13 Extended Life Span in Mice with Reduction in the GH/IGF-1 Axis

Abstract

In the quest to identify factors that contribute to aging, a group of closely related molecules have repeatedly emerged as critical players. Insulin-like growth factor-1 (IGF-1)-like proteins and their downstream intracellular signaling molecules have been shown to be associated with life span in fruit flies and nematodes (Clancy et al. 2001; Tatar et al. 2001). More recently, several mouse models with reduced growth hormone (GH) and/or IGF-1 signaling have also been shown to have extended life spans as compared to control/normal siblings. Evaluation of these mouse models, as well as mice with altered GH signaling that do not show increased life span, has offered some clues as to factors that contribute to aging. For example, it is clear that the role of the GH/IGF-1 axis overlaps partially but is distinct from the effect of calorie restriction, a well-recognized means to delay aging (Bonkowski et al. 2006). Although the mechanisms linking the GH/IGF-1 axis with delayed aging remain to be determined, there are some commonalities among the various strains of long-lived mice, such as reduced IGF-1 signaling, enhanced insulin sensitivity, improved stress resistance, and protection from carcinogenesis, which likely contribute to the improvement in longevity. Future studies comparing these mouse models will undoubtedly provide valuable insight into additional factors that contribute to the extension of life span. GH/IGF-1 AXIS Overview The GH/IGF-1 axis refers to the combined actions of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) (Fig. 1). GH is produced and secreted by somatotrophic cells of the anterior pituitary...