NMN-SIRT1 signaling ameliorates IUGR via oxidative stress-mediated mitophagy to promote placental angiogenesis

Jie Peng; Yanlin Zhang; Kaiguo Gao; Shiqi Zheng; Wei Zhang; Ziying Li; Yanle He; Kai Yan; Yanhua Huang; Wei Wang; Junwen Wang; Chengquan Tan; Wan Dan; Rui Li; Yulong Yin; Yuanfei Zhou

doi:10.59717/j.xinn-life.2026.100201

The Innovation Life > 2026 Vol. 4 > No. 2 > 100201

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NMN-SIRT1 signaling ameliorates IUGR via oxidative stress-mediated mitophagy to promote placental angiogenesis

1.
College of Animal Science and Technology, Zhongkai University of Agriculture and Engineering, Guangzhou 510225, China
2.
Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha 410125, China
3.
State Key Laboratory of Swine and Poultry Breeding Industry, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China
4.
College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China
5.
College of Animal Science, South China Agricultural University, Guangzhou 510642, China
6.
Division of AOS & CDC, Faculty of Dentistry, and State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong SAR 999077, China
7.
National Center of Technology Innovation for Pigs, Chongqing 402460, China
8.
Frontiers Science Center for Animal Breeding and Sustainable Production, Wuhan 430070, China
9.
These authors contributed equally

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Corresponding authors: lirui181000@163.com (R.L.); yinyulong@isa.ac.cn (Y.Y.); zhouyuanfei@mail.hzau.edu.cn (Y.Z.)
Received Date: June 09, 2025

Accepted Date: December 15, 2025

Published Online: January 20, 2026

The Innovation Life 4(2), https://doi.org/10.59717/j.xinn-life.2026.100201 | Cite this article

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GRAPHICAL ABSTRACT

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PUBLIC SUMMARY

PUBLIC SUMMARY
1. Dietary NMN (2-5g/d) enhances placental angiogenesis and reduces IUGR incidence in sows.
  
  NMN upregulates placental SIRT1, alleviating oxidative stress in sows/offspring.
  
  NMN-SIRT1 axis inhibits excessive mitophagy and promotes angiogenesis in placenta.
  
  NMN-SIRT1 activation restores PVEC migration via oxidative stress/mitophagy regulation.
  
  Baseline NMN-SIRT1 signaling stimulates mitophagy to sustain PVEC angiogenic capacity.

ABSTRACT

ABSTRACT

Nicotinamide mononucleotide (NMN) is a natural anti-aging agent. However, its effects on intrauterine growth restriction (IUGR) remain insufficiently explored. This study found that daily intake of 2-5 g/d of NMN significantly enhanced placental angiogenesis and reduced the incidence of IUGR by using a pregnant sow model (Landrace × Yorkshire breed). Mechanistically, NMN upregulated SIRT1 expression in the placenta, alleviated oxidative stress in sows, placentas, and their offspring, inhibited excessive mitophagy in the placenta, and promoted angiogenesis. Furthermore, activation of the NMN-SIRT1 signaling pathway was observed to mitigate oxidative stress and mitophagy, thereby restoring the migratory capacity of porcine vascular endothelial cells (PVECs) and improving endothelial function. However, in the absence of oxidative stress, NMN-SIRT1 acts as a potent mitophagy-promoting signal, positively regulating PVEC angiogenesis. In conclusion, our study demonstrates that the activation of NMN-SIRT1 signaling is crucial for reducing adverse pregnancy outcomes by ameliorating placental dysfunction induced by perinatal oxidative stress.
- IUGR /
- NMN /
- Oxidative stress /
- Mitophagy /
- Angiogenesis

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Peng J., Zhang Y., Gao K., et al. (2026). NMN-SIRT1 signaling ameliorates IUGR via oxidative stress-mediated mitophagy to promote placental angiogenesis. The Innovation Life 4:100201. https://doi.org/10.59717/j.xinn-life.2026.100201

Peng J., Zhang Y., Gao K., et al. (2026). NMN-SIRT1 signaling ameliorates IUGR via oxidative stress-mediated mitophagy to promote placental angiogenesis. The Innovation Life 4:100201. https://doi.org/10.59717/j.xinn-life.2026.100201

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NMN-SIRT1 signaling ameliorates IUGR via oxidative stress-mediated mitophagy to promote placental angiogenesis

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NMN-SIRT1 signaling ameliorates IUGR via oxidative stress-mediated mitophagy to promote placental angiogenesis

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