Open AccessCharacterization of physiological defects in adult SIRT6-/- mice
Author(s) -
Victoria Peshti,
Alexey Obolensky,
Liat Nahum,
Yariv Kanfi,
M. Rathaus,
Maytal Avraham,
Simon Tinman,
F W Alt,
Eyal Banin,
Haim Cohen
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0176371
Subject(s) - sirt6 , phenotype , biology , endocrinology , sirtuin , retinal , medicine , knockout mouse , premature aging , nad+ kinase , ratón , physiology , genetics , biochemistry , receptor , gene , enzyme
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.