Rutgers Health researchers have made discoveries about brown fat that may open a new path to helping people stay physically fit as they age.
A team from Rutgers New Jersey Medical School found that mice lacking a specific gene developed an unusually potent form of brown fat tissue that expanded lifespan and increased exercise capacity by roughly 30%. The team is working on a drug that could mimic these effects in humans.
"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 Aging Cell. "This mouse model performs exercise better than their normal littermates."
Unlike white fat, which stores energy, brown fat burns calories and helps regulate body temperature. This study revealed brown fat also plays a crucial role in exercise capacity by improving blood flow to muscles 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.
The discovery emerged from broader research into healthy aging. The modified mice, which lack a protein called RGS14, live about 20% longer than normal mice, with females living longer than males – similar to the pattern seen in humans. Even at advanced ages, they maintain a healthier appearance, avoiding the typical signs of aging, such as loss of hair and graying that appear in normal elderly mice. Their brown adipose tissue also protects them from obesity, glucose intolerance, cardiovascular disorders, cancer and Alzheimer's disease, in addition to reduced exercise tolerance.
To test whether the brown fat – rather than some other result from the missing genes –accounted for the benefits, the researchers transplanted the brown fat to normal mice. They noted that the recipients gained similar benefits within days. Transplants using regular brown fat from normal mice, by contrast, took eight weeks to produce much milder improvements.
The discovery could eventually improve human lifespans – the total time when people enjoy good mental and physical health.
"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."
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.
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.
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.
