Tardigrade Dsup extends <i>C. elegans</i> life span by impeding mitochondrial respiration and promoting oxidative stress resistance

Tardigrades survive extreme environments partly through the damage suppressor (Dsup) protein, which protects DNA from ionizing radiation and oxidative stress. Dsup is largely unstructured but binds nucleosomes to shield DNA from damage. To investigate its protective role in a whole organism, we expressed the <i>Ramazzottius varieornatus</i> Dsup gene in the nematode <i>Caenorhabditis elegans</i>. Transgenic worms tolerated x-ray exposure and oxidative stress without apparent toxicity and exhibited a notable extension of life span. This effect was independent of the canonical DAF-2/DAF-16 longevity pathway and mitochondrial dynamics. Instead, Dsup expression markedly reduced mitochondrial respiration, providing a plausible mechanism for enhanced oxidative stress resistance and extended longevity. Our findings demonstrate that Dsup can confer stress resistance and longevity benefits across species, highlighting a unique protective strategy with potential implications for understanding aging and developing stress-resilient organisms.