title: Increased lifespan in hyposulfatemic NaS1 null mice.
abstract: 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.
authors.affiliation: Molecular Physiology Group, School of Biomedical Sciences, University of Queensland, Brisbane, QLD 4072, Australia. d.markovich@uq.edu.au
authors.forename: Daniel
authors.initials: D
authors.lastname: Markovich
authors.forename: Mei-Chun
authors.initials: MC
authors.lastname: Ku
authors.forename: Dzaidenny
authors.initials: D
authors.lastname: Muslim
mesh_terms: D000375:Aging / Q000378:metabolism / Q000502:physiology; D000818:Animals; D027682:Cation Transport Proteins / Q000235:genetics*; D005260:Female; D006706:Homeostasis; D008099:Liver / Q000378:metabolism*; D008136:Longevity / Q000502:physiology*; D008297:Male; D051379:Mice; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012964:Sodium / Q000378:metabolism*; D013431:Sulfates / Q000378:metabolism*
chemical_list: D027682:Cation Transport Proteins; D013431:Sulfates; D012964:Sodium