αMUPA mice: A transgenic model for longevity induced by caloric restriction

Ruth Miskin, Oren Tirosh, Michal Pardo, Igor Zusman, Betty Schwartz, Shlomo Yahav, Gal Dubnov, Ron Kohen

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Caloric restriction (CR) is currently the only therapeutic intervention known to attenuate aging in mammals, but the underlying mechanisms of this phenomenon are still poorly understood. To get more insight into these mechanisms, we took advantage of the αMUPA transgenic mice that previously were reported to spontaneously eat less and live longer compared with their wild-type control mice. Currently, two transgenic lines that eat less are available, thus implicating the transgenic enzyme, i.e. the urokinase-type plasminogen activator (uPA), in causing the reduced appetite. This phenotypic change could have resulted from the ectopic transgenic expression that we detected in the adult αMUPA brain, or alternatively, from a transgenic interference in brain development. Here, we have summarized similarities and differences so far found between αMUPA and calorically restricted mice. Recently, we noted several changes in the αMUPA liver, at the mitochondrial and cellular level, which consistently pointed to an enhanced capacity to induce apoptosis. In addition, αMUPA mice showed a reduced level of serum IGF-1 and a reduced incidence of spontaneously occurring or carcinogen-induced tumors in several tissues. In contrast, αMUPA did not differ from wild type mice in the levels of low molecular weight antioxidants when compared in several tissues at a young or an old age. Overall, the αMUPA model suggests that fine-tuning of the threshold for apoptosis, possibly linked in part to modulation of serum IGF-1 and mitochondrial functions, could play a role in the attenuation of aging in calorically restricted mice.

Original languageAmerican English
Pages (from-to)255-261
Number of pages7
JournalMechanisms of Ageing and Development
Volume126
Issue number2
DOIs
StatePublished - Feb 2005

Keywords

  • Aging
  • Apoptosis
  • Caloric restriction
  • Mitochondria
  • uPA plasminogen activator
  • αMUPA transgenic mice

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