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

Juewon Kim1, Shuichi Shibuya2,3, Yusuke Ozawa4

  • 1Department of Physiology, Konkuk University College of Medicine, 27478, Chungju, Republic of Korea. juewon@kku.ac.kr.

Geroscience
|January 12, 2026
PubMed

Insights

Superoxide dismutase 1 (SOD1) deficiency accelerates aging and reproductive decline via ferroptosis-linked oxidative stress. Ginseng root extract (GR) shows promise in mitigating these aging effects across species.

Area of Science:

  • Gerontology
  • Oxidative Stress Biology
  • Reproductive Biology

Background:

  • Aging is characterized by accumulating oxidative stress, leading to tissue degeneration and reduced reproductive capacity.
  • Superoxide dismutase 1 (SOD1) plays a crucial role in managing oxidative stress.
  • Dysregulation of redox balance is implicated in aging processes.

Purpose of the Study:

  • To investigate the role of SOD1 deficiency in accelerating oxidative injury and reproductive aging.
  • To explore the protective effects of ginseng root extract (GR) against SOD1-deficiency-induced aging.
  • To elucidate the underlying mechanisms, particularly ferroptosis-linked redox imbalance.

Main Methods:

  • Comparative analysis of aged hairless Sod1 knockout mice and wild-type controls.
  • Studies in Caenorhabditis elegans (C. elegans) SOD1-deficient strains.
  • Assessment of oxidative stress markers (8-isoprostane, MDA, pentosidine, reactive oxygen species, glutathione, iron, lipid peroxidation).
  • Evaluation of reproductive parameters (reproductive span, progeny output, folliculogenesis, estrous cyclicity, ovarian morphology).
  • Intervention with ferroptosis inhibitors and GR supplementation.

Main Results:

  • Sod1 deficiency in mice led to increased oxidative stress markers, skin pathology, and reproductive aging.
  • SOD1-deficient C. elegans exhibited ferroptosis features, shortened reproductive span, and reduced progeny.
  • Ferroptosis inhibition or GR supplementation rescued reproductive decline in SOD1-deficient models.
  • GR treatment restored ovarian function and morphology in Sod1-deficient female mice.

Conclusions:

  • SOD1 loss is a significant driver of ferroptosis-associated oxidative stress and reproductive aging.
  • Ginseng root extract (GR) demonstrates potent protective effects against SOD1-deficiency-induced aging.
  • GR represents a promising therapeutic strategy targeting redox imbalance for age-related decline.
Keywords:
FerroptosisGinseng root extractOxidative stressReproductive agingSOD1 deficiency

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