SERPINB3 is associated with longer survival in transgenic mice

Sci Rep. 2013 Oct 28:3:3056. doi: 10.1038/srep03056.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging
  • Animals
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / metabolism*
  • Fatty Liver / pathology
  • Female
  • Glycogen / metabolism
  • Hep G2 Cells
  • Humans
  • Interleukin-6 / blood
  • Liver / metabolism
  • Liver / pathology
  • Longevity / genetics*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / metabolism
  • RNA, Messenger / metabolism
  • Serpins / genetics
  • Serpins / metabolism*
  • Shc Signaling Adaptor Proteins / genetics
  • Shc Signaling Adaptor Proteins / metabolism
  • Src Homology 2 Domain-Containing, Transforming Protein 1
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Antigens, Neoplasm
  • Interleukin-6
  • Protease Inhibitors
  • RNA, Messenger
  • Serpins
  • Shc Signaling Adaptor Proteins
  • Shc1 protein, mouse
  • Src Homology 2 Domain-Containing, Transforming Protein 1
  • squamous cell carcinoma-related antigen
  • Glycogen
  • TOR Serine-Threonine Kinases