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

August 17, 2023

Breakthrough in young blood: It’s the platelets, bro!

“Heterochronic parabiosis” began as a bizarre mouse experiment at Berkeley: Surgically join the circulatory systems of young and old mice, and the old mice gained new life and improved cognitive function. It later became a sick joke about the excesses of Silicon Valley—older tech bros sucking the blood of younger techies in a bid to beat back aging. Even so, scientists marveled at its longevity potential and wondered how it works. Now researchers at University of California, San Francisco are reporting a potential answer. By spinning down blood plasma from the young mice to separate out its components and then injecting those fractions into older mice, they discovered that the rejuvenating element of the young blood is platelets—those tiny cell-like disks circulating by the millions in our blood stream to help us clot when we bleed. One protein in particular was the key component: chemokine platelet factor 4 (abbreviated PF4 and sometimes CXCL4). Its administration lowered age-related brain inflammation and improved cognition in older mice. Another protein, called CXCR3, was also seen to play a key role in this process—all of which suggests potential drug targets for reducing neuroinflammation and rescuing cognition as we age. Nature

Could this be an actual biomarker and drug target for chronic fatigue?

Chronic fatigue syndrome (also known as myalgic encephalomyelitis) is a debilitating and hard to diagnose condition marked by brain fog, muscle pain, sleeplessness, exercise intolerance, and excessive recovery times for any type of physical exertion. It’s a long-term condition, but what makes it particularly infuriating is its opaqueness. We don’t know what causes chronic fatigue—perhaps a virus, a bacterium, some environmental toxin, or all of the above. There are no biomarkers for definitively diagnosing it. Nor are there specific treatments or cures. You can seek psychotherapy, take meds for the pain or to help you sleep, or adapt your daily routines to get the most out of your faint energy. But now researchers at the National Heart, Lung, and Blood Institute in Bethesda, Maryland, are reporting a potential underlying mechanism. From the blood of a 38-year-old woman suffering from chronic fatigue, they identified an obscure human protein called Wiskott-Aldrich syndrome protein family member 3 (WASF3). In mouse studies, they showed that WASF3 levels inside muscle cells increase in response to stress, gravitate to the energy-producing mitochondria in cells, disrupt their normal function, and lower endurance. They showed that alleviating that stress decreases WASF3 levels and restores normal mitochondrial function, meaning that WASF3 could potentially be a target for treating chronic fatigue. PNAS

Potential gene therapy for alcoholism

Gene therapy could prevent people seeking treatment for alcoholism from falling off the wagon, according to researchers at Ohio State University who have tested the potential of this approach with eight male rhesus macaques. Technically known as alcohol use disorder, alcoholism affects more than 10 percent of U.S. adults and is linked to some 140,000 American deaths every year. Marked by changes to the brain’s mesolimbic reward pathways, alcoholism alters how dopamine is released in the brain, inducing a chemical dependency. But those brain changes can be altered through gene therapy, the researchers showed. Specifically, they inserted the gene for human glial-derived neurotrophic factor (hGDNF) directly into cells in the brain’s ventral tegmental area. That corrected dopamine changes in the mesolimbic reward pathway caused by chronic alcohol use. “Our findings suggest that this treatment can prevent relapse without requiring long-term treatment adherence by patients,” the authors say in a press statement. Nature Medicine

Revisiting the 14-day rule for embryos—again!

Human embryo research is controversial because it relies on… human embryos. For the last 40 years, such research has been legally constrained by an international convention called the 14-day rule. After two weeks, our central nervous systems begin to form and ethical concerns like Do embryos feel pain? led to the widely adopted ban. But lots of interesting things relevant for human health happen after day 15—like the entire critical developmental stage known as gastrulation. So almost everything we know about gastrulation comes from studies on mice or cell culture, which is one of the things that prompted experts last year to call for relaxing the 14-day rule, replacing it with a 28-day rule. The situation is further complicated by embryonic studies involving induced pluripotent stem cells. A new perspective this week calls for rethinking the legal definition of an embryo. Rather than number of days, base it on developmental ‘‘tipping points’’ instead, they recommend. Cell

Brain biomarkers of nicotine addiction

Researchers at Fudan University in Shanghai and Cambridge University in England have discovered a possible brain biomarker for nicotine addiction. Looking at brain images, cigarette smoking habits, and other behavioral data of 2,000 young adults when they were 14, 19, and 23, they identified an association between reduced volume of gray matter in the part of the brain known as the left ventromedial prefrontal cortex (vmPFC) and smoking initiation—possibly tied to increased propensity for rule breaking behavior enhanced by this anatomical distinction. A similar relationship between gray matter volume in the right vmPFC appears to be associated with the maintenance of smoking due to increased hedonistic reward mechanisms that sustain addictive behaviors. What this all means, they say, is that the gray matter volume in these brain regions could be biomarkers of smoking initiation and addiction, which could possibly lead to better early prevention and treatment approaches. Nature Communications

Hinge proteins—and why you should love them

Proteins that change their 3D conformation when coming into contact with their lock-and-key target are a basic feature of all molecular life. And if you could make designer 3D proteins that shape-shift the way you want, it could throw the door open on a whole new generation of nanoscale molecular detectors and a wide variety of lifesaving and lucrative applications. But therein lies the rub. Designing them from scratch is incredibly hard. But now those amazingly prolific researchers in David Baker’s lab at the University of Washington in Seattle used AI to design “hinge proteins” that feature stimulus-response disulfide latches that can controllably lock them in two different states. Science

Researchers at the University of Washington used AI to create proteins that toggle between two different shapes. Ian C Haydon/UW Institute for Protein Design

Do people need God when they have AI?

Researchers at the University of Chicago’s Booth School of Business and nearby Northwestern University’s Kellogg School of Management have demonstrated that exposure to robots and AI can explain religious declines across cultures and within countries, communities, and organizations—regardless of a person’s wealth, political beliefs, knowledge of science, or exposure to other types of tech. They explain this by observing that people tend to have exaggerated views of automation, thinking it allows them to break laws of nature and solve intractable, unsolvable problems—challenges once reserved for God or supernatural agents. Beliefs in such a profound AI-enhanced superhuman agency consequently erodes their belief in the divine. “Our findings show that the rise of AI and robotics has been a crucial and overlooked mechanism for explaining religious declines,” they write, predicting that the rise of automation could accelerate secularization in the 21st century. PNAS