A groundbreaking study from City of Hope has uncovered a key cellular mechanism behind age-related belly fat, revealing why waistlines tend to expand during middle age and pointing to a promising new target for anti-aging and disease-prevention therapies.
Published in Science, the research shows that aging activates a unique type of adult stem cell that significantly boosts fat production in the abdominal area. This not only leads to visible weight gain but also increases the risk of serious health conditions like type 2 diabetes, heart disease, and other metabolic disorders.
“Many people experience muscle loss and fat gain as they age, even without a change in overall body weight,” said Dr. Qiong (Annabel) Wang, co-corresponding author and associate professor at City of Hope’s Arthur Riggs Diabetes & Metabolism Research Institute. “We found that aging triggers the emergence of a new adult stem cell type that drives belly fat production.”
Collaborating with UCLA’s Dr. Xia Yang, the team conducted detailed experiments using mice and human fat tissue samples. They focused on white adipose tissue (WAT)—the primary fat linked to weight gain in middle age. Researchers examined adipocyte progenitor cells (APCs), stem cells that mature into fat cells.
By transplanting APCs from young and older mice into young recipients, scientists observed that older APCs led to a rapid buildup of abdominal fat, regardless of the host’s age. In contrast, young APCs implanted in older mice didn’t produce significant fat, proving that the aging cells themselves were the main fat producers.
“This is the first clear evidence that APCs drive age-related belly fat,” said Dr. Adolfo Garcia-Ocana, co-author and chair of Molecular & Cellular Endocrinology at City of Hope. “Unlike most adult stem cells that lose function with age, APCs gain power and fat-forming capacity as we get older.”
The study also identified a newly transformed version of these stem cells, called committed preadipocytes, age-specific (CP-As). These cells emerge in middle age and are hyperactive in forming new fat cells. A key player in this process is the leukemia inhibitory factor receptor (LIFR) pathway, which researchers found to be essential in triggering CP-A activity and belly fat buildup.
“LIFR drives the fat-forming process in aging tissue,” Wang noted. “Young mice don’t rely on this pathway, but older mice do. This signal fuels CP-A development and accelerates belly fat growth.”
Using advanced single-cell RNA sequencing, the researchers also confirmed that CP-A cells exist in human fat tissue and are especially active in middle-aged individuals.
“Our findings suggest that targeting CP-As could be a powerful strategy to reduce age-related belly fat and improve overall health,” Wang added. “This research opens new doors for developing therapies to combat obesity, metabolic disease, and the aging process itself.”
Led by Dr. Guan Wang from City of Hope and Dr. Gaoyan Li from UCLA, the next phase of research will focus on tracking CP-A cells in living organisms and exploring treatments that can block or eliminate them—potentially reducing midlife fat gain and its associated health risks.