Extension of C. elegans lifespan using the ·NO-delivery dinitrosyl iron complexes

The ubiquitous and emerging physiology function of endogenous nitric oxide in vascular, myocardial, immune, and neuronal systems prompts chemists to develop a prodrug for the controlled delivery of ·NO in vivo and for the translational biomedical application. Inspired by the discovery of natural [Fe(NO) 2 ] motif, herein, we develop the synthetic dinitrosyl iron complexes (DNICs) [Fe 2 (μ-SR) 2 (NO) 4 ] ( 1 ) as a universal platform for the O 2 -triggered release of ·NO, for the regulation of ·NO-release kinetics (half-life = 0.6–27.4 h), and for the activation of physiological function of ·NO. Using C. elegans as a model organism, the ·NO-delivery DNIC 1 regulates IIS signaling pathway, AMPK signaling pathway, and mitochondrial function pathway to extend the lifespan and to delay the aging process based on the lifespan analysis, SA-βgal activity assay, and next-generation RNA sequencing analysis. This study unveils the anti-aging effect of ·NO and develops DNICs as a chemical biology probe for the continued discovery of unprecedented NO physiology. Graphical abstract