Fig. 7.

Aging signal of C. secundus queens in relation to known aging pathways. Shown are simplified IIS (insulin/insulin-like growth factor signaling; blue), TOR (target of rapamycin; green), and ecdysone (brown) pathways and their interactions with an emphasis on (a) ecdysone biosynthesis and (b) protein synthesis and degradation. Red encircled genes were members of the old subnetwork, and thus highly expressed in old queens. Important genes that regulate protein synthesis and degradation are depicted in white. In short, the TOR pathway controls cell growth and metabolism in response to amino acid availability. It is generally composed of two main complexes: TORC1 and TORC2 [67]. Activation of TORC1 promotes mRNA translation, for instance, via S6K /eIF4B / eIF-4a and 4E-BP / eIF4E. Additionally, active TORC1 inhibits autophagy by targeting upstream components necessary for autophagy activation, like Atg1. TOR interacts with IIS, which also regulates multiple physiological functions, including aging. Generally, an active IIS pathway can activate the TORC1 complex via phosphorylation and inactivation of Tsc2 by AKT. AKT inhibits the transcription factor foxo via phosphorylation, which results in the inhibition of transcription of many downstream genes, e.g. involved in lifespan extension, stress response and autophagy. Stress induced Cnc can activate TORC1 in a positive feedback loop (big dashed arrow). It may be responsible for the simultaneous upregulation of protein synthesis and degradation. For more information, see text. Figures are adapted after [65–67]