ACS Omega · Nov 13, 2026
Myo-Inositol Acts as a Multitarget Calorie Restriction Mimetic in Caenorhabditis elegans
By Chin CH, Zheng YX, Lin TT et al.
Calorie restriction (CR) is one of the most effective interventions for extending one’s lifespan; however, its long-term application is difficult to maintain, highlighting the need for calorie restriction mimetics (CRMs). Myo-inositol (MI) has previously been shown to promote longevity in Caenorhabditis (C.) elegans by suppressing the insulin/insulin-like growth factor signaling (IIS) pathway. To evaluate the CRM potential of MI, we investigated as to whether its longevity-promoting effects could be masked by dietary restriction (DR) and whether its underlying mechanisms resemble those of CR. MI significantly extended lifespan and improved health in C. elegans, and these effects were not additive under DR, supporting its potential as a CRM. Building on our previous finding that MI-induced longevity requires AKT-1, DAF-16, and DAF-18, loss-of-function mutation analyses further demonstrated that MI-induced longevity also depends on AAK-2, DAF-15, and ITR-1. Western blot analyses further showed that MI recapitulated key CR-associated molecular changes by increasing the p-AMPK/AMPK ratio and reducing mTOR expression in human Hs68 cells. Similar changes were observed in TOR- and AMPK-immunoreactive proteins in C. elegans. Both MI- and DR-induced longevity required ITR-1/Ca2+ signaling. Collectively, in addition to IIS pathway, these findings demonstrated that MI mimics CR through the coordinated regulation of multiple conserved signaling pathways, including AMPK, TOR, and ITR-1/Ca2+ signaling, highlighting its potential as a multitarget CRM.