Understanding Middle-Age Waist Expansion: The Role of Aging Stem Cells

As we reach middle age, many notice a gradual increase in abdominal size, a phenomenon that extends beyond mere aesthetics. Belly fat accumulation not only alters body shape but also contributes to accelerated aging and slows metabolic processes, heightening risks for diabetes, cardiovascular diseases, and other chronic conditions. While it has been observed that fat tends to enlarge and multiply with age, the cellular mechanisms driving this process remained unclear.

Recent preclinical studies conducted by City of Hope have shed light on the cellular drivers responsible for age-related abdominal fat build-up. Published in the journal Science, this research uncovers how specific stem cells in adipose tissue are activated during aging, leading to increased fat cell production in the midsection. The findings point toward new potential targets for therapies aimed at reducing belly fat and promoting healthier aging.

Lead researcher Dr. Qiong (Annabel) Wang explained that, unlike muscle tissue which tends to decline with age, certain stem cells in fat tissue become more active, contributing to fat accumulation around the abdomen. The study focused on white adipose tissue (WAT), the primary fat reservoir influencing weight gain. Researchers hypothesized that WAT expands not just by the growth of existing fat cells, but also through the formation of new ones—a process driven by adipocyte progenitor cells (APCs).

In experiments involving mice, transplanted APCs from older animals rapidly generated large quantities of fat cells when introduced into young hosts. Conversely, APCs from young mice transplanted into older hosts did not produce as much fat, indicating that aging intrinsically enhances the fat-producing capacity of these stem cells.

Further analysis using single-cell RNA sequencing revealed that in middle-aged mice, APCs became highly active, signaling an age-dependent awakening that stimulated the creation of new fat cells. A novel cell type, called CP-A (committed preadipocytes, age-specific), was identified as a key player in this process. These cells, emerging during middle age, actively churn out fat cells, explaining the increased belly size typical of aging.

A signaling pathway involving the leukemia inhibitory factor receptor (LIFR) was found to be critical in this process. In older mice, LIFR promoted the proliferation and differentiation of CP-A cells into fat cells. Interestingly, human tissue studies mirrored these findings, showing increased CP-A-like cells in middle-aged individuals, suggesting similar mechanisms are at play in humans.

This research offers promising avenues for future interventions targeting the formation of new fat cells to combat age-related obesity. By understanding how CP-A cells develop and influence fat accumulation, scientists aim to develop strategies to block or eliminate these cells, potentially delaying or preventing belly fat gain and associated health risks.

Future studies will focus on monitoring CP-A cells in human tissues, exploring ways to inhibit their activity, and developing therapies to maintain healthier body composition during aging. This research paves the way for novel approaches to extend health span and reduce the burden of obesity in older populations.