RNA Sequencing of Mouse Liver Post Caloric Resrtiction and Anti-Anging Interventions

It has been previously reported that a SERPINE1 mutation in an Amish cohort links to a 10-year lifespan increase and improved metabolism. SERPINE1 encodes for Plasminogen Activator Inhibitor-1 (PAI-1) which is a clinical predictor of vascular stiffness, hypertension, and diastolic dysfunction.

Moreover, PAI-1 amplifies accumulation of senescent cells as a component of the senescence associated secretory phenotype (SASP). Here, we compared hepatic transcriptomic profiles in mice after 8 weeks of CR, rapamycin, metformin, or the PAI-1 inhibitor TM5614 versus an ad libitum control. CR induced extensive changes (1087 genes downregulated, 1145 upregulated), while TM5614 showed the closest mimicry (211 down, 218 up), sharing ~50% of CR’s differentially expressed genes, including downregulated Il11ra1 and upregulated Per2, tied to longevity and metabolism.