A critical analysis of the role of growth hormone and IGF-1 in aging and lifespan.
Studies in Caenorhabditis elegans demonstrate that disruption of the daf-2 signaling pathways extends lifespan. Similarities among the daf-2 pathway, insulin-like signaling in flies and yeast, and the mammalian insulin-like growth factor 1 (IGF-1) signaling cascade raise the possibility that modifications to IGF-1 signaling could also extend lifespan in mammals. In fact, growth hormone (GH)/IGF-1-deficient dwarf mice do live significantly longer than their wild-type counterparts. However, multiple endocrine deficiencies and developmental anomalies inherent in these models confound this interpretation. Here, we critique the current mammalian models of GH/IGF-1 deficiency and discuss the actions of GH/IGF-1 on biological aging and lifespan.
Carter
Christy S
CS
Dept Internal Medicine, Section on Gerontology and Geriatrics, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1083, USA.
Ramsey
Melinda M
MM
Sonntag
William E
WE
D000375:Aging / Q000502:physiology*; D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology; D029742:Caenorhabditis elegans Proteins; D004392:Dwarfism / Q000378:metabolism; D013006:Growth Hormone / Q000172:deficiency / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D023421:Models, Animal; D051381:Rats; D011972:Receptor, Insulin / Q000502:physiology
D029742:Caenorhabditis elegans Proteins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin