@article{Yuan2026, 
author = {Chang Yuan and Junying Zhang and Wei Yao and Mingqin Qu and Lingqiang Zhang and Xiangming Wang and Minmin Liang},
title = {Bioengineered superoxide buffering extends lifespan via regulation of mitochondrial redox homeostasis and UPRmt activation},
year = {2026},
journal = {Nano Research},
volume = {19},
number = {1},
pages = {94908027},
keywords = {aging, redox homeostasis, lifespan extension, superoxide buffering, superoxide dismutase (SOD)},
url = {https://www.sciopen.com/article/10.26599/NR.2025.94908027},
doi = {10.26599/NR.2025.94908027},
abstract = {Redox homeostasis is crucial for cellular function, and its disruption is associated with numerous diseases and age-related pathologies. Superoxide (·O2−), a key reactive oxygen species (ROS), functions as a crucial signaling molecule under normal physiological processes; however, both its excessive accumulation and deficiency can lead to significant detrimental effects on organismal health. Inspired by the natural enzyme superoxide dismutase (SOD), which alleviates oxidative stress by neutralizing excess free radicals and modulates intracellular ROS levels to activate anti-aging pathways, we bioengineered a novel "superoxide buffering formulation" (SOD Buffer) to precisely regulate mitochondrial superoxide levels. Using C. elegans as a model, we show that SOD Buffer reduces superoxide accumulation under oxidative stress (e.g., UV exposure) and restores superoxide levels under its depletion (e.g., post-MitoQ treatment), without affecting general ROS level. Mechanistically, SOD Buffer modulates superoxide levels to activate the mitochondrial unfolded protein response (UPRmt), evidenced by the increased HSP-6 expression. This activation is mediated by the transcription regulators ATFS-1 and DVE-1, which govern mitochondrial stress responses. Functionally, SOD Buffer extends average lifespan by 36.98% and improves aging-related behaviors in C. elegans in a UPRmt dependent manner. These findings highlight the therapeutic promise of targeted superoxide modulation to maintain mitochondrial health and promote longevity.}
}