That has left scientists with a difficult question: Could humans gain some of the longevity benefits of calorie restriction without experiencing those harmful effects? A new study, published in Nature Aging, points to a possible answer involving an immune protein called complement component 3 (C3).

Yale researchers have previously shown that people who followed moderate calorie restriction, cutting calorie intake by 14% for two years, developed stronger immune defenses without experiencing problems related to growth or reproduction.

“This concept demonstrates that aging is actually malleable and a process that can be targeted,” says senior author Vishwa Deep Dixit, PhD, Waldemar Von Zedtwitz Professor of Pathology, professor of immunobiology and of comparative medicine, and director of the Yale Center for Research on Aging (Y-Age) at Yale School of Medicine.

Calorie Restriction Lowers an Inflammation-Linked Protein

For the new study, Dixit and his colleagues at YSM examined plasma samples from 42 people who participated in a National Institutes of Health-funded two-year study called the Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy or CALERIE.

“It’s the only trial of its kind that has been done with such rigor and control and demonstrates relevance to human physiology,” Dixit says. During the trial, participants reduced their calorie intake by 11 to 14% without feeling deprived.

The researchers measured more than 7,000 proteins across plasma samples collected over time. One stood out: complement component 3 (C3), an immune protein whose levels fell significantly after calorie restriction.

C3 drew particular attention because earlier research has suggested that activation of the complement system, a network of proteins that helps defend the body against pathogens, may contribute to chronic inflammation. That persistent inflammation is considered a major feature of aging and many age-associated diseases.

“But the causal effects of C3 in aging and chronic inflammation have not been identified. So, we were very excited to find that in our study,” says Hee-Hoon Kim, PhD, a postdoctoral associate in the Dixit lab and a co-first author of the paper.

Fat Tissue Emerges as a Key Source of C3

By comparing protein levels before and after two years of calorie restriction, the team found that white adipose tissue, the main form of fat tissue in mammals, appeared to be the primary tissue affected by the dietary change.

The researchers then tested the pattern in animals. As they had seen in human plasma, C3 expression rose with age in mice. Additional biochemical testing showed that visceral white adipose tissue was a major source of the age-related increase in C3.

“We were not expecting that because these proteins are mainly synthesized in the liver,” says Manish Mishra, PhD, a postdoctoral associate in the Dixit lab and a co-first author of the study.

Single-cell RNA sequencing allowed the researchers to narrow the source further. They found that C3 was being produced by age-associated macrophages, essential white blood cells located within adipose tissue.

“This whole process was unknown in the beginning,” Mishra says. “Just to narrow it down to the subtypes of macrophages responsible for this complement protein production was very challenging.”

Macrophages are among the immune system’s first responders and are best known for engulfing pathogens. They also play an important role in maintaining normal tissue function, Dixit adds.

Could the Benefits Be Independent of Weight Loss?

The next question was whether reducing C3 could provide benefits even without weight loss.

The researchers initially thought that losing adipose tissue might itself reduce C3 production and contribute to healthier aging. Most participants in the study lost about 18 pounds after two years of moderate calorie restriction.

However, when the researchers compared changes in body mass index with changes in complement protein levels, they found no relationship between the amount of weight lost and the decline in those proteins.

“This suggests that calorie restriction has a beneficial effect that is unique to adipose tissues and is likely independent of weight loss,” Kim says.

That raised the possibility that some of the biological benefits of calorie restriction might be reproduced without requiring people to lose weight.

Blocking C3 Reduces Inflammation in Mice

To test that idea, the researchers used a drug to inhibit C3 activation in mice, mimicking one of the effects of calorie restriction. The animals developed less age-related inflammation.

According to Dixit, the result illustrates how biological systems that are useful earlier in life can become harmful later. This concept, known as antagonistic pleiotropy, was proposed by biologist Peter Medawar in 1952 as an explanation for aspects of aging.

Growth hormone offers one example. It is essential during early development, but later in life it may also contribute to cancer.

C3 and similar proteins evolved to protect the body against infection. But because humans now live far longer than their ancestors, some of those same protective mechanisms may eventually begin contributing to disease. Dixit says reducing excessive C3 activity could potentially help extend health span.

Researchers Explore Existing Drugs as an Aging Target

The team is now studying whether FDA-approved inhibitor drugs could be used to suppress C3 production and potentially slow aspects of aging in humans.

The goal is not to eliminate the complement system entirely, because it remains essential for fighting infections.

“The idea is not to remove complement systems that are required for us to fight infections,” Dixit says. “Instead, the goal is to restore the balance.”

Now, researchers have confirmed that a previously unrecognized Asian pangolin species, Manis aurita, has been living in Nepal and Northern India. The findings, published in Communications Biology, clarify how different pangolin species are related, where they live, and how they can be distinguished. That information could also help authorities identify where illegally traded pangolins are being hunted and strengthen efforts to stop poaching.

“We can’t protect what we do not know, and now that we have confirmed that this other species of pangolin exists, we can use that information to help protect these endangered animals,” says Anderson Feijó, the Negaunee Assistant Curator of Mammals at the Field Museum and co-corresponding author of the study.

“This finding marks the culmination of more than five years of research that began in Nepal, where we first documented evidence suggesting that Himalayan pangolins represented a distinct evolutionary lineage,” says Narayan Koju, a researcher at the Nepal Engineering College at Pokhara University and the study’s first author. “The confirmation of Manis aurita as a valid species demonstrates the importance of long-term research, international collaboration, and museum collections. Most importantly, it provides a strong scientific basis for conservation planning, wildlife forensics, and efforts to protect one of the world’s most trafficked mammals from extinction.”

Untangling the Pangolin Family Tree

The classification of these Himalayan pangolins had already begun to change in 2025. That year, another research team determined that animals previously grouped together as Chinese pangolins actually represented two species. One occurs mainly in China, while the other inhabits the Himalayan foothills across parts of Nepal, India, Bhutan, and Myanmar. The researchers named the mountain-dwelling form Manis indoburmanica, or the Indo-Burmese pangolin.

But scientific naming follows a rule of priority: when the same species has been given more than one scientific name, the earliest valid name takes precedence.

At the time, Feijó and his colleagues were already conducting a decade-long investigation into pangolin evolution. Their work combined DNA evidence with physical characteristics to determine how many pangolin species exist and how those species are related.

During that research, they encountered records of Manis aurita, a pangolin described in 1836. Over time, M. aurita had been reclassified as a subspecies of the Chinese pangolin.

“This left us with a core taxonomic riddle: what is the relationship between indoburmanica and aurita? Are they the same species or different species?” says Kai He, another of the paper’s co-corresponding authors and a researcher at the South China Biodiversity Research Center at Guangzhou University. “The ultimate, most thrilling piece of the puzzle came from the Natural History Museum in London. Thanks to their incredible expertise and assistance, the NHM team successfully sequenced the DNA directly from the historical type specimen of the Nepalese subspecies (aurita). This specimen dates back to 1836, making it nearly 190 years old.”

DNA From 1836 Provides the Answer

Genetic material recovered from the historic museum specimen settled the question. Modern Himalayan pangolin samples matched aurita, showing that the animals described in 2025 as M. indoburmanica were actually members of the species first named M. aurita.

As a result, M. aurita is the correct scientific name.

“This taxonomic clarification provides a crucial scientific basis for combating illegal poaching and lays the groundwork for protecting this cryptic endangered species,” says Yan Hua, a co-corresponding author of the study and researcher at the Guangdong Academy of Forestry.

The Himalayan pangolin M. aurita (briefly formerly known as M. indoburmanica) differs from the Chinese pangolin in several subtle but important ways.

“Compared to the Chinese pangolin, the Himalayan pangolin has a bigger body, a longer tail, and smaller ears,” says Feijó. The revived name aurita itself refers to the animal’s distinctive ears.

The two species are also separated geographically. Their known ranges do not overlap. For critically endangered animals, especially those facing intense pressure from poaching, understanding exactly which species lives where can be essential for conservation.

A New Tool Against Pangolin Trafficking

Pangolin scales are believed to be a powerful aphrodisiac in traditional Chinese medicine practices, helping drive a large illegal trade in the animals. Preventing that trafficking is difficult in part because authorities often encounter scales rather than intact animals.

“In the marketplaces you basically only find pangolin scales, not the whole animals, which makes it hard to know which species are being hunted and where they are coming from,” says Feijó.

The DNA methods used in the new research could make those seizures much more informative. Conservation scientists may be able to analyze confiscated scales, determine which pangolin species they came from, and then use that information to identify regions where poaching pressure is especially intense.

That could allow conservationists and law enforcement agencies to work backward from illegally traded material to the populations being targeted.

A clearer understanding of species boundaries can also improve efforts to return pangolins to areas where they once lived. Reintroduction programs need to ensure that they are releasing the appropriate species into the appropriate geographic range.

“Before, you might have introduced Chinese pangolins into Nepal, because you didn’t know the difference,” says Feijó. “By defining the differences between the species and the limits of where each species is found, we can make better conservation decisions.”

Museum Collections Reveal Hidden Biodiversity

The researchers say these practical conservation advances would have been much harder without natural history museums. Museum collections preserve pangolin specimens collected more than a century ago, giving scientists access to animals from locations and populations that can be extremely difficult to sample today.

“Using museum collections allows us to have access to more individuals across the species’ range,” says Feijó. “If you only rely on fresh material, since the animals are so rare to find in the wild, this greatly limits the information that you can gather. We used collections to have a more complete sampling of the species. It’s a big advantage to have this resource available as a repository of material that we can look back and keep learning from.”

This study was contributed to by scientists from Guangzhou University, Nepal Engineering College, Pokhara University, the Chinese Academy of Sciences, University of Washington, the Smithsonian National Museum of Natural History, the University of Sevilla, the Guangdong Academy of Forestry, Tribhuan University, Aspect Ecology Oxfordshire, the Chinese Wildlife Forensic Science Service, Chengdu University of Traditional Chinese Medicine, and the Field Museum.

The newly separated tabular iceberg broke away from Petermann Glacier’s floating ice tongue and may be as much as 150 meters thick. Its surface area is roughly comparable to Manhattan Island, giving scientists a rare opportunity to observe how enormous Arctic ice masses develop, move through the ocean and eventually fragment.

The event was identified by Adam Garbo, a PhD student in glaciology at uOttawa’s Department of Geography, Environment and Geomatics. The discovery is part of an ongoing collaboration involving the University of Ottawa, the University of Stirling, Environment and Climate Change Canada, Lancaster University, and the University of Leeds.

Satellite Monitoring Revealed Years of Growing Instability

Scientists have been tracking changes at Petermann Glacier with long-term satellite observations since 2019. Over that period, they closely followed the condition of the glacier’s floating ice tongue, recording the expansion of fractures and watching for signs that a major section might eventually break away.

“Petermann Glacier has long been one of Greenland’s largest remaining ice tongues,” says Garbo. “We’ve anticipated this break for years, and seeing it finally happen is remarkable.”

Images collected by the European Space Agency’s Sentinel-1 mission showed clear signs of deterioration along the centerline of the ice tongue on August 3. By 20:00 UTC on August 4, the new ice island had fully separated from the glacier’s eastern side.

Rare Arctic Ice Islands Offer a Window Into Polar Change

Large, flat-topped icebergs are relatively common around Antarctica, but comparable ice islands are much less frequently seen in the Arctic. Their rarity and longevity make them especially valuable to researchers studying glacier retreat, changing ocean conditions and the risks posed by drifting ice in polar regions.

“While large, tabular icebergs are relatively common in the Southern Ocean that surrounds the Antarctic Ice Sheet, Arctic ice islands are far rarer,” explains Dr. Anna Crawford of the University of Stirling. “By studying Arctic ice islands, we will gain knowledge that can be transferred across Polar regions.”

Scientists do not expect the August calving event to be the last major change at Petermann Glacier. Two additional large sections of the floating ice tongue are expected to detach in the near future as rifts that have been developing for years continue to cut through the ice.

Those future ice islands are projected to measure about 94 km² and 84 km². If both break away, the three calving events combined would remove approximately 254 km² from Petermann Glacier’s ice tongue, reducing it by about 22 percent.

Drifting Ice Could Create Hazards for Arctic Shipping

The newly formed ice island is important not only for scientific research, but also for marine safety. Massive pieces of floating ice can remain intact for years as they drift, then gradually fracture into smaller sections that may become difficult to track.

Environment and Climate Change Canada is monitoring the ice island’s movement, as it has done following previous Arctic ice shelf calving events, while evaluating potential risks to vessels and offshore infrastructure.

“These are thick blocks of ice that can drift for years,” specifies Dr. Abigail Dalton of the Canadian Ice Service, Environment and Climate Change Canada. “Over time, they fracture into smaller, harder-to-track pieces that pose hazards to vessels and resource operations.”

Garbo and his collaborators plan to continue following the aftermath with satellite imagery, aerial observations and tracking data. Their work is part of a broader effort to better understand the processes responsible for the calving and retreat of Arctic ice shelves.

Researchers at Stanford Medicine and collaborating institutions have now developed a strategy aimed at overcoming those obstacles. Their approach transforms natural killer cells, a type of immune cell known for rapidly attacking abnormal cells, into a specialized tissue resident form that can move into solid tumors and destroy cancer cells.

“We show that these tissue-resident natural killer cells infiltrate into the solid tumors much better than conventional natural killer cells. It was very reproducible, very striking and very clear,” said John Sunwoo, MD, the Edward C. and Amy H. Sewall Professor in the School of Medicine and senior author of the study published last month in Science Translational Medicine.

The study’s co-lead authors are Nina Horowitz, PhD, a former doctoral student in otolaryngology; Imran Mohammad, PhD, a postdoctoral fellow in the Sunwoo lab; and June Ho Shin, PhD, a senior scientist in the Sunwoo lab.

Natural Killer Cells Show Promise Against Solid Tumors

The team tested the experimental therapy in mice and found that the modified natural killer cells slowed the growth of several kinds of solid tumors. The effect became stronger when the cells were paired with an antibody treatment that helps guide natural killer cells toward cancer cells.

Natural killer cells may also offer an important practical advantage. They do not typically trigger an immune reaction when transferred from one person to another. Most current immune cell therapies must be individually manufactured from a patient’s own cells, but a treatment based on these modified natural killer cells could potentially be produced in large batches, frozen and made available to many patients.

“It would be almost an off-the-shelf drug,” Sunwoo said. “It could make cell therapy much more accessible to a wider variety of patients.”

Why Tissue Resident Immune Cells Matter

Natural killer cells were first identified in the 1970s. Their name comes from their ability to rapidly recognize and destroy abnormal cells, including cancer cells and cells infected by viruses. Unlike other white blood cells, such as B cells and T cells, natural killer cells do not need to encounter a specific target beforehand, allowing them to respond quickly.

Historically, much of immunology has centered on immune cells circulating in the bloodstream, including B cells, T cells, and natural killer cells. These cells travel throughout the body searching for infection and disease. Some, however, eventually settle inside tissues and take on functions tailored to their local environment.

“For a long time, the study of immunology and disease in humans was concentrated on the blood immune cells,” Sunwoo said. “With the advancement of tools and bioinformatics, we are now starting to look more at what’s going on in tissue. For most immune cells, the tissue is where the action is.”

Tissue resident natural killer cells are found in locations including the skin, mucous membranes, lungs and liver. Scientists have struggled to understand exactly what they do because previous studies have produced conflicting results. Some suggested these cells were relatively weak killers and could even suppress immune activity, while others found that they were highly effective at destroying target cells.

“They may adopt different functions based on certain cues in the microenvironment and in the tissue, and differentiate into a certain kind of sub-population,” Sunwoo said.

In some circumstances, immune-suppressing tissue-resident natural killer cells are beneficial. During early pregnancy, for example, these cells in the uterine lining help prevent the immune system from attacking fetal cells and support placental growth. Cancer treatment, however, requires the more aggressive type.

Finding the Right Cellular Recipe

Evidence suggested that there were two distinct forms of tissue-resident natural killer cells, but researchers did not fully understand how they developed or why their behavior was so different.

To investigate, Sunwoo’s team isolated circulating natural killer cells from human blood donors and exposed them to different combinations of cellular signals.

One important ingredient was TGF-b, transforming growth factor beta. This signaling protein is produced by many cell types, including tumor cells, and plays a role in determining how cells develop. The researchers found, however, that the amount and duration of the signal were critical.

“It’s a Goldilocks kind of thing where if you give just enough of a TGF-b signal, then the natural killer cells become tissue resident with strong toxic activity against malignant cells. If you give too much TGF-b, they’re still tissue resident, but they’re inhibited and dysfunctional, and they don’t kill,” Sunwoo said. “You need it to be presented to the natural killer cells in just the right amount and in just the right manner.”

The experiments showed that TGF-b was required to turn natural killer cells into a tissue resident form. But prolonged exposure produced cells that were poor killers.

A different approach worked much better. The researchers briefly exposed natural killer cells to short-lived human epithelial tumor cells that provided a temporary burst of active TGF-b. That produced tissue-resident natural killer cells with strong tumor-killing activity.

Direct physical contact with the epithelial tumor cells was also essential. Simply placing the cells nearby was not enough, suggesting that additional activating signals were involved.

“These two tissue-resident natural killer cell populations look very similar, and they have some of the same requirements, but their function seems to be on opposite ends of the spectrum,” Sunwoo said.

What Makes the Strongest Killer Cells Different

The team then compared the two types of tissue-resident natural killer cells in detail.

Both types displayed the surface proteins CD49a and CD103. Only the highly effective cancer-killing cells, however, expressed CD39.

The stronger cells also contained more of the molecular machinery needed to kill targets. This included perforin, a protein that creates holes in target cells, and granzyme A, a toxic molecule delivered through those openings.

Slowing Tumor Growth in Mice

Once the researchers established a reliable method for producing the more aggressive natural killer cells, they tested how well the cells could enter tumors.

In laboratory experiments, the modified cells successfully infiltrated tumor organoids grown in dishes. When injected into mice, they slowed the growth of several types of solid tumors over periods of days and weeks. These included tumors derived from human melanoma and head and neck squamous cell carcinoma.

The strongest results came when the modified natural killer cells were combined with cetuximab, a monoclonal antibody that helps mark certain cancer cells for immune attack.

Cetuximab is approved to treat metastatic colorectal cancer and advanced head and neck squamous cell carcinoma, although Sunwoo noted that it does not work especially well when used alone.

A single dose of the combination therapy suppressed tumor growth in mice much more effectively over one month than either treatment by itself. The researchers also did not observe apparent adverse effects.

“Even at day 30, when the other mice were sick, the mice that received the combination seemed very healthy,” Sunwoo said, though he cautioned against extrapolating too much from mice to humans, adding, “This was just proof of concept.”

Toward an Off-the-Shelf Cell Therapy

Sunwoo and his colleagues are now preparing a Phase I clinical trial to test the combination therapy in people with advanced squamous cell carcinoma. The trial could begin by the end of the year, pending approval from the Food and Drug Administration.

Sunwoo has also developed and applied to patent a method for producing and expanding large numbers of the modified cells, technically known as cytotoxic tissue-resident natural killer cells.

According to the researchers, natural killer cells collected from a single donor could produce about 20 treatment doses in roughly two weeks.

“They’ll be cryopreserved, so we can make a bunch of doses and give it to different patients,” Sunwoo said. “There would be no delay.”

Researchers from Ohio State University and Washington University School of Medicine contributed to the work.

The study received funding from the National Institutes of Health (grants R35DE030054, K22CA282364 and R25DC020174), the Tai Tsun Wu Research Fund for Natural Killer Cell Immunotherapy and the Stanford Bio-X Fellowship.

In a study published in ACS Catalysis, an international team that included Dr. Christopher Parlett, Xinyue Zhou, and Yutao Jiang from the Department of Chemical Engineering developed a highly efficient “single-atom catalyst.” The researchers also determined, at the molecular level, how the catalyst breaks the strong chemical bonds that help hold lignin together.

The catalyst contains individual ruthenium atoms embedded within a nitrogen-doped carbon material. By keeping the ruthenium atoms isolated, the design can deliver strong catalytic performance while requiring only very small amounts of metal, improving efficiency compared with conventional systems.

Revealing How the Catalyst Breaks Down Lignin

One persistent obstacle in lignin research has been identifying exactly which parts of a catalyst are responsible for breaking the material’s unusually strong chemical bonds. Without that information, researchers have had limited guidance for designing more effective catalysts.

The team found that a particular atomic arrangement known as a “Ru-N₄ site” is especially important. These sites activate oxygen molecules and help trigger the breaking of both carbon-oxygen and carbon-carbon bonds within lignin.

Using a combination of laboratory experiments and computational modeling, the researchers were able to reconstruct the process in greater detail. The catalyst first activates oxygen, producing highly reactive species. Those species then attack the lignin structure and split it into smaller molecules.

High Conversion With Milder Conditions

When tested under optimized conditions, the catalyst converted nearly all of the model lignin compounds and generated high yields of valuable chemical products, including phenol.

The process also works under relatively mild conditions and does not require harsh chemicals. That combination could make the approach useful for developing more sustainable methods of chemical manufacturing.

The researchers went beyond simplified model compounds and tested the catalyst on real lignin collected from several biomass sources. It successfully converted those samples into useful aromatic compounds that could potentially become building blocks for fuels, plastics, and other materials.

A Potential Path Toward Biomass-Based Chemicals

The findings provide a more detailed picture of how single-atom catalysts operate during biomass conversion. That understanding could serve as a guide for developing more efficient catalytic systems in the future.

“Understanding exactly how these catalysts work at the atomic level allows us to design better materials for converting renewable resources into valuable chemicals,” said Dr. Christopher Parlett, Lecturer in Chemical Engineering.

By making it easier to upgrade lignin and convert it into higher-value products, the research could support a broader shift away from traditional linear petroleum-derived chemical production and toward a more circular, biomass-based economy.