A company uses AI to fight muscle loss and unhealthy aging
There’s a growing need to slow down the aging process. The world’s population is getting older and, according to one estimate, 80 million Americans will be 65 or older by 2040. As we age, the risk of many chronic diseases goes up, from cancer to heart disease to Alzheimer’s.
BioAge Labs, a company based in California, is using genetic data to help people stay healthy for longer. CEO Kristen Fortney was inspired by the genetics of people who live long lives and resist many age-related diseases. In 2015, she started BioAge to study them and develop drug therapies based on the company’s learnings.
The team works with special biobanks that have been collecting blood samples and health data from individuals for up to 45 years. Using artificial intelligence, BioAge is able to find the distinctive molecular features that distinguish those who have healthy longevity from those who don’t.
In December 2022, BioAge published findings on a drug that worked to prevent muscular atrophy, or the loss of muscle strength and mass, in older people. Much of the research on aging has been in worms and mice, but BioAge is focused on human data, Fortney says. “This boosts our chances of developing drugs that will be safe and effective in human patients.”
How it works
With assistance from AI, BioAge measures more than 100,000 molecules in each blood sample, looking at proteins, RNA and metabolites, or small molecules that are produced through chemical processes. The company uses many techniques to identify these molecules, some of which convert the molecules into charged atoms and then separating them according to their weight and charge. The resulting data is very complex, with many thousands of data points from patients being followed over the decades.
BioAge validates its targets by examining whether a pathway going awry is actually linked to the development of diseases, based on the company’s analysis of biobank health records and blood samples. The team uses AI and machine learning to identify these pathways, and the key proteins in the unhealthy pathways become their main drug targets. “The approach taken by BioAge is an excellent example of how we can harness the power of big data and advances in AI technology to identify new drugs and therapeutic targets,” says Lorna Harries, a professor of molecular genetics at the University of Exeter Medical School.
Martin Borch Jensen is the founder of Gordian Biotechnology, a company focused on using gene therapy to treat aging. He says BioAge’s use of AI allows them to speed up the process of finding promising drug candidates. However, it remains a challenge to separate pathologies from aspects of the natural aging process that aren’t necessarily bad. “Some of the changes are likely protective responses to things going wrong,” Jensen says. “Their data doesn’t…distinguish that so they’ll need to validate and be clever.”
Developing a drug for muscle loss
BioAge decided to focus on muscular atrophy because it affects many elderly people, making it difficult to perform everyday activities and increasing the risk of falls. Using the biobank samples, the team modeled different pathways that looked like they could improve muscle health. They found that people who had faster walking speeds, better grip strength and lived longer had higher levels of a protein called apelin.
Apelin is a peptide, or a small protein, that circulates in the blood. It is involved in the process by which exercise increases and preserves muscle mass. BioAge wondered if they could prevent muscular atrophy by increasing the amount of signaling in the apelin pathway. Instead of the long process of designing a drug, they decided to repurpose an existing drug made by another biotech company. This company, called Amgen, had explored the drug as a way to treat heart failure. It didn’t end up working for that purpose, but BioAge took note that the drug did seem to activate the apelin pathway.
BioAge tested its new, repurposed drug, BGE-105, and, in a phase 1 clinical trial, it protected subjects from getting muscular atrophy compared to a placebo group that didn’t receive the drug. Healthy volunteers over age 65 received infusions of the drug during 10 days spent in bed, as if they were on bed rest while recovering from an illness or injury; the elderly are especially vulnerable to muscle loss in this situation. The 11 people taking BGE-105 showed a 100 percent improvement in thigh circumference compared to 10 people taking the placebo. Ultrasound observations also revealed that the group taking the durg had enhanced muscle quality and a 73 percent increase in muscle thickness. One volunteer taking BGE-105 did have muscle loss compared to the the placebo group.
Heather Whitson, the director of the Duke University Centre for the study of aging and human development, says that, overall, the results are encouraging. “The clinical findings so far support the premise that AI can help us sort through enormous amounts of data and identify the most promising points for beneficial interventions.”
More studies are needed to find out which patients benefit the most and whether there are side effects. “I think further studies will answer more questions,” Whitson says, noting that BGE-105 was designed to enhance only one aspect of physiology associated with exercise, muscle strength. But exercise itself has many other benefits on mood, sleep, bones and glucose metabolism. “We don’t know whether BGE-105 will impact these other outcomes,” she says.
The future
BioAge is planning phase 2 trials for muscular atrophy in patients with obesity and those who have been hospitalized in an intensive care unit. Using the data from biobanks, they’ve also developed another drug, BGE-100, to treat chronic inflammation in the brain, a condition that can worsen with age and contributes to neurodegenerative diseases. The team is currently testing the drug in animals to assess its effects and find the right dose.
BioAge envisions that its drugs will have broader implications for health than treating any one specific disease. “Ultimately, we hope to pioneer a paradigm shift in healthcare, from treatment to prevention, by targeting the root causes of aging itself,” Fortney says. “We foresee a future where healthy longevity is within reach for all.”
A newly discovered brain cell may lead to better treatments for cognitive disorders
Swiss researchers have discovered a third type of brain cell that appears to be a hybrid of the two other primary types — and it could lead to new treatments for many brain disorders.
The challenge: Most of the cells in the brain are either neurons or glial cells. While neurons use electrical and chemical signals to send messages to one another across small gaps called synapses, glial cells exist to support and protect neurons.
Astrocytes are a type of glial cell found near synapses. This close proximity to the place where brain signals are sent and received has led researchers to suspect that astrocytes might play an active role in the transmission of information inside the brain — a.k.a. “neurotransmission” — but no one has been able to prove the theory.
A new brain cell: Researchers at the Wyss Center for Bio and Neuroengineering and the University of Lausanne believe they’ve definitively proven that some astrocytes do actively participate in neurotransmission, making them a sort of hybrid of neurons and glial cells.
According to the researchers, this third type of brain cell, which they call a “glutamatergic astrocyte,” could offer a way to treat Alzheimer’s, Parkinson’s, and other disorders of the nervous system.
“Its discovery opens up immense research prospects,” said study co-director Andrea Volterra.
The study: Neurotransmission starts with a neuron releasing a chemical called a neurotransmitter, so the first thing the researchers did in their study was look at whether astrocytes can release the main neurotransmitter used by neurons: glutamate.
By analyzing astrocytes taken from the brains of mice, they discovered that certain astrocytes in the brain’s hippocampus did include the “molecular machinery” needed to excrete glutamate. They found evidence of the same machinery when they looked at datasets of human glial cells.
Finally, to demonstrate that these hybrid cells are actually playing a role in brain signaling, the researchers suppressed their ability to secrete glutamate in the brains of mice. This caused the rodents to experience memory problems.
“Our next studies will explore the potential protective role of this type of cell against memory impairment in Alzheimer’s disease, as well as its role in other regions and pathologies than those explored here,” said Andrea Volterra, University of Lausanne.
But why? The researchers aren’t sure why the brain needs glutamatergic astrocytes when it already has neurons, but Volterra suspects the hybrid brain cells may help with the distribution of signals — a single astrocyte can be in contact with thousands of synapses.
“Often, we have neuronal information that needs to spread to larger ensembles, and neurons are not very good for the coordination of this,” researcher Ludovic Telley told New Scientist.
Looking ahead: More research is needed to see how the new brain cell functions in people, but the discovery that it plays a role in memory in mice suggests it might be a worthwhile target for Alzheimer’s disease treatments.
The researchers also found evidence during their study that the cell might play a role in brain circuits linked to seizures and voluntary movements, meaning it’s also a new lead in the hunt for better epilepsy and Parkinson’s treatments.
“Our next studies will explore the potential protective role of this type of cell against memory impairment in Alzheimer’s disease, as well as its role in other regions and pathologies than those explored here,” said Volterra.
Researchers claimed they built a breakthrough superconductor. Social media shot it down almost instantly.
Harsh Mathur was a graduate physics student at Yale University in late 1989 when faculty announced they had failed to replicate claims made by scientists at the University of Utah and the University of Wolverhampton in England.
Such work is routine. Replicating or attempting to replicate the contraptions, calculations and conclusions crafted by colleagues is foundational to the scientific method. But in this instance, Yale’s findings were reported globally.
“I had a ringside view, and it was crazy,” recalls Mathur, now a professor of physics at Case Western Reserve University in Ohio.
Yale’s findings drew so much attention because initial experiments by Stanley Pons of Utah and Martin Fleischmann of Wolverhampton led to a startling claim: They were able to fuse atoms at room temperature – a scientific El Dorado known as “cold fusion.”
Nuclear fusion powers the stars in the universe. However, star cores must be at least 23.4 million degrees Fahrenheit and under extraordinary pressure to achieve fusion. Pons and Fleischmann claimed they had created an almost limitless source of power achievable at any temperature.
Like fusion, superconductivity can only be achieved in mostly impractical circumstances.
But about six months after they made their startling announcement, the pair’s findings were discredited by researchers at Yale and the California Institute of Technology. It was one of the first instances of a major scientific debunking covered by mass media.
Some scholars say the media attention for cold fusion stemmed partly from a dazzling announcement made three years prior in 1986: Scientists had created the first “superconductor” – material that could transmit electrical current with little or no resistance. It drew global headlines – and whetted the public’s appetite for announcements of scientific breakthroughs that could cause economic transformations.
But like fusion, superconductivity can only be achieved in mostly impractical circumstances: It must operate either at temperatures of at least negative 100 degrees Fahrenheit, or under pressures of around 150,000 pounds per square inch. Superconductivity that functions in closer to a normal environment would cut energy costs dramatically while also opening infinite possibilities for computing, space travel and other applications.
In July, a group of South Korean scientists posted material claiming they had created an iron crystalline substance called LK-99 that could achieve superconductivity at slightly above room temperature and at ambient pressure. The group partners with the Quantum Energy Research Centre, a privately-held enterprise in Seoul, and their claims drew global headlines.
Their work was also debunked. But in the age of internet and social media, the process was compressed from half-a-year into days. And it did not require researchers at world-class universities.
One of the most compelling critiques came from Derrick VanGennep. Although he works in finance, he holds a Ph.D. in physics and held a postdoctoral position at Harvard. The South Korean researchers had posted a video of a nugget of LK-99 in what they claimed was the throes of the Meissner effect – an expulsion of the substance’s magnetic field that would cause it to levitate above a magnet. Unless Hollywood magic is involved, only superconducting material can hover in this manner.
That claim made VanGennep skeptical, particularly since LK-99’s levitation appeared unenthusiastic at best. In fact, a corner of the material still adhered to the magnet near its center. He thought the video demonstrated ferromagnetism – two magnets repulsing one another. He mixed powdered graphite with super glue, stuck iron filings to its surface and mimicked the behavior of LK-99 in his own video, which was posted alongside the researchers’ video.
VanGennep believes the boldness of the South Korean claim was what led to him and others in the scientific community questioning it so quickly.
“The swift replication attempts stemmed from the combination of the extreme claim, the fact that the synthesis for this material is very straightforward and fast, and the amount of attention that this story was getting on social media,” he says.
But practicing scientists were suspicious of the data as well. Michael Norman, director of the Argonne Quantum Institute at the Argonne National Laboratory just outside of Chicago, had doubts immediately.
Will this saga hurt or even affect the careers of the South Korean researchers? Possibly not, if the previous fusion example is any indication.
“It wasn’t a very polished paper,” Norman says of the Korean scientists’ work. That opinion was reinforced, he adds, when it turned out the paper had been posted online by one of the researchers prior to seeking publication in a peer-reviewed journal. Although Norman and Mathur say that is routine with scientific research these days, Norman notes it was posted by one of the junior researchers over the doubts of two more senior scientists on the project.
Norman also raises doubts about the data reported. Among other issues, he observes that the samples created by the South Korean researchers contained traces of copper sulfide that could inadvertently amplify findings of conductivity.
The lack of the Meissner effect also caught Mathur’s attention. “Ferromagnets tend to be unstable when they levitate,” he says, adding that the video “just made me feel unconvinced. And it made me feel like they hadn't made a very good case for themselves.”
Will this saga hurt or even affect the careers of the South Korean researchers? Possibly not, if the previous fusion example is any indication. Despite being debunked, cold fusion claimants Pons and Fleischmann didn’t disappear. They moved their research to automaker Toyota’s IMRA laboratory in France, which along with the Japanese government spent tens of millions of dollars on their work before finally pulling the plug in 1998.
Fusion has since been created in laboratories, but being unable to reproduce the density of a star’s core would require excruciatingly high temperatures to achieve – about 160 million degrees Fahrenheit. A recently released Government Accountability Office report concludes practical fusion likely remains at least decades away.
However, like Pons and Fleischman, the South Korean researchers are not going anywhere. They claim that LK-99’s Meissner effect is being obscured by the fact the substance is both ferromagnetic and diamagnetic. They have filed for a patent in their country. But for now, those claims remain chimerical.
In the meantime, the consensus as to when a room temperature superconductor will be achieved is mixed. VenGennep – who studied the issue during his graduate and postgraduate work – puts the chance of creating such a superconductor by 2050 at perhaps 50-50. Mathur believes it could happen sooner, but adds that research on the topic has been going on for nearly a century, and that it has seen many plateaus.
“There's always this possibility that there's going to be something out there that we're going to discover unexpectedly,” Norman notes. The only certainty in this age of social media is that it will be put through the rigors of replication instantly.