to have a personalized approach to medicine," says Belz. "So you’d have a slightly different approach to males or females to get on top of these diseases."

Archaeologists Uncover World's Oldest Known Brewery in Israel

People have been knocking back beers for 13,000 years, according to new archaeological findings out of the Middle East. As Science magazine reports, evidence of wheat and barley-based beer was found inside stone mortars carved into the floor of a cave near Haifa, Israel.

The Raqefet Cave was used as a burial site by the Natufians, a group of semi-nomadic hunter-gatherers who were also responsible for the world’s oldest known bread, which was discovered in Jordan in July. These findings challenge previous evidence that traced the origin of beer back just 5000 years.

Beer was also previously believed to be merely a by-product of bread-making, but archaeologists say that isn’t necessarily the case. Instead, researchers believe beer may been served during ritual feasts “to venerate the dead and/or to enhance group cohesion among the living,” researchers wrote in their paper, published in the Journal of Archaeological Science: Reports.

Remarkably, the Stanford University researchers who made this discovery weren't even looking for evidence of alcohol. “We did not set out to find alcohol in the stone mortars, but just wanted to investigate what plant foods people may have consumed because very little data was available in the archaeological record,” Li Liu, a professor of Chinese archaeology at Stanford, said in a statement.

Researchers theorize that beer brewing may have inspired the Natufians to cultivate cereals in the region, but it’s not currently known whether beer or bread came first. The mortars dug into the cave floor were reportedly used for storing and pounding wheat and barley, as well as brewing beer.

The beverage wasn’t exactly what we know as beer today, though. According to the BBC, the prehistoric beer was “gruel-like” and similar to porridge. It was likely weaker than modern beer, too.

[h/t Science]

Newly Uncovered Galileo Letter Details How He Tried to Avoid the Inquisition

Galileo Before The Papal Tribunal by Robert Henry. Hulton Archive, Getty Images
Galileo Before The Papal Tribunal by Robert Henry. Hulton Archive, Getty Images

Galileo Galilei was one of the Roman Catholic Inquisition’s most famous targets. As a result of his outspoken support for the theory that all the planets, Earth included, revolve around the Sun, the Catholic Church charged him with heresy and he spent the last years of his life under house arrest. Galileo was well aware that he was on the Church’s hit list, and a newly discovered letter shows that at one point, he tried to tone down his ideas to avoid persecution, according to Nature and Ars Technica.

The letter in question, written in 1613, solves a long-held mystery for Galileo scholars. It was found in the library of the Royal Society, where it has been for at least 250 years.

Galileo’s beef with the Catholic Church came about because of his support for heliocentrism—the idea that the solar system centers around the Sun—as advocated in Nicolaus Copernicus’s book De Revolutionibus. Galileo’s scientific writings clearly endorsed Copernicus’s theory of the world, including in personal correspondence that was widely disseminated, and in some cases, he directly questioned the scientific merit of Biblical passages.

In 1613, Galileo wrote to a friend and former student named Benedetto Castelli who was then teaching mathematics at the University of Pisa. The letter was a long treatise on Galileo’s thoughts on Copernicus’s ideas and religion, arguing that science and astronomy should not be overpowered by religious doctrin . (He would later expand this into his Letter to the Grand Duchess Christina.) As with many of Galileo’s writings at the time, the letter was copied and disseminated widely, and eventually, a friar named Niccolò Lorini forwarded it to the Inquisition in Rome in 1615.

This is where things get tricky. Galileo claimed that the version of the letter Lorini sent was doctored to be more inflammatory. He sent a less controversial version of the letter to a friend, saying that it was the original document and should be forwarded to the Vatican, essentially to clear his name. But scholars have never been able to be totally sure if he was telling the truth about the letter being doctored.

This newly discovered letter suggests that he was lying, and that he himself was looking to tone down his rhetoric to appease the Catholic Church and keep authorities from quashing the spread of heliocentric ideas. The original copy found in the Royal Society archives shows changes to the wording in what appears to be Galileo’s handwriting. The seven-page letter, signed “G.G.,” includes changes like swapping the word “false” for the more slippery “look different from the truth,” changing “concealing” to “veiling,” and other edits that seek to tone down the rhetoric that inflamed Church leaders. The wording and handwriting corresponds to similar writing by Galileo at the time. Based on this finding, it seems that Galileo did seek to make his ideas more palatable to the Catholic Church in the hopes of escaping persecution by the Inquisition.

Discovered on a research trip by science historian Salvatore Ricciardo of Italy's University of Bergamo, the letter may have been overlooked in the Royal Society archives because it was cataloged as being dated October 21, 1613 rather than the date it actually bears, December 21, 1613. However, it’s unclear how it came to the Royal Society in the first place. The document is the subject of a forthcoming article by Ricciardo and his colleagues in the Royal Society journal Notes and Records, according to Nature.

The minor changes Galileo made did not successfully hold off the Church’s crackdown on heliocentrism. In 1616, the Inquisition ordered Galileo to stop teaching or defending the theory, and several of his books were subsequently banned. He would stand trial again almost two decades later, in 1633, on suspicion of holding heretical thoughts. He was found guilty and sentenced to house arrest, where he remained until his death in 1642.

[h/t Ars Technica]

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