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Abstract
CDKN1A+ senescent cells were identified in 43 normal human livers across various ages and stages of fibrosis.
- Senescent hepatocytes, fibroblasts, cholangiocytes, and endothelial cells were associated with age, liver disease, or cancer.
- Differences in senescence patterns were observed between aged and fibrotic livers, consistent with findings in mouse models.
- CDKN1A+ hepatocytes were found to localize periportally, while SERPINE1+ hepatocytes formed spatial clusters associated with aging.
- CXCL12+ senescent fibroblasts were located in fibrotic regions and interacted with CXCR4+ immune cells.
- Chemotherapy increased senescence in hepatocytes by 5-fold compared to aging and led to distinct CDKN2A+ cell populations.
- Across different conditions, senescent cells exhibited shared characteristics such as AP-1 activation, pro-inflammatory cytokines, and resistance to apoptosis.
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