Increased lifespan in hyposulfatemic NaS1 null mice

Exp Gerontol. 2011 Oct;46(10):833-5. doi: 10.1016/j.exger.2011.05.008. Epub 2011 May 30.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging* / metabolism
  • Aging* / physiology
  • Animals
  • Cation Transport Proteins / genetics*
  • Female
  • Homeostasis
  • Liver / metabolism*
  • Longevity / physiology*
  • Male
  • Mice
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sodium / metabolism*
  • Sulfates / metabolism*

Substances

  • Cation Transport Proteins
  • Sulfates
  • Sodium