Abstract Aging is accompanied by cumulative oxidative stress that promotes tissue degeneration and reproductive decline. Here, we show that deficiency of superoxide dismutase 1 (SOD1) accelerates oxidative injury and reproductive aging through a ferroptosis-linked redox imbalance, and that ginseng root extract (GR) confers protection across species. Aged hairless Sod1 ⁻ / ⁻ mice exhibited markedly elevated skin and plasma oxidative stress markers—including 8-isoprostane, malondialdehyde (MDA), and pentosidine—together with dermal cyst formation and atrophic pathology. Complementary studies in C . elegans revealed that SOD1-deficient strains displayed increased reactive oxygen species, depleted glutathione, and elevated iron and lipid peroxidation—canonical features of ferroptosis-associated oxidative stress. These redox alterations coincided with shortened reproductive span and reduced progeny output, both rescued by ferroptosis inhibition or GR supplementation. In female Sod1 ⁻ / ⁻ mice, GR restored folliculogenesis, normalized estrous cyclicity, and improved ovarian morphology. Collectively, these findings identify SOD1 loss as a driver of ferroptosis-associated oxidative and reproductive aging and highlight GR as a promising redox-targeted intervention.
Kim et al. (2026) studied this question.