The week’s most astounding developments from the neobiological frontier.

July 29, 2021

Vascular theory of aging demonstrated in mice

Blood vessels are involved in many age-related diseases—from atherosclerosis to tumor metastasis to age-related macular degeneration. At the center of it all is a signaling protein known as vascular endothelial growth factor (VEGF), which promotes the formation of new blood vessels and is the target of existing drugs like the anti-VEGF antibody bevacizumab (Avastin), often prescribed for cancer treatment. But researchers at Hebrew University of Jerusalem demonstrated that VEGF may play a much more fundamental role in aging by showing its loss was associated with several hallmarks of aging in mice, including inflammaging, and that treating mice with VEGF helps them live healthier, longer. Could the same approach prevent aging in humans? Science

A magnetic device for deadly brain cancer

Glioblastoma is an aggressive, malignant, hard-to-treat, and deadly form of brain cancer—fewer than half of all people diagnosed with it survive more than a year. There are lots of treatments (including Avastin), and one type of adjuvant therapy involves wearing a cap that emits electromagnetic fields, disrupting tumor cell growth. A team of doctors at Houston Methodist University in Texas has developed a similar approach, designing a cap that emits oscillating magnetic waves, the safety of which they successfully tested on one person with an inoperable tumor last year. The device was promising, and there is radiological evidence it shrank the tumor, but it’s not yet clear whether the device will work. Tragically, the patient suffered a fall, which cut short their treatment after 36 days, and died from the cancer soon after. Frontiers in Oncology

When is a death not a death? When it’s not reported, apparently

Once a medical device is approved by the U.S. Food and Drug Administration, post-market safety surveillance requires that any adverse events—malfunctions, injuries, deaths, or “other”—must be reported to the FDA’s Manufacturer and User Facility Device Experience (MAUDE) database. The FDA is required by law to investigate any death linked to a medical device, but they do not routinely investigate other adverse events. A study from the University of California, San Francisco this week reveals that a significant number of people who died between 1991 and 2020 had their deaths “miscategorized.” Of 291,141 reported adverse events, 23 percent were “missed” deaths classified as other adverse events. It’s not clear what accounts for the discrepancy or whether device manufacturers are gaming the system, but the authors say more accurate reporting would enhance patient safety. JAMA Internal Medicine

Genome editing slows progression of familial Alzheimer’s in mice

Brain-wide genome editing may be a viable approach to treating familial Alzheimer’s, which accounts for about a quarter of all cases, and other “monogenic” diseases tied to a single gene. That’s the conclusion of a promising new study by Hong Kong University of Science and Technology researchers who used CRISPR to edit the genomes of transgenic mice carrying a form of the human APP gene, which is linked to familial Alzheimer’s. Given a CRISPR/adenovirus vector designed to cross the blood–brain barrier and target the APP gene, the mice were spared disease pathology and cognitive decline for at least six months after a single injection. Nature Biomedical Engineering

Circadian rhythms may help us avoid food poisoning

How do eating patterns affect immunity? Informed by a recent study in mice, our bodies may kickstart protective innate immunity ahead of feeding, following a circadian pattern of expression—a possible mammalian evolutionary adaptation shared by humans that mitigates the risk of exposure to contaminated foods. Researchers at the University of Texas Southwestern Medical Center found that mice prepare for potentially microbe-laced meals by inducing innate immune cells in the gut to secrete large amounts of antimicrobial proteins like STAT3, a rhythmic expression that follows a classic circadian rhythm of day-night variation. They found that the mice were more resistant to Salmonella typhimurium infections around mealtimes than while sleeping. Chronic sleep disruption in people is linked with increased risk for infection and altered eating patterns—could this be part of the reason why? Cell

Whole brain connectome of rhesus monkey

Scientists at the University of Science and Technology of China are reporting a 1-micrometer whole-brain “connectome” of the rhesus macaque. Uncovering the mammalian connectome is hugely challenging because axonal connections are too small to be resolved with techniques like MRI. Instead, high-resolution microscopy of individual brain slices must be meticulously stacked, a very time-consuming undertaking for an animal like a macaque, whose 6-7 billion neurons may each make thousands of connections to other cells. The Chinese team overcame these challenges using a technique they developed called semi-automated reconstruction and tracing (SMART), which allowed them to map the entire monkey brain in under 100 hours. Nature Biotechnology

On our watchlist: War of the Worlds, pandemic edition

Science fiction fans have long credited H.G. Wells for the timeless genius of The War of the Worlds, the serialized novel he first published for American audiences in Cosmopolitan magazine in 1897. The story has inspired numerous adaptations, including the infamous panic-inducing radio broadcast by Orson Welles in 1938, the big-budget Tom Cruise vehicle a few years ago, and many musicals, plays, and television series in between. The latest and perhaps the best of all is the French–British TV series of the same name starring Gabriel Byrne (The Usual Suspects) and Daisy Edgar-Jones (Normal People), which wraps its second season this Sunday at 9pm. The COVID-19 pandemic has given the show’s dystopian visions of urban apocalypse new relevance, and its theme of laboratory-engineered viruses with gain-of-function mutations makes it eerily timely. Epix