Evolutionarily-conserved FOXO-regulated OSER1 extends lifespan and healthspan

Molecular aging reflects the time-dependent accumulation of cellular damage and loss of essential cellular functions. FOXO transcription factors and their downstream targets play critical roles in the response to aging-associated cellular damage. Here, we identify and characterize a novel FOXO-regulated stress response gene, Oxidative Stress Responsive Serine-rich Protein 1 (OSER1), whose level of expression dramatically influences lifespan in Bombyx mori, Caenorhabditis elegans, and Drosophila. Overexpression of OSER1 also enhances resistance to oxidative stress, starvation, and heat shock, whereas depletion increases susceptibility to these stressors. In humans, common OSER1 genetic variants are associated with longevity. These data show that OSER1 modulates the oxidative stress response and suggest that OSER1 is a potent positive regulator of lifespan and healthspan in multiple species.