Ecological imbalance

Earth and environmental scientists at ETH Zurich led an international team of researchers from the University of Arizona, University of Leeds, CNRS Toulouse, and the Swiss Federal Institute for Forest Snow and Landscape Research (WSL) in a study on how vegetation responds and evolves in response to major climatic shifts and how such shifts affect Earth’s natural carbon-climate regulation system.

Drawing on geochemical analyses of isotopes in sediments, the research team compared the data with a specially designed model, which included a representation of vegetation and its role in regulating the geological climate system. They used the model to test how the Earth system responds to the intense release of carbon from volcanic activity in different scenarios. They studied three significant climatic shifts in geological history, including the Siberian Traps event that caused the Permian-Triassic mass extinction about 252 million years ago. ETH Zurich professor, Taras Gerya points out, “The Siberian Traps event released some 40,000 gigatons (Gt) of carbon over 200,000 years. The resulting increase in global average temperatures between 5 — 10°C caused Earth’s most severe extinction event in the geologic record.”

Move, adapt, or perish

“The recovery of vegetation from the Siberian Traps event took several millions of years and during this time Earth’s carbon-climate regulation system would have been weak and inefficient resulting in long-term climate warming,” explains lead author, Julian Rogger, ETH Zurich.

Researchers found that the severity of such events is determined by how fast emitted carbon can be returned to Earth’s interior — sequestered through silicate mineral weathering or organic carbon production, removing carbon from Earth’s atmosphere. They also found that the time it takes for the climate to reach a new state of equilibrium depended on how fast vegetation adapted to increasing temperatures. Some species adapted by evolving and others by migrating geographically to cooler regions. However, some geological events were so catastrophic that plant species simply did not have enough time to migrate or adapt to the sustained increase in temperature. The consequences of which left its geochemical mark on climate evolution for thousands, possibly millions, of years.

Today’s human-induced climate crisis

What does this mean for human induced climate change? The study found that a disruption of vegetation increased the duration and severity of climate warming in the geologic past. In some cases, it may have taken millions of years to reach a new stable climatic equilibrium due to a reduced capacity of vegetation to regulate Earth’s carbon cycle.

“Today, we find ourselves in a major global bioclimatic crisis,” comments Loïc Pellissier, Professor of Ecosystems and Landscape Evolution at ETH Zurich and WSL. “Our study demonstrates the role of a functioning of vegetation to recover from abrupt climatic changes. We are currently releasing greenhouse gases at a faster rate than any previous volcanic event. We are also the primary cause of global deforestation, which strongly reduces the ability of natural ecosystems to regulate the climate. This study, in my perspective, serves as ‘wake-up call’ for the global community.”

“Our research has the potential to improve the success of stem-cell transplants and expand their use,” explained Ulrich Steidl, M.D., Ph.D., professor and chair of cell biology, interim director of the Ruth L. and David S. Gottesman Institute for Stem Cell Research and Regenerative Medicine, and the Edward P. Evans Endowed Professor for Myelodysplastic Syndromes at Einstein, and deputy director of the National Cancer Institute-designated Montefiore Einstein Comprehensive Cancer Center (MECCC).

Dr. Steidl, Einstein’s Britta Will, Ph.D., and Xin Gao, Ph.D., a former Einstein postdoctoral fellow, now at the University of Wisconsin in Madison, are co-corresponding authors on the paper.

Mobilizing Stem Cells

Stem-cell transplants treat diseases in which an individual’s hematopoietic (blood-forming) stem cells (HSCs) have become cancerous (as in in leukemia or myelodysplastic syndromes) or too few in number (as in bone marrow failure and severe autoimmune disorders). The therapy involves infusing healthy HSCs obtained from donors into patients. To harvest those HSCs, donors are given a drug that causes HSCs to mobilize, or escape, from their normal homes in the bone marrow and enter the blood, where HSCs can be separated from other blood cells and then transplanted. However, drugs used to mobilize HSCs often don’t liberate enough of them for the transplant to be effective.

“It’s normal for a tiny fraction of HSCs to exit the bone marrow and enter the blood stream, but what controls this mobilization isn’t well understood,” said Dr. Will, associate professor of oncology and of medicine, and the Diane and Arthur B. Belfer Faculty Scholar in Cancer Research at Einstein, and the co-leader of the Stem Cell and Cancer Biology research program at MECCC. “Our research represents a fundamental advance in our understanding, and points to a new way to improve HSC mobilization for clinical use.”

Tracking Trogocytosis

The researchers suspected that variations in proteins on the surface of HSCs might influence their propensity to exit the bone marrow. In studies involving HSCs isolated from mice, they observed that a large subset of HSCs display surface proteins normally associated with macrophages, a type of immune cell. Moreover, HSCs with these surface proteins largely stayed in the bone marrow, while those without the markers readily exited the marrow when drugs for boosting HSCs mobilization were given.

After mixing HSCs with macrophages, the researchers discovered that some HSCs engaged in trogocytosis, a mechanism whereby one cell type extracts membrane fractions of another cell type and incorporates them into their own membranes. Those HSCs expressing high levels of the protein c-Kit on their surface were able to carry out trogocytosis, causing their membranes to be augmented with macrophage proteins — and making them far more likely than other HSCs to stay in the bone marrow. The findings suggest that impairing c-Kit would prevent trogocytosis, leading to more HSCs being mobilized and made available for transplantation.

“Trogocytosis plays a role in regulating immune responses and other cellular systems, but this is the first time anyone has seen stem cells engage in the process. We are still seeking the exact mechanism for how HSCs regulate trogocytosis,” said Dr. Gao, assistant professor of pathology and laboratory medicine at the University of Wisconsin-Madison, Madison, WI.

The researchers intend to continue their investigation into this process: “Our ongoing efforts will look for other functions of trogocytosis in HSCs, including potential roles in blood regeneration, eliminating defective stem cells and in hematologic malignancies,” added Dr. Will.

The study originated in the laboratory of the late Paul S. Frenette, M.D., a pioneer in hematopoietic stem cell research and founding director of the Ruth L. and David S. Gottesman Institute for Stem Cell Biology and Regenerative Medicine Research at Einstein. Other key contributors include Randall S. Carpenter, Ph.D., and Philip E. Boulais, Ph.D., both postdoctoral scientists at Einstein.

The Science paper is titled, “Regulation of the hematopoietic stem cell pool by c-Kit-associated trogocytosis.” Additional authors are Huihui Li, Ph.D., and Maria Maryanovich, Ph.D., both at Einstein, Christopher R. Marlein, Ph.D., at Einstein and FUJIFILM Diosynth Biotechnologies, Wilton, England, and Dachuan Zhang, Ph.D., at Einstein and Shanghai Jiao Tong University School of Medicine, Shanghai, China, Matthew Smith at the University of Wisconsin-Madison, and David J. Chung, M.D., Ph.D., at Memorial Sloan Kettering Cancer Center, New York, NY.

The study was funded by grants from the National Institutes of Health (U01DK116312, R01DK056638, R01DK112976, R01HL069438, DK10513, CA230756, R01HL157948 and R35CA253127).

Researchers found the protein, which they named PKZILLA-1, while studying how a type of algae called Prymnesium parvum makes its toxin, which is responsible for massive fish kills.

“This is the Mount Everest of proteins,” said Bradley Moore, a marine chemist with joint appointments at Scripps Oceanography and Skaggs School of Pharmacy and Pharmaceutical Sciences and senior author of a new study detailing the findings. “This expands our sense of what biology is capable of.”

PKZILLA-1 is 25% larger than titin, the previous record holder, which is found in human muscles and can reach 1 micron in length (0.0001 centimeter or 0.00004 inch).

Published today in Science and funded by the National Institutes of Health and the National Science Foundation, the study shows that this giant protein and another super-sized but not record-breaking protein — PKZILLA-2 — are key to producing prymnesin — the big, complex molecule that is the algae’s toxin. In addition to identifying the massive proteins behind prymnesin, the study also uncovered unusually large genes that provide Prymnesium parvum with the blueprint for making the proteins.

Finding the genes that undergird the production of the prymnesin toxin could improve monitoring efforts for harmful algal blooms from this species by facilitating water testing that looks for the genes rather than the toxins themselves.

“Monitoring for the genes instead of the toxin could allow us to catch blooms before they start instead of only being able to identify them once the toxins are circulating,” said Timothy Fallon, a postdoctoral researcher in Moore’s lab at Scripps and co-first author of the paper.

Discovering the PKZILLA-1 and PKZILLA-2 proteins also lays bare the alga’s elaborate cellular assembly line for building the toxins, which have unique and complex chemical structures. This improved understanding of how these toxins are made could prove useful for scientists trying to synthesize new compounds for medical or industrial applications.

“Understanding how nature has evolved its chemical wizardry gives us as scientific practitioners the ability to apply those insights to creating useful products, whether it’s a new anti-cancer drug or a new fabric,” said Moore.

Prymnesium parvum, commonly known as golden algae, is an aquatic single-celled organism found all over the world in both fresh and saltwater. Blooms of golden algae are associated with fish die offs due to its toxin prymnesin, which damages the gills of fish and other water breathing animals. In 2022, a golden algae bloom killed 500-1,000 tons of fish in the Oder River adjoining Poland and Germany. The microorganism can cause havoc in aquaculture systems in places ranging from Texas to Scandinavia.

Prymnesin belongs to a group of toxins called polyketide polyethers that includes brevetoxin B, a major red tide toxin that regularly impacts Florida, and ciguatoxin, which contaminates reef fish across the South Pacific and Caribbean. These toxins are among the largest and most intricate chemicals in all of biology, and researchers have struggled for decades to figure out exactly how microorganisms produce such large, complex molecules.

Beginning in 2019, Moore, Fallon and Vikram Shende, a postdoctoral researcher in Moore’s lab at Scripps and co-first author of the paper, began trying to figure out how golden algae make their toxin prymnesin on a biochemical and genetic level.

The study authors began by sequencing the golden alga’s genome and looking for the genes involved in producing prymnesin. Traditional methods of searching the genome didn’t yield results, so the team pivoted to alternate methods of genetic sleuthing that were more adept at finding super long genes.

“We were able to locate the genes, and it turned out that to make giant toxic molecules this alga uses giant genes,” said Shende.

With the PKZILLA-1 and PKZILLA-2 genes located, the team needed to investigate what the genes made to tie them to the production of the toxin. Fallon said the team was able to read the genes’ coding regions like sheet music and translate them into the sequence of amino acids that formed the protein.

When the researchers completed this assembly of the PKZILLA proteins they were astonished at their size. The PKZILLA-1 protein tallied a record-breaking mass of 4.7 megadaltons, while PKZILLA-2 was also extremely large at 3.2 megadaltons. Titin, the previous record-holder, can be up to 3.7 megadaltons — about 90-times larger than a typical protein.

After additional tests showed that golden algae actually produce these giant proteins in life, the team sought to find out if the proteins were involved in making the toxin prymnesin. The PKZILLA proteins are technically enzymes, meaning they kick off chemical reactions, and the team played out the lengthy sequence of 239 chemical reactions entailed by the two enzymes with pens and notepads.

“The end result matched perfectly with the structure of prymnesin,” said Shende.

Following the cascade of reactions that golden algae uses to make its toxin revealed previously unknown strategies for making chemicals in nature, said Moore. “The hope is that we can use this knowledge of how nature makes these complex chemicals to open up new chemical possibilities in the lab for the medicines and materials of tomorrow,” he added.

Finding the genes behind the prymnesin toxin could allow for more cost effective monitoring for golden algae blooms. Such monitoring could use tests to detect the PKZILLA genes in the environment akin to the PCR tests that became familiar during the COVID-19 pandemic. Improved monitoring could boost preparedness and allow for more detailed study of the conditions that make blooms more likely to occur.

Fallon said the PKZILLA genes the team discovered are the first genes ever causally linked to the production of any marine toxin in the polyether group that prymnesin is part of.

Next, the researchers hope to apply the non-standard screening techniques they used to find the PKZILLA genes to other species that produce polyether toxins. If they can find the genes behind other polyether toxins, such as ciguatoxin which may affect up to 500,000 people annually, it would open up the same genetic monitoring possibilities for a suite of other toxic algal blooms with significant global impacts.

In addition to Fallon, Moore and Shende from Scripps, David Gonzalez and Igor Wierzbikci of UC San Diego along with Amanda Pendleton, Nathan Watervoort, Robert Auber and Jennifer Wisecaver of Purdue University co-authored the study.

“Previous publications from our lab have mainly focused on neuronal protection,” said Li-Huei Tsai, Picower Professor in The Picower Institute for Learning and Memory and the Department of Brain and Cognitive Sciences at MIT and senior author of the new study in Nature Communications. Tsai also lead’s MIT’s Aging Brain Initiative. “But this study shows that it’s not just the gray matter, but also the white matter that’s protected by this method.”

This year Cognito Therapeutics, the spin-off company that licensed MIT’s sensory stimulation technology, published phase II human trial results in the Journal of Alzheimer’s Disease indicating that 40Hz light and sound stimulation significantly slowed the loss of myelin in volunteers with Alzheimer’s. Also this year Tsai’s lab published a study showing that gamma sensory stimulation helped mice withstand neurological effects of chemotherapy medicines, including by preserving myelin. In the new study, members of Tsai’s lab led by former postdoc Daniela Rodrigues Amorim used a common mouse model of myelin loss — a diet with the chemical cuprizone — to explore how sensory stimulation preserves myelination.

Amorim and Tsai’s team found that 40Hz light and sound not only preserved myelination in the brains of cuprizone-exposed mice, it also appeared to protect oligodendrocytes (the cells that myelinate neural axons), sustain the electrical performance of neurons, and preserve a key marker of axon structural integrity. When the team looked into the molecular underpinnings of these benefits, they found clear signs of specific mechanisms including preservation of neural circuit connections called synapses; a reduction in a cause of oligodendrocyte death called “ferroptosis;” reduced inflammation; and an increase in the ability of microglia brain cells to clean up myelin damage so that new myelin could be restored.

“Gamma stimulation promotes a healthy environment,” said Amorim who is now a Marie Curie Fellow at the University of Galway in Ireland. “There are several ways we are seeing different effects.”

The findings suggest that gamma sensory stimulation may help not only Alzheimer’s disease patients but also people battling other diseases involving myelin loss, such as multiple sclerosis, the authors wrote in the study.

Maintaining myelin

To conduct the study, Tsai and Amorim’s team fed some male mice a diet with cuprizone and gave other male mice a normal diet for six weeks. Halfway into that period, when cuprizone is known to begin causing its most acute effects on myelination, they exposed some mice from each group to gamma sensory stimulation for the remaining three weeks. In this way they had four groups: completely unaffected mice, mice that received no cuprizone but did get gamma stimulation, mice that received cuprizone and constant (but not 40Hz) light and sound as a control, and mice that received cuprizone and also gamma stimulation.

After the six weeks elapsed, the scientists measured signs of myelination throughout the brains of the mice in each group. Mice that weren’t fed cuprizone maintained healthy levels, as expected. Mice that were fed cuprizone and didn’t receive 40Hz gamma sensory stimulation showed drastic levels of myelin loss. Cuprizone-fed mice that received 40Hz stimulation retained significantly more myelin, rivaling the health of mice never fed cuprizone by some, but not all, measures.

The researchers also looked at numbers of oligodendrocytes to see if they survived better with sensory stimulation. Several measures revealed that in mice fed cuprizone, oligodendrocytes in the corpus callosum region of the brain (a key point for the transit of neural signals because it connects the brain’s hemispheres) were markedly reduced. But in mice fed cuprizone and also treated with gamma stimulation, the number of cells were much closer to healthy levels.

Electrophysiological tests among neural axons in the corpus callosum showed that gamma sensory stimulation was associated with improved electrical performance in cuprizone-fed mice who received gamma stimulation compared to cuprizone-fed mice left untreated by 40Hz stimulation. And when researchers looked in the anterior cingulate cortex region of the brain, they saw that MAP2, a protein that signals the structural integrity of axons, was much better preserved in mice that received cuprizone and gamma stimulation compared to cuprizone-fed mice who did not.

Molecular mechanisms

A key goal of the study was to identify possible ways in which 40Hz sensory stimulation may protect myelin.

To find out, the researchers conducted a sweeping assessment of protein expression in each mouse group and identified which proteins were differentially expressed based on cuprizone diet and exposure to gamma frequency stimulation. The analysis revealed distinct sets of effects between the cuprizone mice exposed to control stimulation and cuprizone-plus-gamma mice.

A highlight of one set of effects was the increase in MAP2 in gamma-treated cuprizone-fed mice. A highlight of another set was that cuprizone mice who received control stimulation showed a substantial deficit in expression of proteins associated with synapses. The gamma-treated cuprizone-fed mice did not show any significant loss, mirroring results in a 2019 Alzheimer’s 40Hz study that showed synaptic preservation. This result is important, the researchers wrote, because neural circuit activity, which depends on maintaining synapses, is associated with preserving myelin. They confirmed the protein expression results by looking directly at brain tissues.

Another set of protein expression results hinted at another important mechanism: ferroptosis. This phenomenon, in which errant metabolism of iron leads to a lethal buildup of reactive oxygen species in cells, is a known problem for oligodendrocytes in the cuprizone mouse model. Among the signs was an increase in cuprizone-fed, control stimulation mice in expression of the protein HMGB1, which is a marker of ferroptosis-associated damage that triggers an inflammatory response. Gamma stimulation, however, reduced levels of HMGB1.

Looking more deeply at the cellular and molecular response to cuprizone demyelination and the effects of gamma stimulation, the team assessed gene expression using single-cell RNA sequencing technology. They found that astrocytes and microglia became very inflammatory in cuprizone-control mice but gamma stimulation calmed that response. Fewer cells became inflammatory and direct observations of tissue showed that microglia became more proficient at clearing away myelin debris, a key step in effecting repairs.

The team also learned more about how oligodendrocytes in cuprizone-fed mice exposed to 40Hz sensory stimulation managed to survive better. Expression of protective proteins such as HSP70 increased and as did expression of GPX4, a master regulator of processes that constrain ferroptosis.

In addition to Amorim and Tsai, the paper’s other authors are Lorenzo Bozzelli, TaeHyun Kim, Liwang Liu, Oliver Gibson, Cheng-Yi Yang, Mitch Murdock, Fabiola Galiana-Meléndez, Brooke Schatz, Alexis Davison, Md Rezaul Islam, Dong Shin Park, Ravikiran M. Raju, Fatema Abdurrob, Alissa J. Nelson, Jian Min Ren, Vicky Yang and Matthew P. Stokes.

Fundacion Bancaria la Caixa, The JPB Foundation, The Picower Institute for Learning and Memory, the Carol and Gene Ludwig Family Foundation, Lester A. Gimpelson, Eduardo Eurnekian, The Dolby Family, Kathy and Miguel Octavio, the Marc Haas Foundation, Ben Lenail and Laurie Yoler, and the National Institutes of Health provided funding for the study.

“I ignored it for years because I thought ‘I am a limnologist, methane is in lakes,'” she said.

But when a local reporter contacted Walter Anthony, who is a research professor at the Institute of Northern Engineering at University of Alaska Fairbanks, to inspect the waterbed-like ground at a nearby golf course, she started to pay attention. Like others in Fairbanks, they lit “turf bubbles” on fire and confirmed the presence of methane gas.

Then, when Walter Anthony looked at nearby sites, she was shocked that methane wasn’t just coming out of a grassland. “I went through the forest, the birch trees and the spruce trees, and there was methane gas coming out of the ground in large, strong streams,” she said.

“We just had to study that more,” Walter Anthony said.

With funding from the National Science Foundation, she and her colleagues launched a comprehensive survey of dryland ecosystems in Interior and Arctic Alaska to determine whether it was a one-off oddity or unforeseen concern.

Their study, published in the journal Nature Communications this July, reported that upland landscapes were releasing some of the highest methane emissions yet documented among northern terrestrial ecosystems. Even more, the methane consisted of carbon thousands of years older than what researchers had previously seen from upland environments.

“It’s a totally different paradigm from the way anyone thinks about methane,” Walter Anthony said.

Because methane is 25 to 34 times more potent than carbon dioxide, the discovery brings new concerns to the potential for permafrost thaw to accelerate global climate change.

The findings challenge current climate models, which predict that these environments will be an insignificant source of methane or even a sink as the Arctic warms.

Typically, methane emissions are associated with wetlands, where low oxygen levels in water-saturated soils favor microbes that produce the gas. Yet methane emissions at the study’s well-drained, drier sites were in some cases higher than those measured in wetlands.

This was especially true for winter emissions, which were five times higher at some sites than emissions from northern wetlands.

Digging into the source

“I needed to prove to myself and everyone else that this is not a golf course thing,” Walter Anthony said.

She and colleagues identified 25 additional sites across Alaska’s dry upland forests, grasslands and tundra and measured methane flux at over 1,200 locations year-round across three years. The sites encompassed areas with high silt and ice content in their soils and signs of permafrost thaw known as thermokarst mounds, where thawing ground ice causes some parts of the land to sink. This leaves behind an “egg carton” like pattern of conical hills and sunken trenches.

The researchers found all but three sites were emitting methane.

The research team, which included scientists at UAF’s Institute of Arctic Biology and the Geophysical Institute, combined flux measurements with an array of research techniques, including radiocarbon dating, geophysical measurements, microbial genetics and directly drilling into soils.

They found that unique formations known as taliks, where deep, expansive pockets of buried soil remain unfrozen year-round, were likely responsible for the elevated methane releases.

These warm winter havens allow soil microbes to stay active, decomposing and respiring carbon during a season that they normally wouldn’t be contributing to carbon emissions.

Walter Anthony said that upland taliks have been an emerging concern for scientists because of their potential to increase permafrost carbon emissions. “But everyone’s been thinking about the associated carbon dioxide release, not methane,” she said.

The research team emphasized that methane emissions are especially high for sites with Pleistocene-era Yedoma deposits. These soils contain large stocks of carbon that extend tens of meters below the ground surface. Walter Anthony suspects that their high silt content prevents oxygen from reaching deeply thawed soils in taliks, which in turn favors microbes that produce methane.

Walter Anthony said it’s these carbon-rich deposits that make their new discovery a global concern. Even though Yedoma soils only cover 3% of the permafrost region, they contain over 25% of the total carbon stored in northern permafrost soils.

The study also found through remote sensing and numerical modeling that thermokarst mounds are developing across the pan-Arctic Yedoma domain. Their taliks are projected to be formed extensively by the 22nd century with continued Arctic warming.

“Everywhere you have upland Yedoma that forms a talik, we can expect a strong source of methane, especially in the winter,” Walter Anthony said.

“It means the permafrost carbon feedback is going to be a lot bigger this century than anybody thought,” she said.

The study, published in the journal Physiology & Behavior, shows that cutting calories by 20% did not significantly reduce the distance that mice voluntarily chose to run each day.

The researchers set out to understand what happens to mice when the amount of food available to them is reduced. The findings, they hoped, would be relevant to wild animals that do not always get as much food as they want on a given day, and also to humans, whose doctors often prescribe dieting.

It is somewhat difficult to obtain accurate data on the amount of voluntary exercise that humans engage in. Though it is easy to categorize what people recognize as voluntary exercise, like a trip to the gym, there is much gray area that’s hard to quantify, such as walking to a cafeteria to purchase lunch instead of eating a meal from a nearby lunch box.

Tracking what lab mice choose to do is much easier, and lab mice generally like to run on wheels for many hours per day. In this study, researchers saw the mice chose to run at similar levels, regardless of how much they ate.

“Voluntary exercise was remarkably resistant to reducing the amount of food by 20% and even by 40%,” said UCR biologist and corresponding study author Theodore Garland, Jr. “They just kept running.”

The researchers spent three weeks getting a baseline level of running activity for the mice, then a week with calories reduced by 20%, and another week at minus 40%. This experiment was done both with regular mice as well as “high runner” mice bred to enjoy running.

Though the high runners reduced their total distance slightly with 40% calorie restriction, the distance was only an 11% reduction. As they started out running three times farther per day than normal mice, the reduction is considered slight. “They’re still running at extremely high levels,” Garland said. The regular mice did not reduce their daily distance, even at 40% calorie reduction.

Because running gives a “runners high,” in part by increasing dopamine and cannabinoid levels in the brain, the researchers believe the mice were motivated to keep going even with less food. “Wheel running is a self-rewarding behavior,” Garland said.

In addition, the researchers were surprised to find that body mass was not significantly affected by the 20% reduction in calories in either the regular or high-runner mice. Although there was some drop in body mass with a 40% reduction, it was not as high as predicted.

“People often lose about 4% of their body mass when they’re dieting. That’s in the same range as these mice,” Garland said.

This study contributes to our understanding of why some people like to exercise and others don’t. In the future, the researchers are planning additional studies to understand why both the amount of voluntary exercise and body mass are so resistant to calorie restriction.

“There has to be some type of compensation going on if your food goes down by 40% and your weight doesn’t go down very much,” Garland said. “Maybe that’s reducing other types of activities, or becoming metabolically more efficient, which we didn’t yet measure.”

As habitat destruction causes food shortages for wild animals, this type of information could be instrumental for people trying to preserve species. And for the many people interested in improving their health, the implications could be similarly significant.

“We don’t want people on diets to say, ‘I don’t have enough energy, so I’ll make up for it by not exercising.’ That would be counterproductive, and now we know, it doesn’t have to be this way,” Garland said.