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Spatiotemporal Transcriptomics Characterizes Immune Microenvironment During Mouse Liver Aging

Year: 2026

Type: article

Abstract: ABSTRACT The liver is a major metabolic organ, responsible for synthesizing and breaking down diverse metabolites. Recently, the liver's immunological functions have gradually been unveiled: combating pathogens and maintaining tissue homeostasis. Age‐related functional alterations in these immune cells emerge as potential drivers of hepatic dysfunction and age‐associated pathologies. However, systematic investigations into spatiotemporal immune cell dynamics during liver aging remain limited. To address this gap, we analyzed young and old mouse livers using single‐cell/nuclei and spatial transcriptomics, revealing T cells as the immune cell population with the most pronounced transcriptomic alterations, marked by enrichment of exhausted CD8 + T cells in aged livers. Spatial mapping showed exhausted CD8 + T cells accumulating in portal vein (PV) zone, co‐localizing with periportal hepatocytes (PP hepatocytes). Up‐regulation of LPIN1 in PP hepatocyte promoted T cell exhaustion. CD8 + T cell exhaustion was tightly associated with disease progression. Therefore, our findings suggest that targeting LPIN1 may alleviate T cell exhaustion, offering potential therapeutic strategies for age‐related liver diseases.

Source: Aging Cell

DOI: 10.1111/acel.70482