# SOD1 deficiency drives ferroptosis-linked oxidative and reproductive aging, mitigated by ginseng root extract

## TL;DR

This study shows that SOD1 deficiency causes oxidative stress and reproductive aging through ferroptosis, and ginseng root extract can help reverse these effects.

## Contribution

The study identifies SOD1 loss as a driver of ferroptosis-linked aging and introduces ginseng root extract as a potential intervention.

## Key findings

- SOD1 deficiency increases oxidative stress markers and causes skin and reproductive aging in mice.
- Ginseng root extract rescues reproductive function and reduces oxidative damage in SOD1-deficient models.
- Ferroptosis inhibition or GR supplementation reverses redox imbalance and reproductive decline in C. elegans and mice.

## 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.

The online version contains supplementary material available at 10.1007/s11357-025-02093-8.