title: SERPINB3 is associated with longer survival in transgenic mice.
abstract: The physiological roles of the protease inhibitor SERPINB3 (SB3) are still largely unknown. The study was addressed to assess the biological effects of this serpin in vivo using a SB3 transgenic mouse model. Two colonies of mice (123 transgenic for SB3 and 148 C57BL/6J controls) have been studied. Transgenic (TG) mice showed longer survival than controls and the difference was more remarkable in males than in females (18.5% vs 12.7% life span increase). In TG mice decreased IL-6 in serum and lower p66shc in the liver were observed. In addition, TG males showed higher expression of mTOR in the liver. Liver histology showed age-dependent increase of steatosis and decrease of glycogen storage in both groups and none of the animals developed neoplastic lesions. In conclusion, the gain in life span observed in SB3-transgenic mice could be determined by multiple mechanisms, including the decrease of circulating IL-6 and the modulation of ageing genes in the liver.
authors.affiliation: Dept of Medicine, University of Padua, Via Giustiniani, 2 - 35128 Padua, Italy.
authors.forename: Gianmarco
authors.initials: G
authors.lastname: Villano
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: Ruvoletto
authors.forename: Giulio
authors.initials: G
authors.lastname: Ceolotto
authors.forename: Santina
authors.initials: S
authors.lastname: Quarta
authors.forename: Fiorella
authors.initials: F
authors.lastname: Calabrese
authors.forename: Cristian
authors.initials: C
authors.lastname: Turato
authors.forename: Natascia
authors.initials: N
authors.lastname: Tono
authors.forename: Marika
authors.initials: M
authors.lastname: Crescenzi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Biasiolo
authors.forename: Arianna
authors.initials: A
authors.lastname: Cattelan
authors.forename: Carlo
authors.initials: C
authors.lastname: Merkel
authors.forename: Angelo
authors.initials: A
authors.lastname: Avogaro
authors.forename: Angelo
authors.initials: A
authors.lastname: Gatta
authors.forename: Patrizia
authors.initials: P
authors.lastname: Pontisso
mesh_terms: D000375:Aging; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D005234:Fatty Liver / Q000473:pathology; D005260:Female; D006003:Glycogen / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008136:Longevity / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011480:Protease Inhibitors / Q000737:chemistry / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015843:Serpins / Q000235:genetics / Q000378:metabolism*; D055765:Shc Signaling Adaptor Proteins / Q000235:genetics / Q000378:metabolism; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D015850:Interleukin-6; D011480:Protease Inhibitors; D012333:RNA, Messenger; D015843:Serpins; D055765:Shc Signaling Adaptor Proteins; C528034:Shc1 protein, mouse; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; C051072:squamous cell carcinoma-related antigen; D006003:Glycogen; D058570:TOR Serine-Threonine Kinases