Insulin-like peptides (ILPs) regulate IIS function. In Drosophila melanogaster, there are seven Drosophila ILP (dilp) genes. One of which is dilp2, a gene that encodes a peptide that closely mimics human insulin. Insulin-producing cells (IPCs) are analogous in function to pancreatic β cells in mammals. In Drosophila hemolymph, IPCs are necessary for carbohydrate homeostasis. When IPCs are explicitly removed, developmental delays occur growth is hindered. Late-life mortality is diminished in these model organisms, suggesting that life span is regulated by dilps secreted from these pancreatic β cells.
c. In specific target tissues, dilps activate the insulin-like growth factor receptor (InR). InR signals through chico, a homolog of the mammalian insulin receptor substrates, PI3 kinase (PI3K), as well as Akt.
d. PTEN phosphatase provokes PI3K activity and therefore IIS. IIS affects gene expression by causing inactivation of the Forkhead Box O transcription factor FOXO. Down-regulation of target genes occurs due to Akt-mediated phosphorylation and cytoplasmic retention of FOXO. During periods of decreased IIS activity, the activation of FOXO has an effect on growth and the longevity of the organism.
e. In Caenorhabditis elegans, the FOXO homolog is daf-16. In mutants, who possess the dysfunction of IIS, daf-16 plays an important role in the longevity …show more content…
Mus musculus
i. In animal models, dietary restriction is shown to provide as another link between insulin/IGF-1 signaling and life span. An increase in insulin sensitivity and enhanced glucose tolerance were seen among primates who were subjected to a routine of dietary restriction. Another result in a rat model showed how calorie restriction lowered their levels of IGF-1 which contributed to the protective effect against pathologies that are associated with age. ii. In mice, lifespan was increased and metabolism was enhanced due to suppression of mTORC1. mTOR is an evolutionary conserved serine/threonine kinase that acts downstream of the insulin signaling pathway. The two functional complexes of mTOR are mTORC1 and mTORC2. As an energy sensor, mTORC1 is activated by nutrients such as amino acids and glucose, cellular energy levels, and many growth factors/hormones such as insulin and IGF-1. Regulation of key cellular events is also a role of mTORC1 including cell growth, proliferation, differentiation, gene transcription, mRNA translation, autophagy, survival, and metabolism. Suppression of mTOR signaling extends lifespan in yeast, worms, flies, and mice. mTOR signaling suppression has also been found to attenuate various age-related diseases. These diseases include obesity, neurodegenerative diseases, osteoporosis, osteoarthritis, and age-related macular