TY - JOUR
T1 - SIRT6 overexpression improves various aspects of mouse healthspan
AU - Roichman, Asael
AU - Kanfi, Yariv
AU - Glazz, Renana
AU - Naiman, Shoshana
AU - Amit, Uri
AU - Landa, Natalie
AU - Tinman, Simon
AU - Stein, Ilan
AU - Pikarsky, Eli
AU - Leor, Jonathan
AU - Cohen, Haim Y.
N1 - Publisher Copyright:
© The Author 2016.
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
KW - AMPK
KW - Adipose inflammation
KW - Sirtuins
KW - Voluntary activity
UR - http://www.scopus.com/inward/record.url?scp=85019973023&partnerID=8YFLogxK
U2 - 10.1093/gerona/glw152
DO - 10.1093/gerona/glw152
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C2 - 27519885
AN - SCOPUS:85019973023
SN - 1079-5006
VL - 72
SP - 603
EP - 615
JO - Journals of Gerontology - Series A Biological Sciences and Medical Sciences
JF - Journals of Gerontology - Series A Biological Sciences and Medical Sciences
IS - 5
ER -