Molecules and Cells

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Fig. 2.

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Fig. 2. Schematic models for combinatorial C. elegans and mammalian system studies regarding the role of insulin/IGF-1 signaling, mTOR pathway, and sirtuins. (A) DAF-16/forkhead box O (FOXO) is activated by genetic inhibition of EFL-1/E2F1 while being inhibited by mutations in ercc-1/Ercc1. Activated DAF-16/FOXO delays aging by increasing target gene expression. (B) Reduced mechanistic target of rapamycin (mTOR) signaling by genetic inhibition or treatment with rapamycin activates adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) via downregulating RSKS-1/S6K1 and upregulates SKN-1/Nrf to induce protective genes, leading to longevity. (C) Kallistatin downregulates miR-34a leading to the activation of SIR-2.1/SIRT1 to delay aging. Increased nicotinamide adenine dinucleotide (NAD+) levels also delay aging through upregulation of SIR-2.1/SIRT1.
Mol. Cells 2021;44:425~432
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