A new method developed by MIT researchers can accelerate a privacy-preserving artificial intelligence training method by about 81 percent. This advance could enable a wider array of resource-constrained edge devices, like sensors and smartwatches, to deploy more accurate AI models while keeping user data secure.

The MIT researchers boosted the efficiency of a technique known as federated learning, which involves a network of connected devices that work together to train a shared AI model.

In federated learning, the model is broadcast from a central server to wireless devices. Each device trains the model using its local data and then transfers model updates back to the server. Data are kept secure because they remain on each device.

But not all devices in the network have enough capacity, computational capability, and connectivity to store, train, and transfer the model back and forth with the server in a timely manner. This causes delays that worsen training performance.

The MIT researchers developed a technique to overcome these memory constraints and communication bottlenecks. Their method is designed to handle a heterogenous network of wireless devices with varied limitations.

This new approach could make it more feasible for AI models to be used in high-stakes applications with strict security and privacy standards, like health care and finance.

“This work is about bringing AI to small devices where it is not currently possible to run these kinds of powerful models. We carry these devices around with us in our daily lives. We need AI to be able to run on these devices, not just on giant servers and GPUs, and this work is an important step toward enabling that,” says Irene Tenison, an electrical engineering and computer science (EECS) graduate student and lead author of a paper on this technique.

Her co-authors include Anna Murphy ’25, a machine-learning engineer at Lincoln Laboratory; Charles Beauville, a visiting student from Ecole Polytechnique Fédérale de Lausanne (EPFL) in Switzerland and a machine-learning engineer at Flower Labs; and senior author Lalana Kagal, a principal research scientist in the Computer Science and Artificial Intelligence Laboratory (CSAIL) at MIT. The research will be presented at the IEEE International Joint Conference on Neural Networks. 

Reducing lag time

Many federated learning approaches assume all devices in the network have enough memory to train the full AI model, and stable connectivity to transmit updates back to the server quickly.

But these assumptions fall short with a network of heterogenous devices, like smartwatches, wireless sensors, and mobile phones. These edge devices have limited memory and computational power, and often face intermittent network connectivity.

The central server usually waits to receive model updates from all devices, then averages them to complete the training round. This process repeats until training is complete.

“This lag time can slow down the training procedure or even cause it to fail,” Tenison says.

To overcome these limitations, the MIT researchers developed a new framework called FTTE (Federated Tiny Training Engine) that reduces the memory and communication overhead needed by each mobile device.

Their framework involves three main innovations.

First, rather than broadcasting the entire model to all devices, FTTE sends a smaller subset of model parameters instead, reducing the memory requirement for each device. Parameters are internal variables the model adjusts during training.

FTTE uses a special search procedure to identify parameters that will maximize the model’s accuracy while staying within a certain memory budget. That limit is set based on the most memory-constrained device.

Second, the server updates the model using an asynchronous approach. Rather than waiting for responses from all devices, the server accumulates incoming updates until it reaches a fixed capacity, then proceeds with the training round.

Third, the server weights updates from each device based on when it received them. In this way, older updates don’t contribute as much to the training process. These outdated data can hold the model back, slowing the training process and reducing accuracy.

“We use this semi-asynchronous approach because want to involve the least powerful devices in the training process so they can contribute their data to the model, but we don’t want the more powerful devices in the network to stay idle for a long time and waste resources,” Tenison says.

Achieving acceleration

The researchers tested their framework in simulations with hundreds of heterogeneous devices and a variety of models and datasets. On average, FTTE enabled the training procedure to reach completing 81 percent faster than standard federated learning approaches.

Their method reduced the on-device memory overhead by 80 percent and the communication payload by 69 percent, while attaining near the accuracy of other techniques.

“Because we want the model to train as fast as possible to save the battery life of these resource-constrained devices, we do have a tradeoff in accuracy. But a small drop in accuracy could be acceptable in some applications, especially since our method performs so much faster,” she says.

FTTE also demonstrated effective scalability and delivered higher performance gains for larger groups of devices.

In addition to these simulations, the researchers tested FTTE on a small network of real devices with varying computational capabilities.

“Not everyone has the latest Apple iPhone. In many developing countries, for instance, users might have less powerful mobile phones. With our technique, we can bring the benefits of federated learning to these settings,” she says.

In the future, the researchers want to study how their method could be used to increase the personalized performance of AI models on each device, rather than focusing on the average performance of the model. They also want to conduct larger experiments on real hardware.

This work was funded, in part, by a Takeda PhD Fellowship.

Nature Climate Change, Published online: 29 April 2026; doi:10.1038/s41558-026-02627-8

Droughts and tropical cyclones are two well-known hazards that can interact in dynamic ways. Now, research shows that rainfall from tropical cyclones shortens and weakens droughts in coastal regions but not in a uniform way.

Nature Climate Change, Published online: 29 April 2026; doi:10.1038/s41558-026-02625-w

Food security remains a major global challenge, which is only amplified by ongoing climate change. Here, I look back on a 2015 paper on climate change impacts on wheat and discuss subsequent research on agriculture and food security.

If you want to overthrow Big Tech, you’ll need Section 230. The paradigm shift being built with the Open Social Web can put communities back in control of social media infrastructure, and finally end our dependency on enshitified corporate giants. But while these incumbents can overcome multimillion-dollar lawsuits, the small host revolution could be picked off one by one without the protections offered by 230.

The internet as we know it is built on Section 230, a law from the 90s that generally says internet users are legally responsible for their own speech — not the services hosting their speech. The purpose of 230 was to enable diverse forums for speech online, which defined the early internet. These scattered online communities have since been largely captured by a handful of multi-billion dollar companies that found profit in controlling your voice online. While critics are rightly concerned about this new corporate influence and surveillance, some look to diminishing Section 230 as the nuclear option to regain control. 

The thing is, that would be a huge gift to Big Tech, and detrimental to our best shot at actually undermining corporate and state control of speech online. 

Dethroning Big Tech

We’re fed up with legacy social media trapping us in walled gardens, where the world's biggest companies like Google and Meta call the shots. Our communities, and our voices, are being held hostage as billionaires’ platforms surveil, betray, and censor us. We’re not alone in this frustration, and fortunately, people are collaborating globally to build another way forward: the Open Social Web. 

This new infrastructure puts the public’s interest first by reclaiming the principles of interoperability and decentralization from the early internet. In short, it puts protocols over platforms and lets people own their connections with others. Whether you choose a Fediverse app like Mastodon or an ATmosphere app like Bluesky, your audience and community stay within reach. It’s a vision of social media akin to our lives offline: you decide who to be in touch with and how, and no central authority can threaten to snuff out those connections. It’s social media for humans, not advertisers and authoritarians.

Behind that vision is a beautiful mess of protocols bringing the open social media web to life. Each protocol is a unique language for applications, determining how and where messages are sent. While this means there is great variety to these projects, it also means everyone who spins up a server, develops an app, or otherwise hosts others’ speech has skin in the game when it comes to defending Section 230.

What exactly is Section 230?

Section 230 protects freedom of expression online by protecting US intermediaries that make the internet work. Passed in 1996 to preserve the new bubbling communities online, 230 enshrined important protections for free expression and the ability to block or filter speech you don’t want on your site. One portion is credited as the “26 words that created the internet”:

“No provider or user of an interactive computer service shall be treated as the publisher or speaker of any information provided by another information content provider.” 

In other words, this bipartisan law recognizes that speech online relies on intermediaries — services that deliver messages between users — and holding them potentially liable for any message they deliver would only stifle that speech. Intuitively, when harmful speech occurs, the speaker should be the one held accountable. The effect is that most civil suits against users and services based on others' speech can quickly be dismissed, avoiding the most expensive parts of civil litigation. 

Section 230 was never a license to host anything online, however. It does not protect companies that create illegal or harmful content. Nor does Section 230 protect companies from intellectual property claims. 

What Section 230 has enabled, however, is the freedom and flexibility for online communities to self-organize. Without the specter of one bad actor exposing the host(s) to serious legal threats, intermediaries can moderate how they see fit or even defer to volunteers within these communities.

Why the Open Social Web Needs Section 230

The superpower of decentralized systems like the Fediverse is the ability for thousands of small hosts to each shoulder some of the burdens of hosting. No single site can assert itself as a necessary intermediary for everyone; instead, all must collaborate to ensure messages reach the intended audience. The result is something superior to any one design or mandate. It is an ecosystem that is greater than the sum of its parts, resilient to disruptions, and free to experiment with different approaches to community governance.

The open social web’s kryptonite though, is the liability participants can face as intermediaries. The greater the potential liability, the more interference from powerful interests in the form of legal threats, more monetary costs, and less space for nuance in moderation. And in practice, participants may simply stop hosting to avoid those risks. The end result is only the biggest and most resourced options can survive.

This isn’t just about the hosts in the Open Social Web, like Mastodon instances or Bluesky PDSes. In the U.S., Section 230’s protections extend to internet users when they distribute another person’s speech. For example, Section 230 protects a user who forwards an email with a defamatory statement. On the open social web, that means when you pass along a message to others through sharing, boosting, and quoting, you’re not liable for the other user’s speech. The alternative would be a web where one misclick could open you up to a defamation lawsuit.

Section 230 also applies to the infrastructure stack, too, like Internet service providers, content delivery networks, domain, and hosting providers. Protections even extend to the new experimental infrastructures of decentralized mesh networks.

Beyond the existential risks to the feasibility of indie decentralized projects in the United States, weakening 230 protections would also make services worse. Being able to customize your social media experience from highly curated to totally laissez-faire in the open social web is only possible when the law allows space for private experiments in moderation approaches. The algorithmically driven firehose forced on users by antiquated social media giants is driven by the financial interests of advertisers, and would only be more tightly controlled in a post-230 world.

Defending 230

Laws aimed at changing 230 protections put decentralized projects like the open social web in a uniquely precarious position. That is why we urge lawmakers to take careful consideration of these impacts. It is also why the proponents and builders of a better web must be vigilant defenders of the legal tools that make their work possible. 

The open social web embodies what we are protecting with Section 230. It’s our best chance at building a truly democratic public interest internet, where communities are in control.

Under a microscope, a bouquet of lollipop-like structures, each smaller than a grain of sand, waves gently in a petri dish of liquid. Suddenly, they snap together, like the jaws of a Venus flytrap, as a scientist waves a small magnet over the dish. What was previously an assemblage of tiny passive structures has transformed instantly into an active robotic gripper.

The lollipop gripper is one demonstration of a new type of soft magnetic hydrogel developed by engineers at MIT and their collaborators at the École Polytechnique Fédérale de Lausanne (EPFL) in Switzerland and the University of Cincinnati. In a study appearing today in the journal Matter, the MIT team reports on a new method to print and fabricate the gel, which can be made into complex, magnetically activated three-dimensional structures.

The new gel could be the basis for soft, microscopic, magnetically responsive robots and materials. Such magno-bots could be used in medicine, for instance to release drugs or grab biopsies when directed by an external magnet.

Making objects move with magnets is nothing new, at least at the macroscale. We can, for example, wave a refrigerator magnet over a pile of paper clips that will trail the magnet in response. And at the microscale, scientists have designed a variety of magnetic “micro-swimmers” — components that are smaller than a millimeter and can be directed remotely by a magnet to squeeze through small spaces. For the most part, these designs work by mixing magnetic particles into a printable resin and pulling the entire swimmer in the direction of an external magnet.

In contrast, the MIT team’s new material can be made into even more complex and deformable structures with micron-scale precision. These features could enable a magnetic millibot to move individual features and perform more complex maneuvers.

“We can now make a soft, intricate 3D architecture with components that can move and deform in complex ways within the same microscopic structure,” says study author Carlos Portela, the Robert N. Noyce Career Development Associate Professor of Mechanical Engineering at MIT. “For soft microscopic robotics, or stimuli-responsive matter, that could be a game-changing capability.”

The study’s MIT co-authors include graduate students Rachel Sun and Andrew Chen, along with Yiming Ji and Daryl Yee of EPFL and Eric Stewart of the University of Cincinnati.

In a flash

At MIT, Portela’s group develops new metamaterials — materials engineered with unique, microscopic architectures that give rise to beyond-normal material properties. Portela has fabricated a variety of such metamaterials, including extremely tough and stretchy architectures and designs that can manipulate sound and withstand violent impacts.

Most recently, he’s expanded his research to “programmable” materials, which can be engineered to change their properties in response to stimuli, such as certain chemicals, light, and electric and magnetic fields.

From the team’s perspective, magnetic stimuli stand out from the rest.

“With a magnetically responsive material, we have control at a distance and the response is instantaneous,” says co-lead author Andrew Chen. “We don’t have to wait for a slow chemical reaction or physical process, and we can manipulate the material without touching it.”

For the new study, the team aimed to create a magnetically responsive metamaterial that can be made into structures smaller than a millimeter. Researchers typically fabricate microstructures by using two-photon lithography — a high-resolution 3D printing technique that flashes a laser into a small pool of resin. With repeated flashes, the laser traces a microscopic pattern into the resin, which solidifies into the same pattern, ultimately creating a tiny, three-dimensional structure, layer by layer.

While 3D resin printing produces intricate microstructures, using the same process to print magnetic structures has been a challenge. Researchers have tried to combine the resin with magnetic nanoparticles before printing the mixture. But magnetic particles are essentially bits of metal that inherently scatter light away or agglomerate and sediment unintentionally. Scientists have found that any magnetic particles in the resin can reduce the laser’s power at a given spot and weaken the resulting structure or prevent its printing altogether.

“Directly 3D printing deformable micron-scale structures with a high fraction of magnetic particles is extremely difficult, often involving a tradeoff between magnetic functionality and structural integrity,” says Sun, a co-lead author on the work.

A printed double-dip

The researchers created a new way to fabricate magnetic microstructures, by combining 3D resin printing with a double-dip process. The researchers first applied conventional resin printing to create a microstructure using a typical polymer gel, with no added magnetic particles. Then they dipped the printed gel into a solution containing iron ions, which the gel can absorb. The iron-soaked structure is then dipped again in a second solution of hydroxide ions. The iron ions in the gel bond with the hydroxide ions, creating iron-oxide nanoparticles that are inherently magnetic.

With this new process, the team can print intricate structures smaller than a millimeter, and add magnetic properties to the structures after printing. What’s more, they are able to control how magnetic a structure’s individual features can be. They found that, by tuning the laser’s power as they print certain features, they can set how cross-linked, or “tight” the gel is when printed. The tighter the gel, the fewer magnetic particles it can form. In this way, the researchers can determine how magnetic each tiny feature can be.

“This provides unprecedented design freedom to print multifunctional structures and materials at the microscale,” Sun says.

As a demonstration, the team fabricated ball-and-stick structures resembling tiny lollipops. The structures were less than a millimeter in height, with balls that were smaller than a grain of sand. The researchers printed the lollipops out of polymer gel and infused each ball with different amounts of magnetic particles, giving them various degrees of magnetism. Under a microscope, they observed that when they passed an ordinary refrigerator magnet over the structures, the lollipops pulled toward the magnet in various degrees, in a configuration that mimicked gripping fingers.

“You could imagine a magnetic architecture like this could act as a small robot that you could guide through the body with an external magnet, and it could latch onto something, for instance to take a biopsy,” Portela says. “That is a vision that others can take from this work.”

The team also fabricated a magnetically responsive, “bistable” switch. They first printed a small millimeter-long rectangle of polymer gel and attached to either side four tiny, oar-like magnetic structures. Each oar measured about 8 microns thick — about the size of a red blood cell. When the team applied a magnet on one end of the rectangle, the oars flipped toward the magnet, pulling the rectangle in the same direction and locking it in that position. When the magnet was applied to the other side, the oars flipped again, pulling the rectangle, like a switch, in the opposite direction.

“We think this is a new kind of bistable mechanism that could be used, for instance, in a microfluidic device, as a magnetic valve to open or shut some flow,” Portela says. “For now, we’ve figured out how to fabricate magnetic complex architectures at the microscale and also spatially tune their properties. That opens up a lot of interesting ideas for soft miniature robots going forward.”

This research was supported, in part, by the National Science Foundation and the MathWorks seed grant program.

This work was performed, in part, in the MIT.nano fabrication and characterization facilities.

Two weeks ago, Anthropic announced that its new model, Claude Mythos Preview, can autonomously find and weaponize software vulnerabilities, turning them into working exploits without expert guidance. These were vulnerabilities in key software like operating systems and internet infrastructure that thousands of software developers working on those systems failed to find. This capability will have major security implications, compromising the devices and services we use every day. As a result, Anthropic is not releasing the model to the general public, but instead to a ...

President Donald Trump's jawboning of the markets is sending the wrong signals to oil producers by keeping crude prices artificially low.

Colombia's environment minister opens up about the country's effort to sidestep the U.N.'s slow-moving climate process.

A state judge found that the courts can't dictate energy policy.

The EPA administrator was quick to spar on a variety of fronts, including chemicals, climate change and the administration’s drive to deregulate.

The state activated a pair of 20-year power contracts for the country's first major offshore wind farm.

The Legislature last year eliminated a 2030 deadline to cut emissions. Environmentalists say the move opened the door for the state to soft-pedal its clean energy ambitions.

Gov. Kathy Hochul and legislative leaders continue to discuss weakening deadlines in the state’s 2019 climate law.

Behind the headline growth is a big shift, with investors moving away from riskier early-stage bets toward infrastructure supporting commercially viable technologies.

A new investigation claims Italian tanneries owned by LVMH are seeking exemptions to EU deforestation law while importing hides linked to Paraguayan forest loss.

Chad’s deputy prime minister said another 10 people were wounded in Saturday’s clashes in Igote village in Wadi Fira province near the Sudan border.

Climate change is widely believed to be having an effect on tick numbers: Ticks like warm, humid weather, and more can be seen after a mild winter.

Nature Climate Change, Published online: 28 April 2026; doi:10.1038/s41558-026-02624-x

Integrating knowledge across climate risks, societal responses and their interactions is a critical yet persistently challenging goal. We argue that advanced artificial intelligence frameworks, specifically foundation models, offer a new opportunity to unify these domains and support climate decision-making.

Robotically assembled building blocks could be a more environmentally friendly method for erecting large-scale structures than some existing construction techniques, according to a new study by MIT researchers.

The team conducted a feasibility study to evaluate the efficiency of constructing a simple building using “voxels,” which are modular 3D subunits that assemble into complex, durable structures.

After studying the performance of multiple voxels, the researchers developed three new designs intended to streamline building construction. They also produced a robotic assembler and a user-friendly interface for generating voxel-based building layouts and feeding instructions to the robots.

Their results indicate this voxel-based robotic assembly system could reduce embodied carbon — all of the carbon emitted during the lifecycle of building materials — by as much as 82 percent, compared with popular techniques like 3D concrete printing, precast modular concrete, and steel framing. The system would also be competitive in terms of cost and construction time. However, the choice of materials used to manufacture the voxels does play a major role in their carbon footprint and cost.

While scalability, durability, long-term robustness, and important considerations like fire resistance remain to be explored before such a system could be widely deployed, the researchers say these initial results highlight the potential of this approach for automated, on-site construction.

“I’m particularly excited about how the robotic assembly of discrete lattices can enable a practical way to apply digital fabrication to the built environment in a way that can let us build much more efficiently and sustainably,” says Miana Smith, a graduate student in the Center for Bits and Atoms (CBA) at MIT and lead author the study.

She is joined on the paper by Paul Richard, a graduate student at École Polytechnique Fédérale de Lausanne in Switzerland and former visiting researcher at MIT; Alfonso Parra Rubio, a CBA graduate student; and senior author Neil Gershenfeld, an MIT professor and the director of the CBA. The research appears in Automation in Construction.

Designing better building blocks

Over the past several years, researchers in the Center for Bits and Atoms have been developing voxels, which are lattice-structured building blocks that can be assembled into objects with high strength and stiffness, like airplane wings, wind turbine blades, and space structures.

“Here, we are taking aerospace principles and applying them to buildings. Why don’t we make buildings as efficiently as we make airplanes?” Gershenfeld says, based on prior work his lab has done on voxel assembly with NASA, Airbus, and Boeing.

To explore the feasibility of voxel-based assembly strategies for buildings, the researchers first evaluated the mechanical performance and sustainability of eight existing voxel designs, including a cuboctahedron made from glass-reinforced nylon and a Kelvin lattice made from steel.

Based on those evaluations, they developed a set of three voxels using a new geometry that could be more easily assembled robotically into a larger structure. The new design, based on a high-strength and high-stiffness octet lattice, mechanically self-aligns into rigid structures.

“The interlocking nature of these voxels means we can get nice mechanical properties without needing to have a lot of connectors in the system, so the construction process can run a lot faster,” Smith says.

To accelerate construction, they designed a robotic assembly system based on inchworm-like robots that crawl across a voxel structure by anchoring and extending their bodies. These Modular Inchworm Lattice Assembler robots, or MILAbots, use grippers on each end to place voxel building blocks and engage the snap-fit connections.

“The robots can assemble the voxels by dropping them into place and then stepping on them to have the pieces interlock. We can do precise maneuvers based on the mechanical relationship between the robots and the voxels,” Smith explains.

The team studied the embodied carbon needed to fabricate their new voxel designs using three materials: plastic, plywood, and steel. Then they evaluated the throughput and cost of using the robotic assembly system to build a simple, one-story building. The researchers compared these estimates with the performance of other construction methods.

Potential environmental benefits

They found that most existing voxels, and especially those made from plastics, performed poorly compared to existing methods in terms of sustainability, but the steel and wood voxels they designed offered significant environmental benefits.

For instance, utilizing their steel voxels would generate only 36 percent of the embodied carbon required for 3D concrete printing and 52 percent of the embodied carbon of precast concrete. The plywood voxels had the lowest carbon footprint, requiring about 17 percent and 24 percent of the embodied carbon needed, respectively.

“There is still a potential viable option for a plastics-based voxel approach, we just have to be a bit more strategic about which types of plastics, infills, and geometries we use,” Smith says.

In addition, projected on-site assembly time for the steel and wood voxel approaches averaged 99 hours, whereas existing construction methods averaged 155 hours.

These speed benefits rely on the distributed nature of voxel-based assembly. While one MILAbot working alone is far slower than existing techniques, with a team of 20 robots working in parallel, the system catches up to or surpasses existing automation methods at a lower cost.

“One benefit of this method is how incremental it is. You can start building, and if it turns out you need a new room, you can just add onto the structure. It is also reversible, so if your use changes, you can dissemble the voxels and change the structure,” Gershenfeld says.

The researchers also developed an interface that enables users to input or hand-design a voxelized structure. The automatic system determines the paths the MILAbots should follow for construction and sends commands to the assemblers.

The next step in this project will be a larger testbed in Bhutan, using the “super fab lab” that CBA helped set up there to replicate the robots to test construction for a planned sustainable city, Gershenfeld says.

Additional areas of future work include studying the stability of voxel structures under lateral loads, improving the design tool to account for the physics of the system, enhancing the MILAbots, and evaluating voxels that have integrated sheeting, insulation, or electrical and plumbing routing.

“Our work helps support why doing this type of distributed robot assembly might be a practical way to bring digital fabrication into building construction,” Smith says.

“This is yet another visionary example from Neil Gershenfeld and his team, of finding ways for buildings to build themselves with the help of tiny robotic machines. I’m now fascinated by how we can harness an idea like this to make it more affordable to make the outsides of buildings more engaging and joyful,” says Thomas Heatherwick, founder of the design and architecture firm Heatherwick Studio, who was not involved with this research.

This work was funded, in part, by the MIT Center for Bits and Atoms Consortia.

Patterns of molecular activity in the blood may hold clues not only to how fit someone is, but also to the biological processes that support physical performance. Researchers at MIT, GE HealthCare, and the U.S. Military Academy at West Point have developed a computational model that links thousands of these molecular signals to fitness levels, revealing pathways that could inform future studies to improve fitness training and speed injury or disease recovery.

To develop their model, the researchers analyzed more than 50,000 biomarkers in 86 cadets at the U.S. Military Academy who were training for a military competition. Using these data, the researchers were able to identify molecular pathways that appear to contribute to higher levels of physical fitness.

“We had 50,000 measurements, and we wanted to get it down to about 100 where there’s some likelihood that the markers that we’re measuring are mechanistically linked to physical fitness. So, not just a statistical correlation, of which there will be many, but markers where there’s a likelihood that there is a causal relationship,” says Ernest Fraenkel, the Grover M. Hermann Professor in Health Sciences and Technology in MIT’s Department of Biological Engineering.

These biomarkers can be measured by analyzing blood samples, which could offer a simple way to provide an athlete, for example, or perhaps someone with chronic illness or a long-term injury, with additional information about potential areas to focus their efforts to reduce risk of injury, accelerate recovery, or improve their performance ceiling beyond what conventional measures show.

Azar Alizadeh, a principal scientist with GE HealthCare’s Healthcare Technology and Innovation Center, is the paper’s lead author. Fraenkel and Luca Marinelli, a senior principal scientist with GE HealthCare, are the senior authors of the new study, which appears in the journal Communications Biology.

Mapping fitness

To find the genetic basis of a simple trait such as height, scientists can perform large-scale studies known as genome-wide association studies (GWAS), in which genetic markers from thousands of people can be linked with height. However, the picture becomes much more complicated for traits such as physical fitness, which is determined by the interplay of many different genetic, physiological, and environmental factors.

The researchers set out to try to identify some of those factors, working with a group of 86 volunteers at the U.S. Military Academy at West Point who were training for the Sandhurst Military Skills Competition. Alizadeh led the experimental study design and execution, in collaboration with GE HealthCare, GE Research, West Point, and MIT scientists. During the three-month study period, volunteers participated in up to five sessions. At each session, blood samples were taken before and after intense exercise. The researchers also measured other traits such as lean muscle mass and VO2 max (the maximum rate of oxygen consumption during exercise).

From the blood samples, the researchers were able to measure more than 50,000 biomarkers, which they obtained by analyzing DNA methylation patterns, sequencing messenger RNA transcripts, and analyzing thousands of the proteins and small molecules found in the samples.

From their set of 50,000 biomarkers, the researchers hoped to identify a smaller number that could predict overall physical fitness, as measured by performance on the Army Combat Fitness Test (ACFT). This test includes a 2-mile run, maximum deadlift (the heaviest weight a person can lift for a single repetition up to 340 pounds), and sprint-drag-carry, a test that involves sprinting, dragging a sled, and carrying kettlebells.

One way to do this would be to simply train a computational model to identify correlations between fitness and biomarkers. However, with only 86 subjects in the study, that approach would likely yield correlations that were random and did not actually contribute to physical fitness, Fraenkel says.

To take a more targeted approach, the researchers first created a network model that represents the interactions between the markers, based on existing databases that catalog those interactions. These connections might represent proteins that interact with each other in a signaling pathway, or a transcription factor that turns on a set of genes.

“We built a network that you can think of as a city map. You want to find the places in the city map that are lighting up — not just one light going on, but a whole bunch of houses or street lamps going on in the same neighborhood,” Fraenkel says. “We can find neighborhoods on this enormous molecular map that are active at the same time, in a way that correlates with the phenotype that we measure.”

“We built upon the network bioinformatics from the Fraenkel lab to create an end-to-end predictive modeling framework to discover biological expression circuits that drive groups of physical characteristics predictive of ACFT scores, for example, body composition or exercise physiology metrics like VO2 max,” Marinelli says.

After feeding the measurements from the study participants into this predictive model, known as PhenoMol, the researchers were able to identify more than 100 biomarkers linked to performance on the ACFT. Fitness predictions based on these biomarkers were much more accurate than those of a model that correlated biomarkers with performance on the ACFT without taking network connections into account. Additionally, PhenoMol performed similarly to a model that predicted participants’ fitness based on measurements of their VO2 and lean muscle mass.

Cellular pathways

The researchers found that the biomarkers identified by PhenoMol clustered into several different cellular pathways. Those include pathways involved in blood coagulation and the complement cascade — a part of the immune system involved in clearing damaged cells. Those systems likely help with recovery from tissue injury and stress response during exercise, Fraenkel says.

Another prominent cluster involves molecules related to the urea cycle, which is responsible for eliminating the ammonia that results from the breakdown of proteins. The model also identified biomarkers that are linked with the function of mitochondria (the organelles that generate energy within cells).

Fraenkel now hopes to dig deeper into which markers show someone’s current fitness, and which might reveal what their potential fitness levels could be. This could help to reveal potential strengths that might not show up in traditional fitness tests, he says.

That kind of prediction could be useful not only for athletic training, but also for other people who are recovering from an injury or disease, or people experiencing the effects of aging. For example, using this approach in different populations might provide useful information for an elderly person after a stroke, since such events often require months of therapy to regain significant mobility.

“This has relevance for the military and for sports teams, but also in a lot of normal life situations where maybe someone is going through rehabilitation for some injury or disease and they’ve hit a wall,” Fraenkel says. “Or during aging, you may be able to see when somebody’s losing capacity or when they have more capacity than they’ve been able to actualize.”

Molecular markers of fitness could also be used in clinical trials to rigorously test the potential benefits of popular food supplements and fitness programs, he adds.

To make the testing process simpler, the researchers would like to narrow down their pool of biomarkers to a handful that could be easily measured from a blood sample using a single method suitable for widespread use.

The research was developed with funding from the Defense Advanced Research Projects Agency (DARPA), which states that the views, opinions, or findings expressed are those of the authors and should not be interpreted as representing the official views or policies of the U.S. government.