Hepatic gene and protein expression of primary components of the IGF-I axis in long lived Snell dwarf mice

Recent evidence indicates that the GH/IGF-I axis plays a key role in the control of aging and longevity. To better understand this biological relationship we examined the mRNA and corresponding protein levels of primary IGF-I axis genes in the livers of young and aged long-lived Snell dwarf mice relative to their age-matched controls. We demonstrated that the level of IGF-I and ALS mRNAs is dramatically decreased in both young and aged dwarf livers, transcripts encoding IGF-IR and IGFBP-I are elevated in young dwarfs, but normalize to control levels in aged dwarf livers while transcripts encoding IGFBP-3 are elevated only in aged controls. Interestingly, regulation at the protein level of several IGF-I axis components in the Snell dwarf appears to involve both altered gene expression and post-translational regulation. In this study, we reveal both concordant and discordant relationships between mRNA and protein levels for particular components of the IGF-I axis, illustrating that some of these gene products are not solely regulated by transcriptional mechanisms. These results are consistent with a delay in the molecular maturation of the IGF-I axis in dwarf livers, suggesting the preservation of some neonatal characteristics in young adult and aged dwarf livers. Our studies provide gene expression and protein abundance profiles for components of IGF-I axis that are distinguishing characteristics of both young and aged dwarf mice, and suggest that delayed development of the IGF-I axis in the young adult Pit1(dw/dwJ) dwarf liver may play an important role in the endocrine regulation of mammalian longevity. (c) 2005 Elsevier Ireland Ltd. All rights reserved.