Figure 11: Schematic diagram depicting the proposed differential regulations of MIF-induced of control of the AMPK-mTOR-dependent autophagy pathways in cardiac homeostasis (young) and cardiac dysfunction (aging).

Aging suppresses MIF levels, leading to a less pronounced AMPK activation. Activation of AMPK inhibits mTOR and turns on autophagy, thus resulting in the preserved ATP content and cardiac homeostasis. AMPK-mediated autophagy and ATP content are reduced in aging, prompting cardiac dysfunction. Box, letter and line sizes refer to the levels or potencies of signaling molecules or events. Aging promotes IκB/NFκB-mediated myocardial inflammation, the effect of which is alleviated by MIF deficiency independent of autophagy process. Arrows denote stimulation whereas “T” ending represent inhibition. MIF: Microphage migration factor, AMPK: AMP-activation protein kinase; mTOR: mammalian target of rapamycin.