Vitamin B12 Shields Aging Kidneys by Blocking Glycation and Inflammation

Chronic kidney disease (CKD) is one of the most prevalent and debilitating consequences of biological aging. Key drivers include cellular senescence triggered by advanced glycation end products (AGEs), hyperphosphatemia, oxidative stress, and downstream inflammation and fibrosis. Vitamin B12 deficiency is common in older adults and has been linked to elevated homocysteine, increased AGE formation, and impaired antioxidant defense—but exactly how B12 might protect aging kidneys at the molecular level was poorly understood.

This study used 12-month-old male Wistar rats injected intraperitoneally with D-galactose (300 mg/kg/day for 120 days), a well-validated model of accelerated renal aging. A third group received the same galactose protocol plus dietary vitamin B12 supplementation at 50 µg/kg diet (double the control diet level). Kidney function, injury biomarkers, histopathology, and a broad panel of signaling proteins and gene transcripts were assessed at study end.

Galactose-treated rats showed classic markers of renal dysfunction: elevated urinary albumin, abnormal albumin-creatinine ratios, and upregulated injury markers KIM-1, LCN-2, FABP-1, and TIMP-1. Histology revealed glomerular atrophy, basement membrane thickening, mesangial expansion, and fibrosis. B12 supplementation significantly normalized all these parameters. At the molecular level, B12 reduced accumulation of the AGE marker carboxymethyl-lysine (CML) and its receptor RAGE, and suppressed senescence markers β-galactosidase and p53.

On the phosphate regulation front, galactose treatment elevated plasma phosphate, reduced vitamin D, increased FGF23, and decreased Klotho—a pattern consistent with accelerated renal aging. B12 reversed each of these changes, restoring the Klotho-FGF23 axis and upregulating vitamin D receptor (VDR) and CYP27b1 gene expression while suppressing PTH. For inflammation, B12 downregulated TLR4, MCP-1, ICAM, VCAM, NF-kB, TNF-α, and IL-6. Fibrosis was attenuated via suppression of TGF-β and modulation of the pPERK-GSK3β-N-cadherin pathway, with restoration of telomerase components (TERT, TERC, TERF). Apoptosis markers (Bax, caspase-3) were reduced and pro-survival Bcl-2 was preserved. Podocyte integrity markers nephrin and podocin were also protected.

These findings position vitamin B12 as a multi-target nutritional intervention for renal aging, acting simultaneously on AGE accumulation, phosphate dysregulation, inflammation, fibrosis, and apoptosis. While the study is preclinical and specific to male rats, the mechanistic breadth is compelling and supports investigation of B12 supplementation in elderly populations at risk for CKD.