title: The sirtuin SIRT6 regulates lifespan in male mice.
abstract: The significant increase in human lifespan during the past century confronts us with great medical challenges. To meet these challenges, the mechanisms that determine healthy ageing must be understood and controlled. Sirtuins are highly conserved deacetylases that have been shown to regulate lifespan in yeast, nematodes and fruitflies. However, the role of sirtuins in regulating worm and fly lifespan has recently become controversial. Moreover, the role of the seven mammalian sirtuins, SIRT1 to SIRT7 (homologues of the yeast sirtuin Sir2), in regulating lifespan is unclear. Here we show that male, but not female, transgenic mice overexpressing Sirt6 (ref. 4) have a significantly longer lifespan than wild-type mice. Gene expression analysis revealed significant differences between male Sirt6-transgenic mice and male wild-type mice: transgenic males displayed lower serum levels of insulin-like growth factor 1 (IGF1), higher levels of IGF-binding protein 1 and altered phosphorylation levels of major components of IGF1 signalling, a key pathway in the regulation of lifespan. This study shows the regulation of mammalian lifespan by a sirtuin family member and has important therapeutic implications for age-related diseases.
authors.affiliation: The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel.
authors.forename: Yariv
authors.initials: Y
authors.lastname: Kanfi
authors.forename: Shoshana
authors.initials: S
authors.lastname: Naiman
authors.forename: Gail
authors.initials: G
authors.lastname: Amir
authors.forename: Victoria
authors.initials: V
authors.lastname: Peshti
authors.forename: Guy
authors.initials: G
authors.lastname: Zinman
authors.forename: Liat
authors.initials: L
authors.lastname: Nahum
authors.forename: Ziv
authors.initials: Z
authors.lastname: Bar-Joseph
authors.forename: Haim Y
authors.initials: HY
authors.lastname: Cohen
mesh_terms: D000818:Animals; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D053208:Kaplan-Meier Estimate; D008136:Longevity / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D012727:Sex Characteristics; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*
chemical_list: C519530:insulin-like growth factor-1, mouse; D007334:Insulin-Like Growth Factor I; C501860:Sirt6 protein, mouse; D037761:Sirtuins