Increased lifespan in hyposulfatemic NaS1 null mice.

Sulfate (SO(4)(2-)) plays an important role in mammalian growth and development. In this study, hyposulfatemic NaS1 null (Nas1-/-) mice were used to investigate the consequences of perturbed SO(4)(2-) homeostasis on longevity. Median life spans were increased (by ≈25%) in male and female Nas1-/- mice when compared with Nas1+/+ mice. At 1 yr of age, serum SO(4)(2-) levels remained low in Nas1-/- mice (≈0.16 mM) when compared to Nas1+/+ mice (≈0.96 mM). RT-PCR revealed increased hepatic mRNA levels of Sirt1 (by ≈60%), Cat (by ≈48%), Hdac3 (by ≈22%), Trp53 and Cd55 (by ≈36%) in Nas1-/- mice, genes linked to ageing. Histological analyses of livers from 2 yr old mice revealed neoplasms in >50% of Nas1+/+ mice but not in Nas1-/- mice. This is the first study to report increased lifespan, decreased hepatic tumours and increased hepatic expression of genes linked to ageing in hyposulfatemic Nas1-/- mice, implicating a potential role of SO(4)(2-) in mammalian longevity and cancer. Crown