Researchers at City of Hope report that aging can spur the emergence of an age-enriched population of adipose progenitor cells that is especially prone to generating new fat cells in abdominal white fat. The work, published in Science, points to a signaling pathway that may help drive midlife increases in belly fat and could become a future therapeutic target.
Researchers at City of Hope, working with collaborators at UCLA, examined how white adipose tissue expands with age by studying adipocyte progenitor cells (APCs) in mice and comparing the results with analyses of human tissue.
In transplantation experiments, the team reported that APCs taken from older mice produced large numbers of new fat cells even when transplanted into young animals. By contrast, APCs from young mice produced relatively few new fat cells when transplanted into older recipients—suggesting the heightened fat-forming capacity was largely intrinsic to the older APCs rather than driven only by the recipient’s age.
Using single-cell RNA sequencing, the researchers found that, in middle-aged mice, a subset of APCs shifted into a distinct population the authors call committed preadipocytes, age-specific (CP-As). The study reported that these CP-As were particularly active in proliferating and differentiating into new adipocytes.
The researchers also identified leukemia inhibitory factor receptor (LIFR) signaling as a key pathway associated with this process. Qiong (Annabel) Wang, a co-corresponding author, said the group found that older mice required LIFR signaling to drive fat formation, while young mice did not.
To assess whether a similar phenomenon might occur in people, the team analyzed human adipose tissue samples across ages and reported finding CP-A–like cells in higher numbers in middle-aged individuals.
The authors said the findings suggest that targeting CP-As—or the LIFR-related signaling that supports their fat-forming activity—could eventually inform strategies to limit age-associated abdominal fat. They added that further work is planned to track these cells in animal studies, study their behavior in humans, and explore approaches to block or eliminate them.
