The Snell dwarf mutation Pit1^dw can increase life span in mice

Over the past 30 years, the Snell dwarf mutation (Pit1^dw) has been reported to shorten, to have no effect on, or to increase life span in various colonies; however, few details of these disparate results have been published. We now report that mean, median, and maximum life spans are increased by 40-50% for Snell dwarf (Pit1^dw/Pit1^dw) DW/J females, and 25-50% for dwarf DWC3F1 males and females with the compound heterozygous Pit1^dw/Pit1^dw-J genotype. We previously observed aspects of delayed senescence in Snell dwarf (Pit1^dw/Pit1^dw) DW/J males; however, their median life span was shortened by about 25% (Genetic Effects on Aging II, 1990, The Telford Press, Caldwell, NJ, pp. 435-456). This short life span was not an intrinsic effect of the mutation, but a consequence of housing male dwarfs with normal-sized male littermates; our present results demonstrate that Snell dwarf males attain very long life spans when housed with normal-sized females. We conclude that the dwarf mutation interacts with environmental factors to alter life spans and, probably, rates of ageing, over an extremely broad range. We propose that this variation in the effect of the Snell dwarf mutation results from a tradeoff between physical vigor and life span that is mediated by pituitary hormones, and that growth hormone, thyroid hormone, and possibly prolactin regulate mechanisms that schedule mortality in mammals.