title: SIRT6 Overexpression Improves Various Aspects of Mouse Healthspan.
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.
authors: The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
authors: Asael
authors: A
authors: Roichman
authors: The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
authors: Yariv
authors: Y
authors: Kanfi
authors: The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
authors: Renana
authors: R
authors: Glazz
authors: The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
authors: Shoshana
authors: S
authors: Naiman
authors: Tamman and Neufeld Cardiovascular Research Institute, Sheba Center of Regenerative Medicine, Sheba Medical Center, Tel Aviv University, Israel.
authors: Uri
authors: U
authors: Amit
authors: Tamman and Neufeld Cardiovascular Research Institute, Sheba Center of Regenerative Medicine, Sheba Medical Center, Tel Aviv University, Israel.
authors: Natalie
authors: N
authors: Landa
authors: The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
authors: Simon
authors: S
authors: Tinman
authors: The Lautenberg Center for Immunology and Cancer Research, IMRIC, Hebrew University Hadassah Medical School, Jerusalem, Israel.
authors: Ilan
authors: I
authors: Stein
authors: The Lautenberg Center for Immunology and Cancer Research, IMRIC, Hebrew University Hadassah Medical School, Jerusalem, Israel.
authors: Eli
authors: E
authors: Pikarsky
authors: Tamman and Neufeld Cardiovascular Research Institute, Sheba Center of Regenerative Medicine, Sheba Medical Center, Tel Aviv University, Israel.
authors: Jonathan
authors: J
authors: Leor
authors: The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
authors: Haim Y
authors: HY
authors: Cohen
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D001774:Blood Chemical Analysis; D001823:Body Composition; D002153:Calorimetry, Indirect; D004247:DNA / Q000032:analysis; D015870:Gene Expression; D005951:Glucose Tolerance Test; D006197:Hair / Q000254:growth & development; D015151:Immunoblotting; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008136:Longevity; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D010641:Phenotype; D012313:RNA / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D037761:Sirtuins / Q000378:metabolism*; D015854:Up-Regulation; D014945:Wound Healing / Q000502:physiology
chemical_list: D012313:RNA; D007334:Insulin-Like Growth Factor I; D004247:DNA; D037761:Sirtuins
keywords: AMPK; Adipose inflammation; Sirtuins; Voluntary activity