Scientists at the leading American research center, City of Hope, have revealed a crucial biological mechanism that explains why excess fat tends to accumulate in the abdominal area as people age. This groundbreaking study, published in the journal Science, demonstrated that the aging process activates specialized stem cells, which drastically enhance the body’s capacity to generate new visceral and abdominal fat tissues. Remarkably, this process is often completely independent of a person’s daily diet or level of physical activity.
For a long time, the medical community believed that age-related weight gain and the accumulation of belly fat were primarily driven by a natural slowing of metabolism, physical inactivity, and hormonal imbalances. However, this new discovery has completely reshaped that perspective, establishing that entering mature adulthood awakens an entire army of previously inactive cells that deliberately begin to generate new fat cells. In a younger organism, these adipose progenitor cells, referred to by scientists as APCs, remain mostly dormant and generate new fat tissue only under conditions of extreme necessity. Upon reaching middle age, however, these cells suddenly become active and begin to proliferate intensively, which ultimately manifests as visceral fat around the abdominal organs.
During in-depth studies conducted on laboratory mice, using single-cell RNA sequencing methods, scientists discovered a completely new, previously unknown cellular population. These cells were named age-associated preadipocytes, or CP-As for short. These cells do not exist in younger organisms at all and appear only with the onset of the aging process. As part of the research, a unique cell transplantation experiment was carried out, where scientists took adipose progenitor cells from an aged organism and transplanted them into a young one. The results were astonishing: despite being placed in a youthful environment, the aged cells continued to produce new belly fat at an immense speed. This directly proves that the aggressive fat-formation program is hardcoded into the aging cells themselves and does not depend solely on external environmental factors.
To understand what drives this cellular transformation, the researchers began studying the biological signals that prompt these cells to activate. They discovered a specific signaling pathway in which a key role is played by the leukemia inhibitory factor receptor, or the LIFR protein. It is this precise molecular mechanism that commands CP-A cells to transform into mature fat cells and expand the volume of visceral fat. Through genetic and pharmacological manipulations, the scientists were able to block this signaling pathway under laboratory conditions, resulting in a sharp decline in the rate of abdominal fat formation. This discovery is of paramount importance because it provides a specific biological target for developing future medications that can intentionally block the progression of age-related obesity.
The most promising part of the study involves the analysis of human tissues, as City of Hope scientists examined samples of visceral adipose tissue taken from individuals of various ages. It turned out that exactly the same type of CP-A cells is present in large quantities in the bodies of middle-aged humans as well. In laboratory settings, these human cells also demonstrated an amazing ability to generate new fat cells, confirming that the biological patterns discovered in mice apply fully to humans.
Visceral fat that accumulates in the abdominal cavity is far more dangerous to health than subcutaneous fat, as it is closely linked to increased risks of developing type 2 diabetes, cardiovascular diseases, metabolic syndrome, and certain types of cancer. Therefore, the discovery of these cells is a prerequisite not only for weight control but also for ensuring longevity and healthy aging. The research team is already planning the next phase of their work, which involves developing therapeutic agents capable of selectively eliminating CP-A cells from the organism or completely blocking their signaling system to prevent age-related obesity and its associated severe companion diseases.
