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.