Anti-Aging Drug Discovery on the Basis of Hallmarks of Aging by unknow

Author:unknow
Language: eng
Format: epub, pdf
ISBN: 9780323902366
Publisher: Elsevier
Published: 2022-09-15T00:00:00+00:00

Figure 9.1 A complex crosstalk exists between dietary restriction, mTOR, and IIS signaling pathway.

Nutrition-related signals activate the complexes TORC1 and TORC2 of the mTOR pathway. The activity of TORC1 is regulated by amino acids and growth factors (including insulin, ATP, and glycolytic metabolites). TORC2 is regulated by growth factor signals such as insulin and EGF, and IIS growth factor signals activate downstream TORC1 through the PI3K/Akt pathway. The mTOR pathway promotes cell growth and proliferation by inhibiting cell autophagy and stimulating protein synthesis. A restricted diet will activate AMP/ATP to stimulate downstream AMPK and inhibit the performance of TORC1. In addition, Sirtuins are activated through the AMP/ATP pathway to stimulate downstream AMPK expression, activate FOXO/HIF2a gene expression in cells, promote SOD2 activation, and inhibit ROS production. SIRT1 can activate PGC-1α, which regulates mitochondrial function and regulates the transcription of essential genes. ROS antioxidants such as SOD2 participate in the expression of autophagy, which activates cell autophagy and then mitochondrial autophagy, allowing cells to remove damaged or inappropriate mitochondria selectively. This path diagram shows that dietary restriction, mTOR, and IIS signaling pathways promote cell growth and proliferation by increasing intracellular protein synthesis, inhibiting cell apoptosis, and resisting ROS damage, thus achieving antiaging effects. The arrow indicates activation. The T bar indicates suppression.

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