SIRT6 overexpression improves various aspects of mouse healthspan

Asael Roichman; Yariv Kanfi; Renana Glazz; Shoshana Naiman; Uri Amit; Natalie Landa; Simon Tinman; Ilan Stein; Eli Pikarsky; Jonathan Leor; Haim Y. Cohen

doi:10.1093/gerona/glw152

SIRT6 overexpression improves various aspects of mouse healthspan

Asael Roichman, Yariv Kanfi, Renana Glazz, Shoshana Naiman, Uri Amit, Natalie Landa, Simon Tinman, Ilan Stein, Eli Pikarsky, Jonathan Leor, Haim Y. Cohen^*

^*Corresponding author for this work

Department of Immunology and Cancer Research

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

45 Scopus citations

Abstract

The extension in human lifespan in the last century results in a significant increase in incidence of age related diseases. It is therefore crucial to identify key factors that control elderly healthspan. Similar to dietary restriction, mice overexpressing the NAD+ dependent protein deacylase SIRT6 (MOSES) live longer and have reduced IGF-1 levels. However, it is as yet unknown whether SIRT6 also affects various healthspan parameters. Here, a range of age related phenotypes was evaluated in MOSES mice. In comparison to their wild-type (WT) littermates, old MOSES mice showed amelioration of a variety of age-related disorders, including: improved glucose tolerance, younger hormonal profile, reduced age-related adipose inflammation and increased physical activity. The increased activity was accompanied with increased muscle AMP-activated protein kinase (AMPK) activity. Altogether, these results indicate that overexpression of SIRT6 in mice retards important aspects of the aging process and suggest SIRT6 to be a potential therapeutic target for the treatment of a set of age-related disorders.

Original language	English
Pages (from-to)	603-615
Number of pages	13
Journal	Journals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume	72
Issue number	5
DOIs	https://doi.org/10.1093/gerona/glw152
State	Published - 2017

Bibliographical note

Funding Information:
This work was supported by the Israel Science Foundation (#621/13), I-Core Foundation (#41/11), Israeli Ministry of Health (#3.9194), TEVA NNE Program (#PO 1237680), ESFD, D-Cure, Israel Cancer Association (#2016-0103) and the ERC: European Research Council (#242765).

Publisher Copyright:
© The Author 2016.

Keywords

AMPK
Adipose inflammation
Sirtuins
Voluntary activity

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abstract = "The extension in human lifespan in the last century results in a significant increase in incidence of age related diseases. It is therefore crucial to identify key factors that control elderly healthspan. Similar to dietary restriction, mice overexpressing the NAD+ dependent protein deacylase SIRT6 (MOSES) live longer and have reduced IGF-1 levels. However, it is as yet unknown whether SIRT6 also affects various healthspan parameters. Here, a range of age related phenotypes was evaluated in MOSES mice. In comparison to their wild-type (WT) littermates, old MOSES mice showed amelioration of a variety of age-related disorders, including: improved glucose tolerance, younger hormonal profile, reduced age-related adipose inflammation and increased physical activity. The increased activity was accompanied with increased muscle AMP-activated protein kinase (AMPK) activity. Altogether, these results indicate that overexpression of SIRT6 in mice retards important aspects of the aging process and suggest SIRT6 to be a potential therapeutic target for the treatment of a set of age-related disorders.",

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AU - Landa, Natalie

AU - Tinman, Simon

AU - Stein, Ilan

AU - Pikarsky, Eli

AU - Leor, Jonathan

AU - Cohen, Haim Y.

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SIRT6 overexpression improves various aspects of mouse healthspan

Abstract

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Keywords

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