Aging reshapes cardiac extravascular leukocyte transcription through bidirectional remodeling during LPS-induced endotoxemia

In aged C57BL/6 mice, LPS-induced endotoxemia triggers bidirectional single-cell transcriptional remodeling in cardiac extravascular leukocytes, with reduced mitochondrial-associated programs across macrophages, T cells, and B cells.

• Why it matters: Sepsis and cardiac dysfunction are more severe in older adults, but the aging-specific transcriptional programs of cardiac immune cells during systemic inflammation are not well defined.
• What they did: Young and aged mice received intraperitoneal LPS (5 mg/kg) or vehicle, and cardiac extravascular leukocytes from retrogradely perfused hearts were profiled by single-cell RNA sequencing 24 h later.
• The result: Aging linked to up- and downregulated gene programs after LPS, including increased tissue-remodeling/repair in macrophage lineages and altered metabolic, actin, Th17, cytotoxicity, and antigen-presentation programs in T and B cells.

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