Many adults notice their waistlines expanding during middle age, even without major changes in diet or physical activity. While this shift has long been attributed to slowing metabolism or hormonal changes, new research reveals that a unique population of stem cells in fat tissue emerges with age and actively drives the accumulation of abdominal fat.

A study published in Science by Wang and colleagues provides a detailed look at how adipose progenitor cells (APCs)—the precursors to fat cells—change function in middle age, especially in males. Using advanced lineage tracing and single-cell RNA sequencing in mice, the researchers discovered that, unlike most adult stem cells which lose function with age, a distinct group of APCs called committed preadipocytes, age-enriched (CP-As), actually become more active and proliferative as animals age.

A surge in new fat cells

The research team observed that male mice at 12 months of age—a stage equivalent to human middle age—experienced a dramatic increase in visceral adipose tissue, the type of fat stored deep in the abdomen. More than 80% of the fat cells in this tissue were newly generated, not simply enlarged. This burst of fat cell production was traced to the emergence of CP-A cells, which showed high rates of proliferation and differentiation both in laboratory experiments and when transplanted into young mice.

Further analysis identified the leukemia inhibitory factor receptor (LIFR) as a key signaling molecule that enables CP-A cells to generate new fat cells. Blocking LIFR in mice prevented the expansion of visceral fat and suggests a potential therapeutic target for age-related obesity.

What this means for humans

Importantly, the researchers found similar CP-A cells in human tissue samples, confirming that this process is not limited to mice. The findings help explain why middle-aged adults, particularly men, are prone to accumulating belly fat and developing related metabolic disorders such as insulin resistance and type 2 diabetes.

“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,” said Qiong (Annabel) Wang, Ph.D., cocorresponding author of the study, as quoted in the City of Hope press release.

Looking ahead

These results are supported by additional research from City of Hope and UCLA, as well as coverage in ScienceDaily, all of which highlight the unique, age-specific increase in fat cell formation driven by stem cell changes. The studies collectively suggest that targeting the CP-A population or the LIFR pathway may offer new avenues to combat abdominal obesity and its health risks in aging populations.

Full disclosures for each study can be found in the original publications.

Sources:

• Wang G, Li G, Song A, et al. Distinct adipose progenitor cells emerging with age drive active adipogenesis. Science. 2025;388(6745): DOI: 10.1126/science.adj0430
• City of Hope press release
• ScienceDaily summary