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. 2021 Sep 6;8:731356. doi: 10.3389/fnut.2021.731356

Figure 1.

Figure 1

The proposed mechanism of caloric restriction (CR) impacts frailty. CR may reduce the risk of frailty and associated adverse outcomes by activating the AMPK and SIRT1 pathways, inhibiting the IGF-1 and mTOR signaling and ferroptosis, and reducing the inflammation mediated by NF-KB pathways. CR-induced SIRT1 activation may upregulate AMPK and suppress NF-κB and mTOR activity. CR and metformin may attenuate ferroptosis by activating the AMPK pathway and improving frailty. AMPK, adenosine 5′-monophosphate (AMP)-activated protein kinase; CR, caloric restriction; CRMs, caloric restriction mimetics; FOXO, forkhead box O; IGF-1, insulin-like growth factor-1; mTOR, mammalian target of rapamycin; NF-κB, nuclear factor-κB; SIRT1, silent mating-type information regulation 2 homolog 1.