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. 2021 Oct 1;12(7):1713–1728. doi: 10.14336/AD.2021.0225

Figure 1.

Figure 1.

Organ responses based on the Akt/FoxOs axis during aging. Impaired insulin signaling, insulin resistance induces metabolic changes called “aging metabolism” in metabolic organs during aging. The insulin resistance in metabolic organs and tissues such as the liver, muscles, and adipose tissues causes hyperinsulinemia accompanied by Akt inactivation, which increases FoxOs activity (Akt/FoxOs/PPARγ axis upregulation) leading to lipid accumulation. In contrast, the hyperinsulinemia induces Akt activation and inhibits FoxOs activity (Akt/FoxOs/MnSOD axis downregulation) leading to decreases the expression of FoxOs-dependent antioxidant genes such as MnSOD and catalase in non-metabolic organs including the kidneys and the lungs failing to suppress oxidative stress and age-related inflammation. However, CR modulates insulin resistance and hyperinsulinemia, and alleviates age-related inflammation. CR, Calorie restriction; MTP, Microsomal triacylglycerol transfer protein; SOD, Superoxide dismutase; ROS, Reactive oxygen species.