Restoration of aged liver regeneration by youthful systemic factors via LTβ-driven hepatocyte reprogramming.

Young systemic factors, especially B-cell-derived lymphotoxin β, restore aged liver regeneration by inducing transient hepatocyte reprogramming via LTβ/LTBR signaling, with a 70% regeneration boost in mice.

• Why it matters: Liver regenerative capacity declines with age, limiting treatment options for elderly patients and transplant success. Understanding how youthful factors rejuvenate aged liver tissue could improve clinical outcomes and develop anti-aging therapies.
• What they did: Researchers analyzed human liver grafts and used heterochronic parabiosis in mice, combining single-cell transcriptomics and lineage tracing to identify mechanisms. They focused on the role of LTβ/LTBR signaling and B-cell effects in promoting regeneration.
• The result: Activation of LTβ/LTBR signaling by young B cells enhances hepatocyte reprogramming and accelerates regeneration in aged livers, suggesting LTβ-based therapies could improve recovery and extend transplant viability in older populations.