Details of breeding and husbandry, including preparation of encapsulated (enteric-released) rapamycin, have been described at length in earlier papers (Miller et al. 2007 (link); Miller et al. 2011 (link); Strong et al. 2013 (link)), as have results of both end-of-life (Miller et al. 2011 (link)) and midlife (Wilkinson et al. 2012 (link)) necropsy analyses. In brief, genetically heterogeneous UM-HET3 mice were produced by a cross between CByB6F1/J mothers (JAX #100009) and C3D2F1/J fathers (JAX #100004), at each of three test sites: the Jackson Laboratory (TJL), the University of Michigan (UM), or the University of Texas Health Science Center at San Antonio (UT). They were housed at 3 male mice or 4 female mice per cage from weaning, and at nine months of age were given a diet containing encapsulated rapamycin at 4.7, 14, or 42 ppm (mg of drug per kg of food). Mice that died were not replaced, so cage density declined at older ages. Cages were inspected daily. Date of death was noted for mice found dead, and mice found to be so ill that they were expected to die within the next 24 – 48 hr were euthanized, with the date of euthanasia taken as the date of death for life table calculations. At the time of analysis, 532 control mice had died, and 2 control mice (0.4%) were alive; 749 mice exposed to rapamycin had died, and 15 (1.9%) were alive. In addition, 5 mice were removed prior to natural death because of experimental accidents (example: death during implantation of ID tag); 6 were removed for humane reasons because of dermatitis; 74 males were removed according to our protocol policy which requires euthanasia of all mice in cages in which any mouse is found to have extensive fight wounds (Miller et al. 2007 (link)); and 104 mice, all at TJL, were removed for use in a separate study of immune function.