Figure 2
From: Diminished mTOR signaling: a common mode of action for endocrine longevity factors
Regulation of PI3K/Akt/mTOR signaling by growth hormone, IGF-1, leptin and adiponectin. Growth hormone signaling promotes the expression of IGF-1 by the liver and adipose tissue, which signals through the insulin/IGF-1 receptor to promote PI3K/Akt/mTORC1 signaling and aging. Several mutant mice, such as the Ames Dwarf mouse, are deficient for the production of growth hormone, and consequently have low IGF-1 levels and low mTORC1 activity in IGF-1 sensitive tissues. Growth hormone also normally represses adiponectin, a hormone from white adipose tissue that inhibits mTORC1 activity by activating AMPK. Leptin promotes PI3K/Akt/mTOR signaling via the Jak2-mediated phosphorylation of insulin receptor substrate. Leptin also promotes IGF-1 signaling by stimulating the GH/IGF-1 axis. Functions such as translation and autophagy that impact aging are shown in a green box if stimulated by PI3K/Akt/mTORC1 activity, and gray box if inhibited by PI3K/Akt/mTORC1 activity.