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

doi:10.1371/journal.pone.0176371

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

The Mina and Everard Goodman Faculty of Life Sciences - at Bar-Ilan University

Research output: Contribution to journal › Article › peer-review

34 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 language	English
Article number	e0176371
Journal	PLoS ONE
Volume	12
Issue number	4
DOIs	https://doi.org/10.1371/journal.pone.0176371
State	Published - Apr 2017

Bibliographical note

Publisher Copyright:
© 2017 Peshti et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding

We thank the members of the Cohen lab, in particular Shoshana Naiman, for their helpful comments on the manuscript. This study was supported by the Israeli Academy of Sciences, I-Core, Binational US-Israel Science Foundation, Israel Cancer Association, Koret Foundation, Israel Cancer Research Fund, the Israel Ministry of Health, Lir’ot association, TEVA NNE program, EFSD, D- Cure, the ERC: European Research Council and the Yedidut Research Fund.

Funders	Funder number
D- Cure
Israel Ministry of Health, Lir’ot association
Israeli Academy of Sciences
Yedidut Research Fund
Koret Foundation
Israel Cancer Research Fund
Teva Pharmaceutical Industries
European Commission
European Foundation for the Study of Diabetes
Israel Cancer Association
Israel Science Foundation
Israeli Centers for Research Excellence

Access to Document

10.1371/journal.pone.0176371

Cite this

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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.",

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AU - Avraham, Maytal

AU - Tinman, Simon

AU - Alt, Fredrick W.

AU - Banin, Eyal

AU - Cohen, Haim Y.

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