A Melatonin-Catechol Hybrid Molecule Prolongs Lifespan via Regulating ROS and Reprogramming Mitochondrial Metabolism.

Chengyuan Qian, Yunhua Zhang, Xiaofeng Dang, Yating Shao, Chengyan Chu, Zijian Guo, Chen Xu, Xiaoyong Wang

State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, P. R. China. · pubmed

Paper

Abstract

Modulation of mitochondrial dynamics is a viable strategy for lifespan extension. Reactive oxygen species (ROS) play key roles in aging, acting either as signaling molecules to facilitate longevity-associated processes or as stimulators of oxidative stress, exerting deleterious effects on physiological functions. The hybrid molecule MC1 is designed by integrating melatonin and catechol moieties to reconstruct mitochondrial dynamics and selectively regulate the generation of ROS. MC1 combats cell senescence under oxidative stress and DNA damage, and reprograms the mitochondrial energy metabolism by inhibiting the tricarboxylic acid cycle and glycolysis, while initiating fatty acid oxidation to increase energy production. More importantly, MC1 significantly extends the lifespan of

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Research summary

The study claims that the hybrid molecule MC1 extends lifespan in model organisms by regulating reactive oxygen species and reprogramming mitochondrial metabolism. This represents an incremental advance in the field of geroprotectors, as it explores a known mechanism (mitochondrial modulation) with a novel chemical entity without demonstrating transformative efficacy or addressing fundamental longevity pathways beyond standard metabolic interventions.

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