Characterization of physiological defects in adult SIRT6-/- mice

Victoria Peshti, Alexey Obolensky, Liat Nahum, Yariv Kanfi, Moran Rathaus, Maytal Avraham, Simon Tinman, Fredrick W. Alt, Eyal Banin, Haim Y. Cohen

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

The NAD+-dependent SIRT6 deacetylase was shown to be a major regulator of lifespan and healthspan. Mice deficient for SIRT6 develop a premature aging phenotype and metabolic defects, and die before four weeks of age. Thus, the effect of SIRT6 deficiency in adult mice is unknown. Here we show that SIRT6-/- mice in mixed 129/SvJ/BALB/c background reach adulthood, allowing examination of SIRT6-related metabolic and developmental phenotypes in adult mice. In this mixed background, at 200 days of age, more than 80% of the female knock-out mice were alive whereas only 10% of male knock-out mice survived. In comparison to their wild-type littermates, SIRT6 deficient mice have reduced body weight, increased glucose uptake and exhibit an age-dependent progressive impairment of retinal function accompanied by thinning of retinal layers. Together, these results demonstrate a role for SIRT6 in metabolism and age-related ocular changes in adult mice and suggest a gender specific regulation of lifespan by SIRT6.

Original languageEnglish
Article numbere0176371
JournalPLoS ONE
Volume12
Issue number4
DOIs
StatePublished - 1 Apr 2017
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology (all)
  • Agricultural and Biological Sciences (all)
  • General

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