In a world where on-off switches are ubiquitous, it’s easy to see why such a switch could be so appealing, biologically speaking. Turn on what you want. Turn off what you don’t.
In August 2020, an international research team reported that it had discovered how to activate something called brown fat. Brown fat is one of the keys to metabolism, controlling obesity and diabetes, and perhaps longevity. The results of the collaboration between the Centre de recherche du Centre hospitalier universitaire de Sherbrooke (CRCHUS) in Québec and the Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR) at the University of Copenhagen were published in the journal Cell Metabolism.
Brown fat burns energy and generates heat—a process called thermogenesis—after being activated by cold temperatures or chemical signals. Humans have small deposits of brown fat, and scientists have long hypothesized that finding alternative ways to pharmacologically activate that fat or turn white fat into brown fat could help improve metabolism.
White vs brown fat
Not all fat is created equal. The fat most people picture is known as white fat, since it looks white or white-yellow when you see it under the skin. But you’re also born with brown fat (which, unsurprisingly, looks brown).
Brown fat—found in the neck and shoulders of newborns—is metabolically efficient, in that it burns lots of calories, which serves the purpose of keeping you warm (important for newborns). We lose most our brown fat as we age. By age six, you have less than 5 percent of the brown fat you were born with; the fat we gain over time is almost all white fat. White fat is metabolically inefficient, meaning it’s relatively inactive. It doesn’t use much energy, is hard to burn off, accumulates, and causes other health problems.
But what does this have to do with youthfulness? Well, researchers at a company near UC Davis and separately at the University of Copenhagen have taken white fat in test tubes, regressed it to a more pluripotent fat, flipped a few epigenetic switches, and—voilà!—turned it into brown fat. They then injected the brown fat into fat sheep. What happened? As hoped, the sheep with more brown fat got thin and lost their metabolic syndrome and diabetes.
One roadblock to using brown fat is that all the good stuff that brown fat does has to be programmed into the previously white fat, but that has proved doable. A group in Delaware has done this white to brown fat transformation in a small way by activating dormant brown fat in a few women with an already approved medication. That could lead to research to develop a related but newer medication; it could also lead to a set of stem cell and exosome transplants that can transform more of your white fat to much more metabolically active brown fat. Most older people don’t have significant amounts of brown fat. So you need to do more than just activate the brown fat you have—you need more brown fat.
Reprogramming and regeneration
But what if a person’s white fat could be turned into brown fat, through what is called induced tissue regeneration—using reprogramming to transform one cell type to pluripotent cells? Then what if specific genes could be turned on to make those cells function like brown fat cells? And what if those newly made brown fat cells could then get injected back into the person?
This process requires two distinct and important discoveries. As we noted earlier, induced pluripotent stem cells from adult cells hold great promise. Dr. Shinya Yamanaka in Japan has reverted adult cells to their original embryonic state (at which point they could turn into many different cells such as brown fat, or white fat, or heart or brain or kidney, etc.). Dr. Yamanaka did this reversion by turning on four genes (now called the Yamanaka factors), which he accomplished by activating four embryonic switches.
So, after reverting adult white fat cells into pluripotent cells, the research group then made a few more epigenetic switches to make brown fat cells. They then grew the brown fat cells in culture and made them non-immunogenic by activating another gene that changed the expression of proteins on the cells’ surface. That made it possible to inject the brown fat back into fat sheep without the sheep rejecting it.
The timetable for this game-changing ability to turn white fat to brown fat is predicted to be less than five years away after human studies start. The brown fat will likely make you much thinner, and reduce your risk of diabetes, heart disease, cancer, osteoarthritis, and dementia.
Why is this important? Since 1974, one of the major causes of shortened life spans and of both disease itself and the uptick in chronic illnesses like osteoarthritis, type 2 diabetes, and many cancers is that increasing level of white fat. Many of the symptoms of aging, even fatigue and a lack of energy, are derived from the biological destruction and inflammation that comes from excess white fat. The accumulation of white fat in society has resulted in a life expectancy that is shorter than it would be.
And while medical treatments have mitigated much of the disease and life expectancy change caused by white fat, humans continue to accumulate excess white fat. Much of that increase comes from eating foods that have saturated fats and foods that produce an increase in blood sugar levels too quickly.
If scientists find a way to replace white fat with brown fat it will likely lead to greatly reduced risks of all inflammatory diseases like osteoarthritis, diabetes, heart disease, stroke, and brain dysfunction and provide increased energy levels. That is, you become operationally younger. Bring it on!