A gradual expansion of the waistline, often decoupleddecoupled/diːˈkʌpəld/L3分离的，脱钩的；指两个原本关联的事物不再相互依赖或同步变化separated or disconnected; no longer linked or dependent on each other from significant overall weight gain, constitutes a familiar and physiologically consequential hallmark of human aging; excess abdominal adiposityadiposity/ˌædɪˈpɒsɪti/L3肥胖，脂肪过多；特指身体脂肪组织的过度积累the state of being excessively fat or having an abundance of adipose tissue is unequivocally linked to metabolic dysregulation, accelerated biological aging, type 2 diabetes, and cardiovascular pathology. Notwithstanding decades of observation, the precise molecular mechanisms driving this preferential accumulation of visceral fat have remained obstinately elusiveelusive/ɪˈluːsɪv/L3难以捉摸的，难以理解的；指难以发现、描述或实现的事物difficult to find, catch, or achieve; hard to define or describe. Researchers at City of Hope, whose findings were published in Science, have now identified a novel biological driver: a previously uncharacterized population of stem cells that emerges specifically during aging and appears to orchestrate a surge in de novo adipogenesis, particularly within the abdominal depot. This discovery, which augments our understanding of age-related body composition changes, may ultimately furnish a promising therapeutic target for mitigating middle-age obesity and promoting healthier aging trajectories.
The investigation, a collaborative effort with UCLA, employed a series of murine experiments subsequently corroboratedcorroborated/kəˈrɒbəreɪtɪd/L3证实，确证；通过提供证据或信息来支持或确认某一说法confirmed or supported with evidence or additional information by analyses of human tissue. The team focused on white adipose tissue (WAT), the body's principal energy reservoir and the primary locus of pathological fat accumulation. While it has long been known that existing adipocytes can hypertrophy with age, the researchers hypothesized that an additional, parallel process—the generation of entirely new fat cells from progenitor populations—might be contributing to the expanding girth. To test this, they examined adipocyte progenitor cells (APCs), a class of stem cell resident within fat tissue that can differentiate into mature adipocytes.
Strikingly, when APCs from aged mice were transplanted into young recipients, they generated a profusion of new fat cells; conversely, APCs from young donors produced relatively few when placed into older hosts. This indicated that the capacity for aggressive adipogenesis was intrinsicintrinsic/ɪnˈtrɪnsɪk/L3内在的，固有的；属于事物本质的，非外部赋予的belonging naturally to something; inherent rather than derived from external sources to the aged APCs themselves, independent of the systemic milieu. Single-cell RNA sequencing revealed that APCs were quiescent in young mice but became highly active in middle-aged animals. Furthermore, aging triggered the transformation of some APCs into a distinct, previously undocumented cell type—committed preadipocytes, age-specific (CP-As)—which proved exceptionally efficient at generating adipocytes. Their emergence was governed by the leukemia inhibitory factor receptor (LIFR) signaling pathway, a communication system that, crucially, was required for fat production in older mice but dispensable in younger ones.
To ascertain translational relevance, the researchers applied the same single-cell sequencing methodology to human tissue samples across a spectrum of ages. They identified cells bearing a striking resemblance to the murine CP-As, which were more abundant in middle-aged individuals and exhibited a pronounced capacity for adipogenesis. This suggests that a homologous biological process likely operates in humans, underpinning the characteristic accumulation of belly fat with age. Consequently, CP-As and the LIFR signaling axis represent promising targets for pharmacological intervention. Future research will focus on tracking these cells in animal models, elucidating their behavior in human subjects, and exploring strategies to block or eliminate them, potentially forestalling the metabolic consequences of age-related obesity.
