Many people notice a familiar change as they age: the waist gradually expands, even when overall body weight does not change dramatically. This increase in abdominal fat is more than an aesthetic concern. Excess belly fat has been linked to a slower metabolism, accelerated aging, type 2 diabetes, heart disease, and other chronic health problems.
Scientists have long known that body composition changes with age, but it’s unclear exactly why fat tends to accumulate around the midsection.
Now, City of Hope researchers have identified what may be a key biological driver of age-related abdominal fat. Their findings, published in the journal Sciencepoint to a newly identified type of stem cell that appears during aging and may help boost the production of new fat cells. The discovery could eventually lead to new strategies to reduce belly fat and promote healthier aging.
“People often lose muscle and gain body fat as they age, even when their body weight remains the same,” said Qiong (Annabel) Wang, Ph.D., co-corresponding author of the study and associate professor of molecular and cellular endocrinology at City of Hope’s Arthur Riggs Diabetes and Metabolism Research Institute, a leading center for diabetes research. “We found that aging triggers the arrival of a new type of adult stem cells and enhances the mass production of new fat cells in the body, especially around the abdomen.”
Looking beyond enlarged fat cells
The research team worked with scientists at UCLA and conducted a series of experiments in mice that were later supported by studies in human cells.
His research focused on white adipose tissue (WAT), the body’s primary fat storage tissue. White adipose tissue is responsible for storing excess energy and is a major contributor to weight gain and abdominal fat accumulation.
Scientists have long known that existing fat cells can grow as people age. However, researchers suspected that another process could also be contributing to waist expansion: the creation of entirely new fat cells.
If true, that would mean that aged adipose tissue could continue to grow not only by enlarging existing cells, but by constantly adding new ones.
To test this idea, the team studied adipocyte progenitor cells (APCs), a type of stem cell found within adipose tissue. These cells serve as precursors that can mature into fully developed fat cells.
Older stem cells produced much more fat
The researchers transplanted APCs from young and old mice into a separate group of young mice.
The results were surprising. APCs taken from older animals generated a large number of new fat cells.
The opposite experiment produced a very different result. When APCs from young mice were transplanted into older mice, they generated relatively few new fat cells.
This suggested that the ability to aggressively produce fat was built into the older APCs themselves and was not dependent on the age of the animal receiving them.
To understand what was happening at a molecular level, the researchers used single-cell RNA sequencing, a technique that allows scientists to examine gene activity in individual cells.
The analysis revealed that APCs were relatively silent in young mice. However, in middle-aged mice, these cells became very active and began to produce large numbers of new fat cells.
“While the ability of most adult stem cells to grow declines with age, the opposite is true for APCs: Aging unlocks the power of these cells to evolve and propagate,” said Adolfo García-Ocana, Ph.D., Ruth B. & Robert K. Lanman Chair in Genetic Regulation and Drug Discovery Research and chair of the Department of Molecular and Cellular Endocrinology at City of Hope. “This is the first evidence that our belly expands with age due to high production of new fat cells from APCs.”
Discovery of a stem cell related to the new era
The scientists discovered that aging did more than simply activate APCs.
As the mice reached middle age, some APCs transformed into a newly identified stem cell population called committed, age-specific preadipocytes (CP-A).
These cells specifically appeared during aging and proved especially effective at producing new fat cells. Their appearance may help explain why older mice gained more fat as they aged.
The researchers then looked for the biological signals that control this process.
They identified an important signaling pathway known as the leukemia inhibitory factor receptor (LIFR). Signaling pathways are communication systems that allow cells to receive instructions and coordinate their behavior. In this case, LIFR seemed to play an important role in helping CP-A cells multiply and become fat cells.
“We found that the body’s fat production process is driven by LIFR. While young mice do not need this signal to produce fat, older mice do,” Wang explained. “Our research indicates that LIFR plays a crucial role in activating CP-A to create new fat cells and expand abdominal fat in older mice.”
Similar fat-producing cells found in humans
To determine whether the findings could be applied beyond mice, the team analyzed human tissue samples from people of different ages using the same single-cell RNA sequencing method.
The researchers identified cells that closely resembled the newly discovered CP-A. These cells were found in greater quantities in tissues of middle-aged individuals.
Human CP-A also showed a strong ability to generate new fat cells, suggesting that a similar biological process may occur in people.
“Our findings highlight the importance of controlling the formation of new fat cells to address age-related obesity,” Wang said. “Understanding the role of CP-As in metabolic disorders and how these cells emerge during aging could lead to new medical solutions to reduce abdominal fat and improve health and longevity.”
A potential new target for age-related obesity
Although more research is needed, the discovery provides scientists with a promising new target for future therapies.
The researchers now plan to track CP-A cells in animal studies, investigate how these cells behave in humans, and explore ways to block or eliminate them. If successful, these approaches could help prevent the accumulation of abdominal fat that commonly accompanies aging.
The first authors of the study were City of Hope researcher Guan Wang, Ph.D., and UCLA researcher Gaoyan Li, Ph.D.