New research from City of Hope identifies key cellular drivers of age-related abdominal fat, which elucidates why waist circumference tends to expand during middle age and provides promising targets for future therapies to slow aging and prevent chronic diseases.
The study was published today sciencereveals that aging activates a novel adult stem cell that can significantly increase fat production around the abdomen, a process that leads to not only cosmetic changes but also to an increased risk of diabetes, heart disease and metabolic diseases.
“People usually lose muscle and increase body fat as they age, even if their weight remains the same,” said Dr. Qiong (Annabel) Wang, a corresponding author and associate professor at the Hope City of Hope Arthur Riggs Institute for Diabetes and Metabolism. “We found that aging triggered the arrival of a new type of adult stem cells and enhanced the body’s mass production of new fat cells, especially around the abdomen.”
The researchers collaborated with Dr. Xia Yang to conduct a series of experiments on mice and later confirmed samples of human cells, focusing on white adipose tissue (WAT), the main type of fat responsible for middle-aged weight gain. The team studied adipocyte progenitor cells (APCs), stem cells that develop into adipocytes in WAT. By transplanting APCs from young mice and older recipients to younger recipients, scientists observed that older APCs quickly generated a large number of new adipocytes, independent of the age of the host. In contrast, young APCs transplanted to mice were unable to produce obvious new adipose tissue.
“This is the first evidence that our abdomen expands with age due to the high output of new adipocytes from APCs,” said Adolfo Garcia-Ocana, Ph.D., co-author of the Department of Molecular and Cell Endocrinology and chair of the Department of Cell Endocrinology in Hope City. “Although most adult stem cells grow with age, the APC’s ability to develop and spread is exactly the opposite – releasing the ability of these cells to develop and spread.”
The study further suggests that aging converts APC into a new, effective subtype called the promised preadipocyte, age-specific (CP-AS), which emerges in middle age and actively drives adipocyte formation. A signaling pathway called leukemia inhibitor receptor (LIFR) is considered critical to this process, thereby promoting CP-A cell development and fat production.
“We found that the body’s fat production process is driven by LIFR. And young mice don’t need this signal to make fat, and mice do it,” Wang explained. “Our research shows that LIFR plays a crucial role in triggering CP-AS to create new adipocytes and expanding the abdominal fat in mice.”
When the team used single-cell RNA sequencing to study APCs in human tissue samples of all ages, they found that CP-A cells were also present in humans and showed an increased ability to form adipocytes in middle-aged individuals.
“Our findings emphasize the importance of controlling new adipose formation to address age-related obesity,” Wang said. “Understanding the role of CP-AS in metabolic diseases and how these cells emerge during aging may lead to new medical solutions to reduce abdominal fat and improve health and longevity.”
The study was led by Hope City first author Dr Guan Wang and Dr Gaoyan Li of UCLA. Future research will focus on tracking CP-A cells in living organisms and designing treatments to prevent or eliminate these cells, which may inhibit middle-grade weight gain and associated health risks.
