Figure 1.

Possible link between accumulation of amino-acid pools, mitochondrial function, and the insulin and TOR pathways in C. elegans longevity. Black lines indicate the activating or repressive function of members of different signal transduction pathways. Amino-acid pools and other nutrients activate TOR signaling, which then results in increased translation following activation of the protein kinase S6K and the translation initiation factor eIFE4 and inhibition of mitochondrial biogenesis. However, mutations in DAF-2/IGF1R result in the activation of DAF-16, which represses daf-15 transcription to reduce TOR signaling. Red arrows indicate the effects of mutations on cellular amino-acid pools. Specifically, Fuchs et al. [7] show that mutations in daf-2/IGF1R, daf-28/insulin and ife-2/eIFE4 cause an increase in amino acid levels, especially branched-chain amino acids. Falk et al. [9] showed that mutations affecting complexes I, II and III of the electron transport chain (ETC), including some that increase life span, also result in accumulation of branched-chain amino acids. Mutations that confer longevity through different pathways share the metabolic signature of increased branched-chain amino-acid pools.