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

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


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 languageEnglish
Pages (from-to)603-615
Number of pages13
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Issue number5
StatePublished - 2017
Externally publishedYes


  • AMPK
  • Adipose inflammation
  • Sirtuins
  • Voluntary activity


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