Research Paper Volume 4, Issue 5 pp 350—358

Figure 2. Low mTOR/S6K activity: insulin sensitivity plus longevity.

(A) Calorie restriction. Deactivation of the nutrient-sensing mTOR pathway results in insulin sensitivity.

(B) Knockout of S6K1 in mice abolishes feedback block of insulin signaling, resulting in insulin sensitivity [94].

(C) Decreased levels of growth hormone (GH). In mice, absence of GH or GH receptor leads to a remarkable extension of longevity [95]. GH receptor deficiency is associated with a reduction in pro-aging signaling, cancer, and diabetes in humans [96]. Growth hormone signaling accelerates aging in mammals [97]. Remarkably, growth stimulation promotes cellular aging, when cells cannot proliferate [98, 99]. Thus, the growth promoting pathways such as mTOR are involved in both organismal and cellular aging.

(D) Acute treatment with rapamycin. Deactivation of the nutrient-sensing mTOR pathway abolishes a feedback block of insulin signaling, resulting in insulin sensitivity [50].