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.”
Scientists turn pee into power in Uganda
At the edge of a dirt road flanked by trees and green mountains outside the town of Kisoro, Uganda, sits the concrete building that houses Sesame Girls School, where girls aged 11 to 19 can live, learn and, at least for a while, safely use a toilet. In many developing regions, toileting at night is especially dangerous for children. Without electrical power for lighting, kids may fall into the deep pits of the latrines through broken or unsteady floorboards. Girls are sometimes assaulted by men who hide in the dark.
For the Sesame School girls, though, bright LED lights, connected to tiny gadgets, chased the fears away. They got to use new, clean toilets lit by the power of their own pee. Some girls even used the light provided by the latrines to study.
Urine, whether animal or human, is more than waste. It’s a cheap and abundant resource. Each day across the globe, 8.1 billion humans make 4 billion gallons of pee. Cows, pigs, deer, elephants and other animals add more. By spending money to get rid of it, we waste a renewable resource that can serve more than one purpose. Microorganisms that feed on nutrients in urine can be used in a microbial fuel cell that generates electricity – or "pee power," as the Sesame girls called it.
Plus, urine contains water, phosphorus, potassium and nitrogen, the key ingredients plants need to grow and survive. Human urine could replace about 25 percent of current nitrogen and phosphorous fertilizers worldwide and could save water for gardens and crops. The average U.S. resident flushes a toilet bowl containing only pee and paper about six to seven times a day, which adds up to about 3,500 gallons of water down per year. Plus cows in the U.S. produce 231 gallons of the stuff each year.
Pee power
A conventional fuel cell uses chemical reactions to produce energy, as electrons move from one electrode to another to power a lightbulb or phone. Ioannis Ieropoulos, a professor and chair of Environmental Engineering at the University of Southampton in England, realized the same type of reaction could be used to make a fuel from microbes in pee.
Bacterial species like Shewanella oneidensis and Pseudomonas aeruginosa can consume carbon and other nutrients in urine and pop out electrons as a result of their digestion. In a microbial fuel cell, one electrode is covered in microbes, immersed in urine and kept away from oxygen. Another electrode is in contact with oxygen. When the microbes feed on nutrients, they produce the electrons that flow through the circuit from one electrod to another to combine with oxygen on the other side. As long as the microbes have fresh pee to chomp on, electrons keep flowing. And after the microbes are done with the pee, it can be used as fertilizer.
These microbes are easily found in wastewater treatment plants, ponds, lakes, rivers or soil. Keeping them alive is the easy part, says Ieropoulos. Once the cells start producing stable power, his group sequences the microbes and keeps using them.
Like many promising technologies, scaling these devices for mass consumption won’t be easy, says Kevin Orner, a civil engineering professor at West Virginia University. But it’s moving in the right direction. Ieropoulos’s device has shrunk from the size of about three packs of cards to a large glue stick. It looks and works much like a AAA battery and produce about the same power. By itself, the device can barely power a light bulb, but when stacked together, they can do much more—just like photovoltaic cells in solar panels. His lab has produced 1760 fuel cells stacked together, and with manufacturing support, there’s no theoretical ceiling, he says.
Although pure urine produces the most power, Ieropoulos’s devices also work with the mixed liquids of the wastewater treatment plants, so they can be retrofit into urban wastewater utilities.
This image shows how the pee-powered system works. Pee feeds bacteria in the stack of fuel cells (1), which give off electrons (2) stored in parallel cylindrical cells (3). These cells are connected to a voltage regulator (4), which smooths out the electrical signal to ensure consistent power to the LED strips lighting the toilet.
Courtesy Ioannis Ieropoulos
Key to the long-term success of any urine reclamation effort, says Orner, is avoiding what he calls “parachute engineering”—when well-meaning scientists solve a problem with novel tech and then abandon it. “The way around that is to have either the need come from the community or to have an organization in a community that is committed to seeing a project operate and maintained,” he says.
Success with urine reclamation also depends on the economy. “If energy prices are low, it may not make sense to recover energy,” says Orner. “But right now, fertilizer prices worldwide are generally pretty high, so it may make sense to recover fertilizer and nutrients.” There are obstacles, too, such as few incentives for builders to incorporate urine recycling into new construction. And any hiccups like leaks or waste seepage will cost builders money and reputation. Right now, Orner says, the risks are just too high.
Despite the challenges, Ieropoulos envisions a future in which urine is passed through microbial fuel cells at wastewater treatment plants, retrofitted septic tanks, and building basements, and is then delivered to businesses to use as agricultural fertilizers. Although pure urine produces the most power, Ieropoulos’s devices also work with the mixed liquids of the wastewater treatment plants, so they can be retrofitted into urban wastewater utilities where they can make electricity from the effluent. And unlike solar cells, which are a common target of theft in some areas, nobody wants to steal a bunch of pee.
When Ieropoulos’s team returned to wrap up their pilot project 18 months later, the school’s director begged them to leave the fuel cells in place—because they made a major difference in students’ lives. “We replaced it with a substantial photovoltaic panel,” says Ieropoulos, They couldn’t leave the units forever, he explained, because of intellectual property reasons—their funders worried about theft of both the technology and the idea. But the photovoltaic replacement could be stolen, too, leaving the girls in the dark.
The story repeated itself at another school, in Nairobi, Kenya, as well as in an informal settlement in Durban, South Africa. Each time, Ieropoulos vowed to return. Though the pandemic has delayed his promise, he is resolute about continuing his work—it is a moral and legal obligation. “We've made a commitment to ourselves and to the pupils,” he says. “That's why we need to go back.”
Urine as fertilizer
Modern day industrial systems perpetuate the broken cycle of nutrients. When plants grow, they use up nutrients the soil. We eat the plans and excrete some of the nutrients we pass them into rivers and oceans. As a result, farmers must keep fertilizing the fields while our waste keeps fertilizing the waterways, where the algae, overfertilized with nitrogen, phosphorous and other nutrients grows out of control, sucking up oxygen that other marine species need to live. Few global communities remain untouched by the related challenges this broken chain create: insufficient clean water, food, and energy, and too much human and animal waste.
The Rich Earth Institute in Vermont runs a community-wide urine nutrient recovery program, which collects urine from homes and businesses, transports it for processing, and then supplies it as fertilizer to local farms.
One solution to this broken cycle is reclaiming urine and returning it back to the land. The Rich Earth Institute in Vermont is one of several organizations around the world working to divert and save urine for agricultural use. “The urine produced by an adult in one day contains enough fertilizer to grow all the wheat in one loaf of bread,” states their website.
Notably, while urine is not entirely sterile, it tends to harbor fewer pathogens than feces. That’s largely because urine has less organic matter and therefore less food for pathogens to feed on, but also because the urinary tract and the bladder have built-in antimicrobial defenses that kill many germs. In fact, the Rich Earth Institute says it’s safe to put your own urine onto crops grown for home consumption. Nonetheless, you’ll want to dilute it first because pee usually has too much nitrogen and can cause “fertilizer burn” if applied straight without dilution. Other projects to turn urine into fertilizer are in progress in Niger, South Africa, Kenya, Ethiopia, Sweden, Switzerland, The Netherlands, Australia, and France.
Eleven years ago, the Institute started a program that collects urine from homes and businesses, transports it for processing, and then supplies it as fertilizer to local farms. By 2021, the program included 180 donors producing over 12,000 gallons of urine each year. This urine is helping to fertilize hay fields at four partnering farms. Orner, the West Virginia professor, sees it as a success story. “They've shown how you can do this right--implementing it at a community level scale."
The Friday Five covers five stories in research that you may have missed this week. There are plenty of controversies and troubling ethical issues in science – and we get into many of them in our online magazine – but this news roundup focuses on scientific creativity and progress to give you a therapeutic dose of inspiration headed into the weekend.
Here are the promising studies covered in this week's Friday Five, featuring interviews with Dr. David Spiegel, associate chair of psychiatry and behavioral sciences at Stanford, and Dr. Filip Swirski, professor of medicine and cardiology at the Icahn School of Medicine at Mount Sinai.
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Here are the promising studies covered in this week's Friday Five, featuring interviews with Dr. David Spiegel, associate chair of psychiatry and behavioral sciences at Stanford, and Dr. Filip Swirski, professor of medicine and cardiology at the Icahn School of Medicine at Mount Sinai.
- Breathing this way cuts down on anxiety*
- Could your fasting regimen make you sick?
- This type of job makes men more virile
- 3D printed hearts could save your life
- Yet another potential benefit of metformin
* This video with Dr. Andrew Huberman of Stanford shows exactly how to do the breathing practice.
This podcast originally aired on March 3, 2023.