New research from City of Hope has identified a key cellular driver of age-related belly fat, shedding light on why waistlines tend to expand during middle age and offering a promising target for future therapies aimed at slowing aging and preventing chronic diseases.
The study, published today in Science, reveals that aging activates a new type of adult stem cell that significantly increases fat production around the abdomen, a process that contributes not only to cosmetic changes but also to heightened risks for diabetes, heart disease, and metabolic disorders.
“People often lose muscle and gain body fat as they age, even when their body weight remains the same,” said Dr. Qiong (Annabel) Wang, co-corresponding author and associate professor at City of Hope’s Arthur Riggs Diabetes & Metabolism Research Institute. “We discovered aging triggers the arrival of a new type of adult stem cell and enhances the body’s massive production of new fat cells, especially around the belly.”
Working in collaboration with UCLA scientist Dr. Xia Yang, the researchers conducted a series of experiments on mice, later confirmed with human cell samples, focusing on white adipose tissue (WAT)—the primary type of fat responsible for midlife weight gain. The team investigated adipocyte progenitor cells (APCs), stem cells within WAT that develop into fat cells. By transplanting APCs from young and older mice into young recipients, the scientists observed that older APCs rapidly produced vast amounts of new fat cells, independent of the host’s age. Conversely, young APCs transplanted into older mice failed to generate significant new fat tissue.
“This is the first evidence that our bellies expand with age due to the APCs’ high output of new fat cells,” said Dr. Adolfo Garcia-Ocana, co-author and chair of the Department of Molecular & Cellular Endocrinology at City of Hope. “While most adult stem cells’ capacity to grow wanes with age, the opposite holds true with APCs—aging unlocks these cells’ power to evolve and spread.”
The research further showed that aging transforms APCs into a new, potent subtype known as committed preadipocytes, age-specific (CP-As), which emerge in middle age and actively drive fat cell formation. A signaling pathway called leukemia inhibitory factor receptor (LIFR) was identified as essential to this process, promoting CP-A cell development and fat production.
“We discovered that the body’s fat-making process is driven by LIFR. While young mice don’t require this signal to make fat, older mice do,” Wang explained. “Our research indicates that LIFR plays a crucial role in triggering CP-As to create new fat cells and expand belly fat in older mice.”
When the team studied APCs from human tissue samples of various ages using single-cell RNA sequencing, they found that CP-A cells were also present in humans and showed an increased ability to form fat cells in middle-aged individuals.
“Our findings highlight the importance of controlling new fat-cell formation 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 for reducing belly fat and improving health and longevity.”
The research was led by first authors Dr. Guan Wang from City of Hope and Dr. Gaoyan Li from UCLA. Future studies will focus on tracking CP-A cells in living organisms and designing treatments to block or eliminate these cells, potentially curbing midlife weight gain and associated health risks.
