Longevity & Aging

Serine Metabolism Breakdown Drives Kidney Aging — And Fixing It May Slow CKD

Researchers discovered that angiotensin II suppresses the enzyme PGK1 in podocytes — kidney filtration cells — by activating the transcription factor FOXA1. This reduces L-serine biosynthesis from the glycolytic intermediate 3-phosphoglycerate, triggering mitochondrial dysfunction, actin cytoskeleton collapse, lipid accumulation, and cellular senescence. The serine deficit also shifts sphingolipid metabolism toward toxic deoxysphingolipids via the PI3K/AKT pathway. Restoring serine levels or re-expressing PGK1 in mouse CKD models reversed these effects. PGK1 was also found to physically stabilize podocyte cytoskeleton via interaction with keratin KRT1, revealing a dual metabolic-structural role for this enzyme.