GH/insulin/IGF-1 signaling is a vital pathway e.g. in the regulation of protein 
synthesis and glucose metabolism. However, mouse dwarf strains which exhibit 
reduced GH secretion and subsequently a decline in IGF-1 signaling can live 
longer than their wild type counterparts. There is striking evidence indicating 
that the IGF-1/PI-3K/AKT signaling enhances growth of animals during development 
but later in life can potentiate the aging process. This conserved pleiotropy 
has been called the insulin/IGF-1 paradox. In Caenorhabditiselegans, the decline 
in this pathway activates the DAF-16 gene, an ortholog of mammalian FoxO genes, 
which regulate stress resistance and longevity. The mammalian PI-3K/AKT pathway 
also activates the NF-kappaB signaling that inhibits apoptosis and triggers 
inflammatory responses. Many longevity genes, e.g. FoxOs and SIRT1, are 
inhibitors of NF-kappaB signaling. We will discuss the evidence that 
insulin/IGF-1 signaling can enhance the NF-kappaB signaling and subsequently 
potentiate the aging process and aggravate age-related degenerative diseases.