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. Author manuscript; available in PMC: 2014 May 1.
Published in final edited form as: Trends Endocrinol Metab. 2013 Jan 5;24(5):229–237. doi: 10.1016/j.tem.2012.12.002

Figure 1. Nutrient sensing pathways crosstalk during lifespan.

Figure 1

Several distinct pathways sense dietary input from nutrients in the environment. Amino acids are sensed by the complex TSC1/TSC2 of the TOR pathway. This signal is relayed by a series of mediators, including TOR kinase to the downstream effectors S6K1 and 4E-BP. S6K and 4E-BP enhance translation, and hence, anabolism. Glucose is transported into the cell and converted from ADP and AMP to ATP, which ratios are sensed by the AMPK pathway. AMPK interacts with TSC1/TSC2 to ensure cell homeostasis. Circulating insulin and IGF (IIS) are sensed by the Insulin Receptor (IR) and transmitted to the Insulin Receptor Substrate (IRS, chico in flies). The activated IRS relays the signal to PI3K, which activates AKT, which in turn leads to transcriptional activation of target genes. AKT links the IIS pathway to the glucose sensors and TOR signaling and promotes anabolic processes. Reciprocally, signals from the TOR pathway are relayed via S6K to the IRS in the IIS pathway. As an organism's energy requirements vary throughout lifespan, these signaling pathways operate to maintain energy homeostasis during periods of high demand, such as development and reproduction. Decay in the relays of signals and/or crosstalk leads to aging and age related diseases like insulin resistance, glucose intolerance, diabetes, obesity, metabolic syndrome and cancer.