Research Paper Volume 11, Issue 15 pp 5726—5743

Figure 6. Working model showing glucose suppression of ROS hormesis to accelerate aging. (A) Oxidative stress at early stage may induce hormetic ROS, which in turn wages oxidative stress response by activating transcription factors (TFs) such as SKN-1. Glucose can suppress such hormetic ROS, therefore inhibiting TFs such as SKN-1. The suppression of hormetic ROS by glucose leads to uncontrolled elevation of ROS later in life and organismal death. (B) ROS accumulates as organisms age. Early in life, low levels of ROS serve as signaling to induce oxidative stress response, which in turns slower oxidative damage later in life. The ROS in early life serves a hormetic signal. glp-1 and isp-1 induce hormetic ROS and live longer than WT animals. However, glucose suppression of such hormetic ROS accelerates ROS accumulation and blocks lifespan extension in these long-lived mutants.