αMUPA mice: A transgenic model for increased life span

αMUPA is a line of transgenic mice that, compared with their wild type (WT) counterparts, spontaneously eat less (~20%) and live longer (average ~20%), thus resembling dietary-restricted (DR) mice. Here, we show that body temperature was significantly reduced in αMUPA compared with WT throughout a wide range of ages. Plasma corticosterone was significantly higher in young αMUPA compared to young WT; however, it significantly declined in aged αMUPA, but not in aged WT. In addition, age-associated thymus involution occurred in αMUPA as it did in WT. Thus αMUPA mice appear to largely resemble, but also to somewhat differ from diet-restricted animals. We also report on four new transgenic lines that, like αMUPA, produced in the brain the mRNA that encodes the extracellular protease urokinase (uPA); however, transgenic uPA expression was most extensive and widespread in the αMUPA brain, where it also occurred in the hypothalamus. αMUPA was also the only line that ate less, but also showed another characteristic, high frequency leg muscle tremor seen only at unstable body states. We hypothesize that transgenic uPA in the brain could have caused the αMUPA phenotypic alterations. Thus αMUPA offers a unique transgenic model of inherently reduced eating to investigate the homeostatic state of delayed aging at the systemic and single-cell levels. Copyright (C) 1999 Elsevier Science Inc.