Protective Role of p66Shc Deletion in Physiological Renal Aging: Effects on G Protein-Coupled Receptor 124 Expression and Associated Cellular Senescence.

ABSTRACT: The adaptor protein p66Shc regulates oxidative stress and aging, but its role in renal aging is unclear. We investigated the effects of p66Shc deletion on age-related kidney changes, focusing on G protein-coupled receptor 124 (GPR124) and cellular senescence. Using kidney and urine samples from p66Shc^-/- and wild-type mice aged 5-24 months, we found that p66Shc deficiency slows renal aging. Compared to wild-type mice, p66Shc^-/- mice showed better kidney function and reduced glomerular sclerosis and mesangial expansion from 18 months, alongside attenuated fibrosis, oxidative stress, and podocyte loss. Age-related declines in GPR124 were also smaller in p66Shc^-/- mice, correlating with lower p16^INK4a levels in glomeruli and cultured podocytes. Thes

SUBMITTER: Iacobini C 

PROVIDER: S-EPMC12652738 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature