Adipocytes. 3d rendered close-up illustration of human fat cells. (Image by Olga Zinkevych on Shutterstock)
Mouse model study shows how brown fat could improve exercise performance and extend one’s lifespan
In a nutshell
- Brown fat, unlike white fat, burns calories and can boost exercise performance by improving blood flow to muscles during physical activity
- Mice with enhanced brown fat lived 20% longer and showed 30% better exercise performance, with the benefits transferable through tissue transplantation
- Rutgers researchers are developing a drug that could activate brown fat in humans, potentially helping people maintain physical fitness as they age
NEW BRUNSWICK, N.J. — The next breakthrough in anti-aging medicine might come from a surprising source: fat. But not just any fat—brown fat, a special type that burns energy rather than storing it. Researchers at Rutgers University are developing a pill that could boost this beneficial tissue’s activity, after discovering its remarkable effects on exercise capacity and lifespan in mice. Their work suggests that activating brown fat could be the key to staying physically fit as we age, with a drug potentially available for testing within a year.
The new research paper published in the journal Aging shows that brown fat isn’t just for keeping us warm—it actively contributes to better exercise performance and potentially extends our healthy years. The paper, authored by Dorothy E. Vatner, Jie Zhang, and Stephen F. Vatner from Rutgers New Jersey Medical School, offers a fresh perspective on fat tissue and its surprising connections to exercise capacity and longevity.
“Exercise capacity diminishes as you get older, and to have a technique that could enhance exercise performance would be very beneficial for healthful aging,” said Stephen Vatner, university professor and director of the Cardiovascular Research Institute in the medical school’s Department of Cell Biology and Molecular Medicine and senior author of the study, in a statement. “This mouse model performs exercise better than their normal littermates.”
Not All Fat Is Created Equal
Most people think of fat as something to lose, but brown fat, (also known as brown adipose tissue) works differently from the white fat we typically try to shed. This special tissue burns calories rather than storing them, generating heat through a process called thermogenesis. While scientists have known about brown fat’s heat-producing abilities for decades, the connection between the tissue and exercise performance represents a fascinating new frontier.
The Rutgers team has been studying a particular genetic model—mice lacking a protein called regulator of G protein signaling 14 (RGS14)—that exhibit dramatically extended lifespans and enhanced exercise performance. Their research found that these long-lived mice have more potent brown fat, which appears to be directly responsible for their impressive physical abilities and longevity.
The color difference between white and brown fat isn’t just cosmetic. Brown fat cells contain numerous mitochondria—cellular power plants that give these cells their distinctive brown color. These mitochondria are packed with a protein called uncoupling protein 1 (UCP1), which allows them to generate heat instead of the usual cellular energy currency, ATP. This metabolic flexibility makes brown fat uniquely positioned to influence whole-body energy expenditure.
Impressive Results From Brown Fat Transplantation
The researchers’ most compelling evidence comes from transplantation experiments. When they transplanted brown fat from the long-lived RGS14 knockout mice into normal mice, the recipients experienced dramatically enhanced exercise performance within just three days. In contrast, normal mice receiving brown fat transplants from other normal mice also showed improvement—but only after eight weeks. This suggests that the brown fat from the long-lived mice possesses unique properties that can rapidly boost exercise capacity.
Scientists say that the transplanted brown fat increased blood flow to the legs during exercise, promoting better oxygen and nutrient delivery to working muscles. It also stimulated the formation of new blood vessels and increased the density of existing ones. In essence, the brown fat was helping to build a more efficient circulatory system for delivering fuel during physical activity.
The genetically modified mice produced unusually high amounts of active brown fat and showed about 30% better exercise performance than normal mice, both in speed and time to exhaustion.
At the molecular level, several pathways appear to be activated by the enhanced brown fat, including SIRT3 (a longevity-associated protein), MEK/ERK signaling, and increased levels of vascular endothelial growth factor (VEGF). These pathways collectively improve mitochondrial function, reduce oxidative stress, and enhance blood flow—all critical factors for exercise performance and potentially for longevity.
Aging Better With Brown Fat
The connection to aging becomes even more apparent when examining the physical appearance of the genetically modified mice. Normal mice show typical signs of aging—graying fur, hair loss, and general body atrophy—but the long-lived RGS14 knockout mice maintain a more youthful appearance well into old age. Even at advanced ages, they maintain a healthier appearance, avoiding the typical signs of aging that appear in normal elderly mice.
The modified mice live about 20% longer than normal mice, with females living longer than males – similar to the pattern seen in humans. While the paper doesn’t explore the gender difference in depth, it raises intriguing questions about sex hormones and their potential interaction with brown adipose tissue function.
The medical applications extend far beyond the gym. If brown fat truly has the protective effects suggested by this research, it could become a therapeutic target for preventing or treating a host of age-related conditions. Obesity, diabetes, cardiovascular disease, cancer, and Alzheimer’s disease are all mentioned as potential conditions that might respond to brown fat-based interventions.
“With all the medical advances, aging and longevity have increased in humans, but unfortunately, healthful aging hasn’t,” Vatner said. “There are a lot of diseases associated with aging – obesity, diabetes, myocardial ischemia, heart failure, cancer – and what we have to do is find new drugs based on models of healthful aging.”
From Lab to Real Life
Rather than develop a treatment that addresses aging broadly, which poses regulatory challenges, Vatner said his team plans to test for specific benefits such as improved exercise capacity and metabolism. This approach builds on their previous success in developing a drug based on a different mouse healthful longevity model.
“We’re working with some people to develop this agent, and hopefully, in another year or so, we’ll have a drug that we can test,” Vatner said. He added that most people would prefer to increase brown fat levels by taking pills rather than ice baths and is optimistic about translating the newest finding into an effective medication.
For those wondering how to activate their own brown fat now, current science suggests that cold exposure is one of the most effective natural stimulants. When we’re cold, the sympathetic nervous system releases norepinephrine, which binds to receptors on brown fat cells and activates UCP1-mediated heat production. In the meantime, techniques such as deliberate cold exposure can increase brown fat naturally. Studies have found such efforts to produce short-term benefits that range from enhanced immune system function to improved metabolic health, but Vatner said none of the studies have run long enough to find any effect on healthful aging.
For now, the path from these mouse studies to human applications remains uncertain, but study authors are hopeful that a brown fat-activating drug is in reach.
Paper Summary
Methodology
The researchers used a genetically modified mouse lacking the regulator of G protein signaling 14 (RGS14 knockout mice), which they compared to normal mice. To determine if brown fat was responsible for the benefits they observed, the team performed transplantation experiments, surgically moving brown fat from RGS14 KO mice into normal mice, then testing the recipients’ exercise performance on specialized treadmills. They measured hind limb blood flow using imaging techniques and examined tissue samples for signs of new blood vessel formation. The team also analyzed molecular markers to identify the specific cellular pathways involved in the effects of brown fat on exercise capacity.
Results and Limitations
The genetically modified mice lived about 20% longer than normal mice and showed approximately 30% better exercise performance. When brown fat from these mice was transplanted into normal mice, the recipients experienced enhanced exercise capacity within just three days, compared to the eight weeks needed for normal mice receiving brown fat from other normal mice. The improved performance came with increased blood flow to the hind limbs and higher density of blood vessels in the muscles.
Despite these promising results, the study has limitations. Mouse models don’t always translate directly to human physiology, and the transplantation approach isn’t directly applicable as a human intervention. The paper also notes inconsistent findings in the field regarding the effects of exercise on brown fat, suggesting complex relationships that may vary based on intensity, duration, and individual factors.
Publication Information
This research perspective titled “Brown adipose tissue enhances exercise performance and healthful longevity” was authored by Dorothy E. Vatner, Jie Zhang, and Stephen F. Vatner from the Department of Cell Biology and Molecular Medicine at Rutgers New Jersey Medical School. The paper was published on December 18, 2024, in the journal Aging. The study was supported by a grant from the National Institutes of Health.
