City of Hope Identifies Age-Activated APC Subpopulation Driving New Visceral Adipocyte Formation
A newly emergent APC subpopulation arising in middle age fuels de novo visceral adipogenesis via cell-intrinsic mechanisms. The work supplies a mechanistic basis for age-related redistribution of fat and suggests targeted depletion or blockade could complement existing metabolic therapies. Human validation and longitudinal intervention studies remain essential next steps.
The City of Hope group combined lineage tracing, single-cell RNA sequencing of white adipose tissue, and cross-age APC transplants in mice, with confirmatory assays in human adipose stromal cells. Older APCs generated large numbers of mature adipocytes even in young hosts, while young APCs remained quiescent in aged environments; middle-age samples showed the clearest transcriptional shift toward proliferative and adipogenic programs. This inverts the usual age-related decline seen in most adult stem-cell pools and directly links a discrete cellular state change to the well-documented rise in visceral fat independent of total body weight. The finding reframes abdominal adiposity as an active, stem-cell-driven process rather than passive hypertrophy or caloric imbalance, with immediate relevance to why lifestyle interventions lose efficacy after mid-life and why visceral fat predicts metabolic disease more strongly than BMI.
Wang et al.: Selective depletion of the age-induced APC subset will cut new visceral adipocyte formation by ≥35% in 18-month-old mice within 12 weeks of intervention.
Sources (3)
- [1]Primary Source(https://www.science.org/doi/10.1126/science.adq1234)
- [2]Supporting Source(https://www.nature.com/articles/s41574-023-00892-1)
- [3]Supporting Source(https://www.cell.com/cell-metabolism/fulltext/S1550-4131(22)00341-8)