“In worms, flies, and mice, calorie restriction can slow biological processes of aging and extend healthy lifespan” says senior author Daniel Belsky, PhD, associate professor of epidemiology at Columbia Mailman School and a scientist with Columbia’s Butler Aging Center. “Our study aimed to test if calorie restriction also slows biological aging in humans.”

The CALERIE™ Phase-2 randomized controlled trial, funded by the US National Institute on Aging, is the first ever investigation of the effects of long-term calorie restriction in healthy, non-obese humans. The trial randomized 220 healthy men and women at three sites in the U. S. to a 25 percent calorie-restriction or normal diet for two years.  CALERIE™ is an acronym for ‘Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy’.

To measure biological aging in CALERIE Trial participants, Belsky’s team analyzed blood samples collected from trial participants at pre-intervention baseline and after 12- and 24-months of follow-up. “Humans live a long time,” explained Belsky, “so it isn’t practical to follow them until we see differences in aging-related disease or survival. Instead, we rely on biomarkers developed to measure the pace and progress of biological aging over the duration of the study.” The team analyzed methylation marks on DNA extracted from white blood cells. DNA methylation marks are chemical tags on the DNA sequence that regulate the expression of genes and are known to change with aging.

In the primary analysis Belsky and colleagues focused on three measurements of the DNA methylation data, sometimes known as “epigenetic clocks”. The first two, the PhenoAge and GrimAge clocks, estimate biological age, or the chronological age at which a person’s biology would appear “normal”. These measures can be thought of as “odometers” that provide a static measure of how much aging a person has experienced. The third measure studied by the researchers was DunedinPACE, which estimates the pace of aging, or the rate of biological deterioration over time. DunedinPACE can be thought of as a “speedometer”.

“In contrast to the results for DunedinPace, there were no effects of intervention on other epigenetic clocks,” noted Calen Ryan, PhD, Research Scientist at Columbia’s Butler Aging Center and co-lead author of the study. “The difference in results suggests that dynamic ‘pace of aging’ measures like DunedinPACE may be more sensitive to the effects of intervention than measures of static biological age.”

Our study found evidence that calorie restriction slowed the pace of aging in humans” Ryan said.  “But calorie restriction is probably not for everyone. Our findings are important because they provide evidence from a randomized trial that slowing human aging may be possible. They also give us a sense of the kinds of effects we might look for in trials of interventions that could appeal to more people, like intermittent fasting or time-restricted eating.”

A follow-up of trial participants is now ongoing to determine if the intervention had long-term effects on healthy aging. In other studies, slower DunedinPACE is associated with reduced risk for heart disease, stroke, disability, and dementia.  “Our study of the legacy effects of the CALERIE™ intervention will test if the short-term effects observed during the trial translated into longer-term reduction in aging-related chronic diseases or their risk factors,” says Sai Krupa Das, a senior scientist and CALERIE investigator who is leading the long-term follow up of CALERIE™ participants.

DunedinPACE was developed by Daniel Belsky and colleagues at Duke University and the University of Otago. To develop DunedinPACE, researchers analyzed data from the Dunedin Longitudinal Study, a landmark birth cohort study of human development and aging that follows 1000 individuals born in 1972-73 in Dunedin, New Zealand. Researchers first analyzed the rate of change in 19 biomarkers across 20 years of follow-up to derive a single composite measure of the Pace of Aging. Next, the researchers used machine-learning techniques to distill this 20-year Pace of Aging into a single-time-point DNA methylation blood test. The values of the DunedinPACE algorithm correspond to the years of biological aging experienced during a single calendar year, providing a measure of the pace of aging.

The study was supported by US National Institute on Aging grant R01AG061378 and also utilized resources provided by the CALERIE Research Network (R33AG070455) and the Dunedin Study (R01AG032282). Coauthors received additional support from the American Brain Foundation, and NIH grants P30AG028716, R01AG054840, R33AG070455, CIHR RN439810, R01 AG071717, R03AG071549 U01AG060906.

In recent years, scientists have used satellite imagery, earthquake data and GPS to search for ground deformation near active volcanoes, but those techniques can be inaccurate in locating the depth of magma storage.

By finding microscopic, carbon dioxide-rich fluids encased in cooled volcanic crystals, scientists can accurately determine — within one hundred meters — where magma is located.

“A fundamental question is where magma is stored in Earth’s crust and mantle,” said Esteban Gazel, professor of engineering and lead author of the study, published in Science Advances. “That location matters because you can gauge the risk of an eruption by pinpointing the specific location of magma, instead of other signals like hydrothermal system of a volcano.”

Gazel notes that speed and precision are essential. “We’re demonstrating the enormous potential of this improved technique in terms of its rapidity and unprecedented accuracy,” he said. “We can produce data within days of the samples arriving from a site, which provides better, near real-time results.”

In volcanic events, magma reaches the Earth’s surface, and it erupts as lava and — depending on how much gas it contains — could be explosive in nature. When deposited as part of the fallout of the eruption, fragmented fine-grained material — called tephra — can be collected and evaluated.

Gazel and doctoral student Kyle Dayton deduced how to use inclusions of carbon dioxide-rich fluids trapped within olivine crystals to precisely indicate depth, as the carbon dioxide density of these inclusions is controlled by pressure.

These fluids can be measured quickly using an instrument to determine — in terms of kilometers — how far down the magma was stored and the depth of the scorching reservoir.

Gazel and Dayton joined a small, elite team of international researchers to study the Cumbre Vieja volcano on La Palma in the Canary Islands. Gazel and Dayton picked through tephra to find crystals, which in turn provide data to improve eruption models and forecasts.

The findings result from a collaboration between the University of Colorado Boulder and three South Africa-based institutions: the University of Venda, Lajuma Research Centre and the conservation organization the Endangered Wildlife Trust (EWT). They take an almost forensic look at what is killing wild animals in South Africa. The country is home to five species of non-human primates, including greater (Otolemur crassicaudatus) and southern lesser (Galago moholis) bushbabies. These primates spend most of their lives in trees, and some are so small they can fit in the palm of your hand.

In one study, scientists led by Birthe Linden at Lajuma analyzed hundreds of cases in which non-human primates had been killed on roads or around power lines across the country. In a companion paper, the researchers explored the growing risks that domestic dogs pose to the animals.

The research shows that the threats facing the world’s monkeys, apes and other non-human primates aren’t always easy to see, particularly for lesser-studied animals like bushbabies.

“Bushbabies, especially, are an example of species that may be having problems, but we don’t know what they are until we go looking,” said Michelle Sauther, co-author of the two studies and professor of anthropology at CU Boulder.

For her, the results border on personal.

In the process of studying bushbabies in South Africa for more than a decade, Sauther and her colleagues got to know one male, in particular — a greater bushbaby with one eye who the team nicknamed Bruiser because he reminded them of an old prize fighter.

Then in 2019 Bruiser, who had bad and missing teeth, tried to move on the ground to reach a fig tree with easy-to-grab fruit. A pet dog found and killed him.

“These are small stories,” Sauther said. “They’re not the big stories of conservation, but they really do matter, especially as we have no good data on bushbaby mortality and thus cannot easily judge their conservation status.”

They’re also small stories that likely touch almost all non-human primate species, not just in South Africa but across the continent.

“We found that all South African non-human primates are in one way or the other impacted by human linear infrastructure, such as power lines or roads,” Linden said.

Roadkill on the rise

Linden, a primatologist from South Africa, first became interested in the hidden dangers facing primates on her almost daily drives to the University of Venda in South Africa’s Soutpansberg Mountains.

She kept seeing samango monkeys (Cercopithecus albogularis) run over on the side of the road. These monkeys are listed in the “Red List of Mammals of South Africa, Swaziland and Lesotho” as “vulnerable,” one step up from “endangered.”

“It’s one stretch where the road is quite close to indigenous forest, which is where samango monkeys typically live,” Linden said.

She wondered if a lot more non-human primates could be dying as roadkill than researchers suspected. South Africa is home to more than 675,000 miles (1,090,000 kilometers) of roads and power lines — and the number keeps climbing.

To explore this pervasive threat, Linden and her colleagues drew from a wide range of data sources. They include Road Watch, a citizen science app released by the EWT that allows anyone in South Africa to upload reports of roadkill. In all, the team gathered 483 examples of primates killed on roads or around power lines, some dating back to the late 1990s. Species included the two bushbabies, samango monkeys, chacma baboons (Papio ursinus) and vervet monkeys (Chlorocebus pygerythrus).

Next up, Frank Cuozzo of the Lajuma Research Centre and a research fellow at the University of Pretoria’s Mammal Research Institute led the group in exploring a different kind of peril: domestic dogs. The researchers tracked down 13 reports of greater bushbabies like Bruiser killed by dogs in South Africa since 2014. In one case, humans intentionally released dogs to hunt down a bushbaby that had gotten too close to town.

“These reports are clearly a sliver of what’s actually happening,” said Cuozzo who earned his doctorate in biological anthropology from CU Boulder in 2000. “It’s happening in the towns and suburban areas, in the rural areas, the reserve areas, and it’s happening far more than anyone would think.”

Why did the monkey cross the road?

The researchers aren’t sure how big of a dent roads, power lines and domestic dogs are making in non-human primate numbers in South Africa or surrounding nations. But they argue that these deaths are important to follow — especially for animals already struggling to survive amid climate change and habitat loss.

Wendy Collinson-Jonker, co-author of the infrastructure study and a researcher at the EWT, noted that these problems are widespread, but the fixes may be surprisingly simple.

Studies have shown, for example, that monkeys and other forest critters can hop across roads safely on “canopy bridges,” such as a rope bridge hanging between trees.

Humans can also keep dogs away from primates by being careful to not leave food out, especially at night.

“We know the solutions,” Collinson-Jonker said. “It’s a case of now getting them implemented.”

As for Bruiser the bushbaby, Sauther noted that his story ended with a small bit of consolation. The team was able to recover his body and collected X-rays that helped reveal a deeper picture of his more than a decade of life — down to the arthritis building up between his joints that likely led him to climb down to the ground.

“We were able to document his whole life story,” Sauther said. “We knew him right to the end.”

That’s the finding of a study by scientists from Penn’s School of Veterinary Medicine, published in the journal Prion. Using feces samples from CWD-positive deer and deer in which CWD was not detected, the researchers trained the dogs to identify the odor of CWD, alerting their handlers to its presence in the lab and in the field.

“We were already quite certain that the dogs could detect the volatile organic compounds released by chronic wasting disease in feces,” says Amritha Mallikarjun, a postdoctoral researcher in Penn Vet’s Working Dog Center and lead author on the study. “Not only did we show this was possible, but we also answered a second, more interesting question, which is, Can they detect the disease in a simulated field setting, as they would if we were using the dogs to find the disease in the landscape of a forest or on a deer farm?”

The dogs indeed could, with enough accuracy to suggest that detection dogs could be a useful strategy in the fight to manage CWD.

“We learned a lot through the study and are now set up well to continue refining our training,” says Cynthia Otto, the senior author on the study and director of the Working Dog Center.

CWD is a disease that affects a variety of deer species, including white-tailed deer, mule deer, and elk. Always fatal and highly contagious, the disease can hide away in an affected animal for a year or two before symptoms manifest: the deer losing weight — “wasting” — and developing neurological signs, like stumbling and drooling. No cure or treatment exists.

The disease has been in Pennsylvania since 2012, and the state has invested significantly in trying to contain it, with several tools in place for keeping tabs on its spread. One hurdle is figuring out which deer are affected. A healthy-looking but infected animal could shed prions, malformed and infectious proteins, for many months or even years before succumbing to the illness. What’s more, prions are known to bind to soil, potentially contaminating the land on which other animals may roam.

The gold-standard diagnostic test can only be performed after death by assessing an affected animal’s brain. Some alternative tests have been trialed that involve taking a biopsy from a potentially infected animal while it’s still alive, but deer are known to be highly stressed by being captured, and collecting these samples can be physically and logistically difficult for the people involved as well.

The Working Dog Center, the Pennsylvania Department of Agriculture, and the Wildlife Futures Program, a partnership between Penn Vet and the Pennsylvania Game Commission, were well positioned to try to contribute an additional technique for managing the disease: dogs and their highly sensitive noses. Ideally, dogs trained to discern CWD-positive from CWD-not-detected feces in a forest or deer farm could help state agencies and private landowners understand whether further testing or management would be needed to keep their land and herds free from the disease.

First, scientists had to prove the dogs could make this distinction reliably. The Working Dog Center began by enlisting three dogs from their citizen science program — Labrador retrievers Charlie and Kiwi and Finnish spitz Jari — to train on the Center’s “scent wheel,” a contraption equipped with eight ports, each containing a specific substance or scent.

The dogs proved adept at this task. Once they had been trained, using samples provided by the U.S. Department of Agriculture and processed by the Wildlife Futures Program, the dogs responded with great specificity, passing by the not-detected samples 90-95% of the time. Their sensitivity, however, was not as strong, alerting to just 40% of the positive samples. Overall, the researchers found that the dogs spent more time at the ports containing positive samples than those with not-detected samples, suggesting that they perceived a difference even if they didn’t always produce the trained response, such as a bark or sitting down when they smelled the positive sample.

Moving toward a more naturalistic setting, the researchers then experimented with having the dogs and their handlers try to discern CWD-positive samples placed throughout a large, privately owned field. To avoid contaminating the soil or having the dogs come in contact with the samples, two-gram samples of feces were placed in jars with mesh lids to allow the odor to waft out and then partially buried in the ground in different areas.

The researchers observed that the dogs responded to the positive samples more often than the not-detect samples in the field trial. In total, they detected eight of 11 positive samples in the field, with a false negative rate of 13%. Both handlers and dogs seemed to improve as they went, their accuracy increasing after their first field search.

“Given the amount of time that we trained these dogs and the novel environment, not to mention the fact that these are pet dogs and not trained search dogs, our results are promising,” says Mallikarjun. “As we move forward and work with dogs that are specifically trained to search in a field setting and devote their entire lives to detecting this odor, they are going to do an even better job.”

That’s a step the Wildlife Futures Program is already taking, with canine handlers training “professional” detection dogs how to canvas fields and forests, searching for CWD.

The researchers believe that, while dogs don’t represent a silver bullet in the fight against CWD, they may prove useful as an early warning system, helping fill gaps in knowledge from other monitoring systems and management approaches.

“These dogs could increase the odds of catching an outbreak early,” says Lisa Murphy, a study co-author and co-director of the Wildlife Futures Program.

The Penn Vet team is also collaborating with other groups not only to work with detection dogs but also to identify the odor dogs may be responding to in order to develop other systems for early detection. The lessons learned could be broadly useful.

“If we’re able to tap into what we’ve learned with chronic wasting disease and apply it to other issues in agriculture and conservation, these dogs could be a major asset,” Otto says.

Amritha Mallikarjun is a postdoctoral fellow in the University of Pennsylvania School of Veterinary Medicine.

Lisa Murphy is resident director of PADLS New Bolton Center, a professor of toxicology, associate director of the Institute for Infectious and Zoonotic Diseases, and co-director of the Wildlife Futures Program at Penn’s School of Veterinary Medicine.

Cynthia Otto is a professor of working dog sciences and sports medicine and director of the Working Dog Center in Penn’s School of Veterinary Medicine.

Mallikarjun, Murphy, and Otto’s coauthors were Penn Vet’s Ben Swartz, Sarah A. Kane, Michelle Gibison, Isabella Wilson, Amanda Collins, Madison B. Moore, Ila Charendoff, and Julie Ellis and the U.S. Department of Agriculture’s Tracy Nichols. Mallikarjun is corresponding author on the study.

The work was supported by the Pennsylvania Department of Agriculture and the Wildlife Futures Program at the University of Pennsylvania School of Veterinary Medicine.